John Garner's Technical Blog
John GarnerJohn Garner, Manager

What's New and on the Manager's Mind

A blog dedicated to answering technical questions in an open format relating to products from PolySciTech, a division of Akina, Inc.


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Memorial Day

Sunday, May 27, 2018, 7:39 AM ET

Akina, Inc. (www.akinainc.com) Will be closed for Memorial Day May 28, 2018. We will resume normal business the following day.

BPCR Free Scientific Networking Conference August 29, 2018

Monday, May 21, 2018, 3:13 PM ET

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. This conference focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. Speakers include Anton Iliuk (Tymora), Kelvin Okamoto (Gen3Bio), Cedric D’Hue (D’Hue Law), and Raouf Gharbo (Peerbridge Health). Free exhibit-hall booth spaces still available. (BPCRconference.com)

PLGA-amine and PEG-PLGA from PolySciTech used in development of micro-RNA based treatment for glioblastoma

Monday, May 14, 2018, 7:45 PM ET

As DNA is transcribed it proceeds through an RNA (single strand) precursor which is then used to synthesize proteins. One therapeutic strategy is to find RNA counter-sequences which block the transcription for proteins of certain types (i.e. cancer-related factors) as this can reduce the growth and spread of cancer. Recently, researchers at Stanford University used PLGA-NH2 (AI010) and mPEG-PLGA (AK071) from PolySciTech (www.polyscitech) to develop novel brain-cancer therapy. This research holds promise for development of therapeutic strategies against this often fatal form of cancer. Read more: Meenakshi Malhotra, Thillai Veerapazham Sekar, Jeyarama S. Ananta, Rammohan Devulapally, Rayhaneh Afjei, Husam A. Babikir, Ramasamy Paulmurugan, and Tarik F. Massoud “Targeted nanoparticle delivery of therapeutic antisense microRNAs presensitizes glioblastoma cells to lower effective doses of temozolomide in vitro and in a mouse model” Oncotarget. 2018; 9:21478-21494. https://doi.org/10.18632/oncotarget.25135

“ABSTRACT: Temozolomide (TMZ) chemotherapy for glioblastoma (GBM) is generally well tolerated at standard doses but it can cause side effects. GBMs overexpress microRNA-21 and microRNA-10b, two known oncomiRs that promote cancer development, progression and resistance to drug treatment. We hypothesized that systemic injection of antisense microRNAs (antagomiR-21 and antagomiR-10b) encapsulated in cRGD-tagged PEG-PLGA nanoparticles would result in high cellular delivery of intact functional antagomiRs, with consequent efficient therapeutic response and increased sensitivity of GBM cells to lower doses of TMZ. We synthesized both targeted and non-targeted nanoparticles, and characterized them for size, surface charge and encapsulation efficiency of antagomiRs. When using targeted nanoparticles in U87MG and Ln229 GBM cells, we showed higher uptake-associated improvement in sensitivity of these cells to lower concentrations of TMZ in medium. Co-inhibition of microRNA-21 and microRNA-10b reduced the number of viable cells and increased cell cycle arrest at G2/M phase upon TMZ treatment. We found a significant increase in expression of key target genes for microRNA-21 and microRNA-10b upon using targeted versus non-targeted nanoparticles. There was also significant reduction in tumor volume when using TMZ after pre-treatment with loaded nanoparticles in human GBM cell xenografts in mice. In vivo targeted nanoparticles plus different doses of TMZ showed a significant therapeutic response even at the lowest dose of TMZ, indicating that preloading cells with antagomiR-21 and antagomiR-10b increases cellular chemosensitivity towards lower TMZ doses. Future clinical applications of this combination therapy may result in improved GBM response by using lower doses of TMZ and reducing nonspecific treatment side effects.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. See more BPCRconference.com

PLLA from PolySciTech used in development of biodegradable vascular graft

Monday, May 14, 2018, 7:43 PM ET

Heart disease is one of the major causes of mortality worldwide. Biodegradable synthetic grafts can be used to improve healing of blocked or damaged vessels. Recently, researchers from Universitas Airlangga (Indonesia) used PLLA (Cat# AP006) from PolySciTech (www.polyscitech.com) to generate a biodegrdable graft. This research holds promise for providing for treatment of cardiovascular disease. Read more: Iffa A. Fiqrianti, Prihartini Widiyanti, Muhammad A. Manaf, Claudia Y. Savira, Nadia R. Cahyani, and Fitria R. Bella “Poly-L-lactic Acid (PLLA)-Chitosan-Collagen Electrospun Tube for Vascular Graft Application” Journal of Functional Biomaterials 2018, 9, 32; doi:10.3390/jfb9020032 (http://www.mdpi.com/2079-4983/9/2/32)

“Abstract: Poly-L-Lactic acid (PLLA) blended with chitosan and collagen was used to fabricate a conduit for blood vessel engineering through an electrospinning process. Various concentrations of chitosan were used in the blend in order to study its effect on the morphology, chemical bond, tensile strength, burst pressure, hemocompatibility, and cell viability (cytotoxicity) of the tube. In vitro assessments indicated that addition of chitosan-collagen could improve cell viability and hemocompatibility. Best results were demonstrated by the conduit with 10% PLLA, 0.5% chitosan, and 1% collagen. Tensile strength reached 2.13 MPa and burst pressure reached 2593 mmHg, both values that are within the range value of native blood vessel. A hemolysis percentage of 1.04% and a cell viability of 86.2% were obtained, meeting the standards of high hemocompatibility and low cytotoxicity for vascular graft material. The results are promising for further development toward vascular graft application. Keywords: poly L-lactic acid; collagen; chitosan; electrospinning; tube; vascular graft”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. See more BPCRconference.com

PEG-PLA from PolySciTech used to develop silver-antibiotic nanoparticle for treatment of MRSA

Monday, May 14, 2018, 3:03 PM ET

For decades, antibiotics have been the ‘go-to’ therapy for a broad range of diseases. In many ways, it has been the development of antibiotics which has allowed society to grow to where it is now. In the absence of these interventions, diseases such as cholera and typhoid would have wiped out large numbers of people. Bacteria, like all living organisms, are adaptive and as time goes by, more and more bacteria are presenting resistance against antibiotics which drastically limits treatment options. Notably, MRSA, remains resistant to most available treatment options and can be deadly. Recently, researchers at Northeastern University used mPEG-PLA (AK021) from PolySciTech (www.polyscitech.com) to develop nanoparticles loaded with silver, gentamicin, and fructose. They found these agents work together to kill MRSA in a synergistic manner. This research holds promise to provide vital treatment options for this nearly incurable disease. Read more: Gelfat, Ilia, Benjamin M. Geilich, and Thomas J. Webster. "Fructose-Enhanced Antimicrobial Activity of Silver Nanoparticle-Embedded Polymersome Nanocarriers." Journal of biomedical nanotechnology 14, no. 3 (2018): 619-626. https://www.ingentaconnect.com/contentone/asp/jbn/2018/00000014/00000003/art00017?crawler=true&mimetype=application/pdf

“Abstract: In recent years, an increasing body of research has indicated that the antimicrobial activity of certain antibiotic drugs can be enhanced by the addition of specific metabolites. This study aimed to incorporate these findings into polymersomes (novel polymer-based nanoscale drug delivery vehicles) which can be loaded with various therapeutic molecules and nanoparticles. Polymersome technology has shown promising results in treating antibiotic-resistant infections by co-encapsulating the antibiotic methicillin with silver nanoparticles. Here, silver nanoparticle-embedded polymersomes (AgPs) were synthesized in a similar fashion with gentamicin replacing methicillin as the antibiotic agent and supplemented with fructose to promote efficacy. Two clinically-isolated strains of methicillin-resistant Staphylococcus aureus (MRSA) (ATCC #43300 and ATCC #25923) were cultured and treated with the new AgP formulations, with the former strain being susceptible to gentamicin and the latter strain being resistant to gentamicin. The treatment of the non-resistant strain yielded promising results with the polymersomes without fructose supplementation inducing a maximal growth rate reduction of up to 40% and an increase in lag time of up to 141% relative to the untreated control. Impressively, the fructose-loaded polymersomes completely eliminated the bacterial growth over the observed time period at the higher doses and outperformed the no-fructose treatment at all concentrations. However, despite significantly reducing bacterial growth, the treatment of the gentamicin-resistant strain did not seem to be enhanced by the addition of fructose. Lastly, the present study demonstrated that the presence of fructose in the polymersomes seemed to slightly ameliorate the cytotoxic effect of the treatment on human dermal fibroblasts (a model mammalian cell). In addition to developing and testing a new polymersome formulation with fructose resulting in increased efficacy, the results of this study also demonstrated the variability inherent to developing novel antimicrobial treatments for different bacterial strains.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. See more BPCRconference.com

Chitosan derivatives from PolySciTech used in the investigation of cuticle interactions to develop advanced materials

Wednesday, May 9, 2018, 3:22 PM ET

There still remains a great deal to learn about how natural materials are structured and how the various components interact. There is a great opportunity for taking lessons how things in nature are constructed and applying that understanding to man-made technologies to improve these designs. A great example is spider silk which, relative to its weight, is one of the strongest substances in nature and a great deal stronger than most man-made materials. Developing this requires an understanding of how the natural material is constructed and how the various components work together. Recently, researchers from the University of Kansas and Kansas State University used low molecular weight and FITC-labelled Chitosan (Kitopure) from PolySciTech (www.polyscitech.com) to investigate the interactions amongst biomacromolecules within insect cuticle. This research holds promise for enabling the generation of advanced biomimetic materials. Read more: Vaclaw, M. Coleman, Patricia A. Sprouse, Neal T. Dittmer, Saba Ghazvini, C. Russell Middaugh, Michael R. Kanost, Stevin H. Gehrke, and Prajnaparamita Dhar. "Self-assembled coacervates of chitosan and an insect cuticle protein containing a Rebers-Riddiford motif." Biomacromolecules (2018). https://pubs.acs.org/doi/abs/10.1021/acs.biomac.7b01637

“The interactions among biomacromolecules within insect cuticle may offer new motifs for biomimetic material design. CPR27 is an abundant protein in the rigid cuticle of the elytron from Tribolium castaneum. CPR27 contains the Rebers–Riddiford (RR) motif, which is hypothesized to bind chitin. In this study, active magnetic microrheology coupled with microscopy and protein particle analysis techniques were used to correlate alterations in the viscosity of chitosan solutions with changes in solution microstructure. Addition of CPR27 to chitosan solutions led to a 3-fold drop in viscosity. This change was accompanied by the presence of micrometer-sized coacervate particles in solution. Coacervate formation had a strong dependence on chitosan concentration. Analysis showed the existence of a critical CPR27 concentration beyond which a significant increase in particle count was observed. These effects were not observed when a non-RR cuticular protein, CP30, was tested, providing evidence of a structure–function relationship related to the RR motif.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. See more BPCRconference.com

PLGA from PolySciTech used in the development of Genipin-eluting sutures for tendon repair

Wednesday, May 9, 2018, 3:21 PM ET

Repairing mechanically-stressed tissues, such as tendons, creates a challenging situation in the orthopedic surgical field. Conventionally, sutures work poorly for this application as the strength requirements for holding the tendon in place are very high and the interface between the suture and the tendon creates a weak point which is prone to failure. Genipin is a naturally-derived crosslinking material which can act to potentially reinforce tissues. Recently, researchers from Balgrist University and ETH Zurich (Switzerland) used PLGA (PolyVivo AP081) from PolySciTech (www.polyscitech.com) to develop and test sutures loaded with Genipin for tendon repair. This research holds promise to improve orthopedic surgical outcomes and healing for tendon-repair procedures. Read more: Camenzind, Roland S., Timo O. Tondelli, Tobias Goetschi, Claude Holenstein, and Jess G. Snedeker. "Can Genipin-coated Sutures Deliver a Collagen Crosslinking Agent to Improve Suture Pullout in Degenerated Tendon? An Ex Vivo Animal Study." Clinical Orthopaedics and Related Research 476, no. 5 (2018): 1104-1113. https://journals.lww.com/clinorthop/Fulltext/2018/05000/Can_Genipin_coated_Sutures_Deliver_a_Collagen.34.aspx

“Background The suture-tendon interface is often the weakest link in tendon-to-tendon or tendon-to-bone repair. Genipin is an exogenous collagen crosslink agent derived from the gardenia fruit that can enhance suture force to failure of the tendon-suture interface. Viable methods for intraoperative clinical delivery of genipin could be of clinical utility, but to our knowledge have not yet been extensively studied. Questions/purposes The purposes of this study were (1) to evaluate whether sutures precoated with genipin can augment the suture-tendon interface to improve force to failure, stiffness, and work to failure in healthy and degenerated tendons; and (2) to determine the effect of genipin on the extent and distribution of crosslinking. Methods Single-stitch suture pullout tests were performed ex vivo on 25 bovine superficial digital flexor tendons. To assess effects on native tissue, one group of 12 tendons was cut in proximal and distal halves and randomized to treatment (n = 12) and control groups (n = 12) in a matched-pair design. One simple stitch with a loop with either a normal suture or genipin-coated suture was applied to tendons in both groups. To simulate a degenerative tendon condition, a second group of 13 tendons was cut in proximal and distal halves, injected with 0.2 mL of collagenase D (8 mg/mL) and incubated for 24 hours before suturing with either a genipin-coated suture (n = 13) or their matched controls (n = 13). Sutures from all groups then were loaded to failure on a universal materials testing machine 24 hours after suturing. Suture pullout force, stiffness, and work to failure were calculated from force-displacement data and compared between the groups. Additionally, fluorescence was measured to determine the degree of crosslinking quantitatively and a qualitative analysis of the distribution pattern was performed by microscopy. Results In healthy tendon pairs, the median maximum pullout force was greater with genipin-coated sutures than with control sutures (median, 42 N [range, 24–73 N] versus 29 N [range, 13–48 N]; difference of medians, 13 N; p = 0.003) with corresponding increases in the required work to failure (median, 275 mJ [range, 48–369 mJ] versus 148 mJ [range, 83–369 mJ]; difference of medians, 127 mJ; p = 0.025) but not stiffness (median, 4.1 N/mm [range, 2.3–8.1 N/mm] versus 3.3 N/mm [range, 1.1–9.6 N/mm]; difference of medians, 0.8 N/mm; p = 0.052). In degenerated tendons, median maximum pullout force was greater with genipin-coated sutures than with control sutures (median, 16 N [range, 9-36 N] versus 13 N [range, 5-28 N]; difference of medians, 3 N; p = 0.034) with no differences in work to failure (median, 75 mJ [range, 11–249 mJ] versus 53 mJ [range, 14–143 mJ]; difference of medians, 22 mJ; p = 0.636) or stiffness (median, 1.9 N/mm [range, 0.7–13.4 N/mm] versus 1.6 N/mm [range, 0.5–5.6 N/mm]; difference of medians, 0.3 N/mm; p = 0.285). Fluorescence was higher in tendons treated with genipin-coated sutures compared with the control group, whereas higher fluorescence was observed in the treated healthy compared with the degenerated tendons (difference of means -3.16; standard error 1.08; 95% confidence interval [CI], 0.97–5.34; p = 0.006/healthy genipin: mean 13.04; standard error 0.78; 95% CI, 11.47-14.62; p < 0.001/degenerated genipin: mean 9.88; SD 0.75; 95% CI, 8.34-11.40; p < 0.001). Conclusions Genipin-coated sutures improved force to failure of a simple stitch at the tendon-suture interface in healthy and degenerated tendons in an ex vivo animal model. Fluorescence was higher in tendons treated with genipin-coated sutures compared with the control group. Clinical Relevance A genipin-coated suture represents a potential delivery vehicle for exogenous crosslink agents to augment suture retention properties. In vivo animal studies are the next logical step to assess safety and efficacy of the approach.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. See more BPCRconference.com

Mal-Peg-PLGA from PolySciTech used in development of combination immunotherapy for cancer treatment.

Saturday, May 5, 2018, 10:33 PM ET

One of the more promising methods to treat cancer is the application of immunotherapy. Simply put, this is training the human immune system to attack the cancerous cells as though they were pathogens. There are significant advantages to this technique over other methods that rely on an external agent which kills the cancer cells in that the immune system can attack the cancer throughout the body without damaging normal cells. Recently, researchers at University of North Carolina at Chapel Hill used Mal-PEG-PLGA (PolyVivo AI110) and mPEG-PLGA (AK029) from PolySciTech (www.polyscitech.com) to generate immunotherapy nanoparticles for cancer treatment. This research holds promise to provide for improved therapies against cancer. Read more: Mi, Yu, Christof C. Smith, Feifei Yang, Yanfei Qi, Kyle C. Roche, Jonathan S. Serody, Benjamin G. Vincent, and Andrew Z. Wang. "A Dual Immunotherapy Nanoparticle Improves TCell Activation and Cancer Immunotherapy." Advanced Materials (2018): 1706098. https://onlinelibrary.wiley.com/doi/abs/10.1002/adma.201706098

“Abstract: Combination immunotherapy has recently emerged as a powerful cancer treatment strategy. A promising treatment approach utilizes coadministration of antagonistic antibodies to block checkpoint inhibitor receptors, such as antiprogrammed cell death1 (aPD1), alongside agonistic antibodies to activate costimulatory receptors, such as antitumor necrosis factor receptor superfamily member 4 (aOX40). Optimal Tcell activation is achieved when both immunomodulatory agents simultaneously engage Tcells and promote synergistic proactivation signaling. However, standard administration of these therapeutics as free antibodies results in suboptimal Tcell binding events, with only a subset of the Tcells binding to both aPD1 and aOX40. Here, it is shown that precise spatiotemporal codelivery of aPD1 and aOX40 using nanoparticles (NP) (dual immunotherapy nanoparticles, DINP) results in improved Tcell activation, enhanced therapeutic efficacy, and increased immunological memory. It is demonstrated that DINP elicits higher rates of Tcell activation in vitro than free antibodies. Importantly, it is demonstrated in two tumor models that combination immunotherapy administered in the form of DINP is more effective than the same regimen administered as free antibodies. This work demonstrates a novel strategy to improve combination immunotherapy using nanotechnology.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. See more BPCRconference.com


Thermogelling polymers from Akina, Inc. used in development of controlled medicinal release in the eye

Tuesday, May 1, 2018, 9:15 PM ET

After surgery, several complications can occur as the human body is susceptible to infections, inflammatory response, and swelling. This is especially true in ocular surgery due to the relatively delicate structure of the eye. There are several medications which are effective at preventing infection (antibiotics), inflammation (steroids), and ocular over-pressure (hypotensives). However, each of these medicines is administered repeatedly through eye-drops. Eye-drops typically work poorly as the medicine is flushed away by tears and patients tend to forget to use them. A better solution to ensure appropriate application of medicine is to apply timed-release using a thermogel encapsulating microparticles to ensure each drug gets released at the appropriate times. Recently, researchers at University of Michigan, Johns Hopkins University, and Howard University, used several polymers including PLGA-PEG-PLGA (Polyvivo AK012, AK091), PLA-PEG-PLA (Polyvivo AK100), PLCL-PEG-PLCL (Polyvivo AK108, AK109) as well as PLGA (Polyvivo AP043, AP018, and AP087) from PolySciTech (www.polyscitech.com) to generate microparticle loaded thermogels for controlled delivery of multiple therapeutic agents. This research holds promise to improve the outcomes from ocular surgery by preventing inflammation, infection and swelling. Read more: Mohammadi, Maziar, Kisha Patel, Seyedeh P. Alaie, Ron B. Shmueli, Cagri G. Besirli, Ronald G. Larson, and Jordan J. Green. "Injectable drug depot engineered to release multiple ophthalmic therapeutic agents with precise time profiles for postoperative treatment following ocular surgery." Acta biomaterialia (2018). https://www.sciencedirect.com/science/article/pii/S174270611830240X

“Abstract: A multi-drug delivery platform is developed to address current shortcomings of post-operative ocular drug delivery. The sustained biodegradable drug release system is composed of biodegradable polymeric microparticles (MPs) incorporated into a bulk biodegradable hydrogel made from triblock copolymers with poly(ethylene glycol) (PEG) center blocks and hydrophobic biodegradable polyester blocks such as poly(lactide-co-glycolide) (PLGA), Poly(lactic acid) (PLA), or Poly(lactide-co-caprolactone) (PLCL) blocks. This system is engineered to flow as a liquid solution at room temperature for facile injection into the eye and then quickly gel as it warms to physiological body temperatures (approximately 37 °C). The hydrogel acts as an ocular depot that can release three different drug molecules at programmed rates and times to provide optimal release of each species. In this manuscript, the hydrogel is configured to release a broad-spectrum antibiotic, a potent corticosteroid, and an ocular hypotensive, three ophthalmic therapeutic agents that are essential for post-operative management after ocular surgery, each drug released at its own timescale. The delivery platform is designed to mimic current topical application of postoperative ocular formulations, releasing the antibiotic for up to a week, and the corticosteroid and the ocular hypotensive agents for at least a month. Hydrophobic blocks, such as PLCL, were utilized to prolong the release duration of the biomolecules. This system also enables customization by being able to vary the initial drug loading to linearly tune the drug dose released, while maintaining a constant drug release profile over time. This minimally invasive biodegradable multi-drug delivery system is capable of replacing a complex ocular treatment regimen with a simple injection. Such a depot system has the potential to increase patient medication compliance and reduce both the immediate and late term complications following ophthalmic surgery. Statement of Significance: After ocular surgery, patients routinely receive multiple medications including antibiotics, steroids and ocular hypotensives to ensure optimal surgical outcomes. The current standard of care for postoperative treatment after ocular surgery involves using eye drops daily, which has limited effectiveness mainly due to poor patient adherence. To improve patient experience and outcomes, this article presents the first thermoresponsive hydrogel able to release multiple drug molecules for the application of post-operative treatment following ocular surgery. By varying the parameters such as hydrogel type and polymer hydrophobicity, the drug release profile, duration and dosage can finely be tuned. The approach presented in this article can readily be applied to other applications by simply changing the drug loaded in the drug delivery system.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

PLGA-Rhodamine from PolySciTech used in development of nanoparticles to kill bacteria that hide inside of human cells

Tuesday, May 1, 2018, 9:14 PM ET

Klebsiella pneumoniae is a particularly nasty bacterial strain that can survive being swallowed by a cell and is resistant to traditional antibiotics in this state as the cell protects it from these medicines. This bacteria leads to severe lung infections and can be deadly. Recently, researchers at Queen’s University Belfast used PLGA-Rhodamine (PolyVivo AV011) from PolySciTech (www.polyscitech.com) to generate fluorescent-traceable nanoparticles. They tracked the uptake of gentamicin-loaded nanoparticles into cells as a means to treat intra-cellular bacteria. This research holds promise to provide for treatment against this antibiotic-resistant disease. Read more: Jiang, Lai, Michelle K. Greene, Jose Luis Insua, Joana Sa Pessoa, Donna M. Small, Peter Smyth, Aidan McCann et al. "Clearance of intracellular Klebsiella pneumoniae infection using gentamicin-loaded nanoparticles." Journal of Controlled Release (2018). https://www.sciencedirect.com/science/article/pii/S0168365918302244

“Abstract: Klebsiella pneumoniae is a foremost gram-negative pathogen that can induce life-threatening nosocomial pulmonary infections. Although it can be phagocytosed successfully by lung resident macrophages, this pathogen remains viable within vacuolar compartments, resulting in chronic infection and limiting therapeutic treatment with antibiotics. In this study, we aimed to generate and evaluate a cell-penetrant antibiotic poly(lactide-co-glycolide) (PLGA)-based formulation that could successfully treat intracellular K. pneumoniae infection. Screening of formulation conditions allowed the generation of high drug entrapment nanoparticles through a water-in-oil-in-water approach. We demonstrated the therapeutic usefulness of these gentamicin-loaded nanoparticles (GNPs), showing their ability to improve survival and provide extended prophylactic protection towards K. pneumoniae using a Galleria mellonella infection model. We subsequently showed that the GNPs could be phagocytosed by K. pneumoniae infected macrophages, and significantly reduce the viability of the intracellular bacteria without further stimulation of pro-inflammatory or pro-apoptotic effects on the macrophages. Taken together, these results clearly show the potential to use antibiotic loaded NPs to treat intracellular K. pneumoniae infection, reducing bacterial viability without concomitant stimulation of inflammatory or pyroptotic pathways in the treated cells. Keywords: Gentamicin; PLGA; Nanoparticles; Klebsiella pneumoniae; Intracellular infection; Macrophage; Inflammation; Pyroptosis”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

PLGA from PolySciTech used in development of 3D printed cartilage scaffold for tissue engineering

Tuesday, May 1, 2018, 9:12 PM ET

Tissue engineering is a process by which cells and cell-growth scaffolds are emplaced in a patient where there is damage to the native tissue. Cells must have a surface to grow on so one of the most critical components of any tissue engineering system is a substrate/structure which the cells can grow on and interact with for successfully replacing the original tissue. This is not a trivial process, as most tissues are not uniform and so the interaction between the cells and the substrate is critical. Recently, researchers at the University of Maryland used PLGA (PolyVivo AP024) from PolySciTech (www.polyscitech.com) to generate 3D printed scaffolds and tested these for their cell-interaction capabilities as well as their ability to grow heterogenous tissues. This research holds promise for improving the development of tissue scaffolds to treat a wide range of injuries and disease states. Read more: Guo, Ting, Julia P. Ringel, Casey G. Lim, Laura G. Bracaglia, Maeesha Noshin, Hannah B. Baker, Douglas A. Powell, and John P. Fisher. "3D Extrusion Printing Induces Polymer Molecule Alignment and Cell Organization within Engineered Cartilage." Journal of Biomedical Materials Research Part A (2018). https://onlinelibrary.wiley.com/doi/abs/10.1002/jbm.a.36426

“Abstract: Proper cell–material interactions are critical to remain cell function and thus successful tissue regeneration. Many fabrication processes have been developed to create microenvironments to control cell attachment and organization on a threedimensional (3D) scaffold. However, these approaches often involve heavy engineering and only the surface layer can be patterned. We found that 3D extrusion based printing at high temperature and pressure will result an aligned effect on the polymer molecules, and this molecular arrangement will further induce the cell alignment and different differentiation capacities. In particular, articular cartilage tissue is known to have zonal collagen fiber and cell orientation to support different functions, where collagen fibers and chondrocytes align parallel, randomly, and perpendicular, respectively, to the surface of the joint. Therefore, cell alignment was evaluated in a cartilage model in this study. We used small angle Xray scattering analysis to substantiate the polymer molecule alignment phenomenon. The cellular response was evaluated both in vitro and in vivo. Seeded mesenchymal stem cells (MSCs) showed different morphology and orientation on scaffolds, as a combined result of polymer molecule alignment and printed scaffold patterns. Gene expression results showed improved superficial zonal chondrogenic marker expression in parallelaligned group. The cell alignment was successfully maintained in the animal model after 7 days with distinct MSC morphology between the casted and parallel printed scaffolds. This 3D printing induced polymer and cell alignment will have a significant impact on developing scaffold with controlled cell–material interactions for complex tissue engineering while avoiding complicated surface treatment, and therefore provides new concept for effective tissue repairing in future clinical applications.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

PLGA from PolySciTech used in development of bone-tissue scaffold to treat critical-size defect wounds

Tuesday, May 1, 2018, 9:10 PM ET

The ‘critical defect’ refers to a size (e.g. diameter of hole) of missing bone tissue beyond which the bone will not regrow. In situations of traumatic injury, damaging bone beyond this size can make healing impossible unless tissue engineering is applied. Recently, researchers at University of Pittsburgh and Southwest Jiaotong University (China) used PLGA (PolyVivo AP020) from PolySciTech (www.polyscitech.com) to create PLGA-Mg scaffolds for bone-tissue repair. This research holds promise for treating traumatic wounds. Read more: Chen, Yingqi, SangHo Ye, Hideyoshi Sato, Yang Zhu, Vesselin Shanov, Tarannum Tiasha, Antonio D’Amore, Samuel Luketich, Guojiang Wan, and William R. Wagner. "Hybrid scaffolds of Mg alloy mesh reinforced polymer/extracellular matrix composite for criticalsized calvarial defect reconstruction." Journal of tissue engineering and regenerative medicine (2018). https://onlinelibrary.wiley.com/doi/abs/10.1002/term.2668

“Abstract: The challenge of developing scaffolds to reconstruct criticalsized calvarial defects without the addition of high levels of exogenous growth factor remains relevant. Both osteogenic regenerative efficacy as well as suitable mechanical properties for the temporary scaffold system are of importance. In this study, a Mg alloy mesh reinforced polymer/demineralized bone matrix (DBM) hybrid scaffold was designed where the hybrid scaffold was fabricated by a concurrent electrospinning/electrospraying of poly(lacticcoglycolic) (PLGA) polymer and DBM suspended in hyaluronic acid (HA). The Mg alloy mesh significantly increased the flexural strength and modulus of PLGA/DBM hybrid scaffold. In vitro results demonstrated that the Mg alloy mesh reinforced PLGA/DBM hybrid scaffold (MgPLGA@HA&DBM) exhibited a stronger ability to promote the proliferation of bone marrow stem cells (BMSCs) and induce BMSC osteogenic differentiation compared to control scaffolding materials lacking critical components. In vivo osteogenesis studies were performed in a rat criticalsized calvarial defect model and incorporated a variety of histological stains and immunohistochemical staining of osteocalcin. At 12 weeks, the rat model data showed that the degree of bone repair for the MgPLGA@HA&DBM scaffold was significantly greater than for those scaffolds lacking one or more of the principal components. While complete defect filling was not achieved, the improved mechanical properties, promotion of BMSC proliferation and induction of BMSC osteogenic differentiation, and improved promotion of bone repair in the rat criticalsized calvarial defect model make Mg alloy mesh reinforced PLGA/DBM hybrid scaffold an attractive option for the repair of criticalsized bone defects where the addition of exogenous isolated growth factors is not employed.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

mPEG-PLGA from PolySciTech used in development of anti-viral loaded semen-responsive nanofibers to prevent the spread of HIV

Tuesday, May 1, 2018, 9:08 PM ET

HIV and other sexual diseases remain incurable and are increasing in prevalence as they spread through sexual interaction. Griffithsin, an antiviral agent, has promise to prevent the spread of these, but is short-acting and susceptible to break down. Recently, researchers at the University of Louisville used mPEG-PLGA (PolyVivo AK026) from PolySciTech (www.polyscitech.com) to develop nanofibers which release Griffithsin when the vaginal pH increases in the presence of semen. This research holds promise to provide for preventing the spread of HIV and other sexually transmitted diseases. Tyo, Kevin M., Jinghua Duan, Pravallika Kollipara, Mark Vincent C. dela Cerna, Donghan Lee, Kenneth E. Palmer, and Jill M. Steinbach-Rankins. "pH-Responsive delivery of Griffithsin from electrospun fibers." European Journal of Pharmaceutics and Biopharmaceutics (2018). https://www.sciencedirect.com/science/article/pii/S093964111830198X

“Abstract: Human immunodeficiency virus (HIV-1) affects over 36 million people globally. Current prevention strategies utilize antiretrovirals that have demonstrated protection, but result in antiviral resistance, adverse toxicity, and require frequent administration. A novel biologic, griffithsin (GRFT), has demonstrated outstanding safety and efficacy against laboratory and primary HIV isolates and against intravaginal murine herpes simplex virus 2 (HSV-2) challenge, making it a promising microbicide candidate. However, transient activity and instability remain concerns surrounding biologic delivery, particularly in the harsh environment of the female reproductive tract (FRT). Recently, electrospun fibers (EFs) have demonstrated promise for intravaginal delivery, with the potential to conserve active agent until release is needed. The goal of this study was to fabricate and characterize pH-responsive fibers comprised of poly(lactic-co-glycolic acid) (PLGA) or methoxypolyethylene glycol-b-PLGA (mPEG-PLGA) with varying ratios of poly(n-butyl acrylate-co-acrylic acid) (PBA-co-PAA), to selectively release GRFT under pH-conditions that mimic semen introduction. Fibers comprised of mPEG-PLGA:PBA-co-PAA (90:10 w/w) demonstrated high GRFT loading that was maintained within simulated vaginal fluid (SVF), and pH-dependent release upon exposure to buffered and SVF:simulated semen solutions. Moreover, GRFT fibers demonstrated potent in vitro efficacy against HIV-1 and safety in vaginal epithelial cells, suggesting their future potential for efficacious biologic delivery to the FRT. Keywords: Griffithsin (GRFT)Electrospun fiber Microbicide Protein delivery Sexually transmitted infection (STI)Human immunodeficiency virus (HIV)pH-responsive Female reproductive”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com


Polymers University Lesson 105: "Thermogels" live now

Friday, April 27, 2018, 9:50 AM ET

Akina Hosting Free Scientific-Networking Conference at Purdue Research Park August 29th

Wednesday, April 25, 2018, 4:28 PM ET

Science is more than simply performing research in a lab. The challenges of the 21st century require collaboration and cooperation not only between multiple labs but also between academia, entrepreneurs, and corporate scientists to provide solutions to complex problems. This requires networking and awareness which allow innovations to become available within the marketplace where they can flourish and improve people’s lives. In the Lafayette area, Purdue Research Park (the largest University-affiliated business complex in the country) has been growing by leaps and bounds with university spin-off technologies, start-ups, and small-business’s forming at a rapid pace. Despite this, there is relatively little awareness between the companies as to what products/services they provide or research applications they are working on. For this reason, Akina, Inc. is hosting a scientific networking conference. The BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN, BPCRconference.com) which is a free, 1-day scientific networking conference that focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields.

mPEG-PLGA from PolySciTech used in development of advanced AFM-IR nanoparticle characterization techniques

Wednesday, April 18, 2018, 9:21 PM ET

The best thing about nanotechnology is that it is small. The worst thing about nanotechnology is that it is small… very small… smaller than what a standard light microscope can typically observe. Naturally, obtaining meaningful information about the structure and morphology of nanoparticles is very difficult and requires advanced equipment and analysis techniques. Recently, researchers at University of Sydney (Australia) used mPEG-PLGA (PolyVivo AK037) from PolySciTech (www.polyscitech.com) to generate nanorods and analyzed these using a combination of atomic force microscopy and infrared spectroscopy. These nano-analysis techniques allowed the researchers to measure the various mechanical, structural, and chemical properties of even a single nanoparticle with incredible precision and accuracy. This research holds promise to allow for improved characterization of nanoparticles which will enable better designs and synthesis in the future. Read more: Khanal, Dipesh, Bokai Zhang, Iqbal Ramzan, Curtis Marcott, Quan Li, and Wojciech Chrzanowski. "Probing Chemical and Mechanical Nanodomains in Copolymer Nanorods with Correlative Atomic Force Microscopy—Nanocorrescopy." Particle & Particle Systems Characterization (2018). https://onlinelibrary.wiley.com/doi/abs/10.1002/ppsc.201700409

“Abstract: The interplay between size, shape, mechanical properties, and surface chemistry of nanoparticles orchestrates cellular internalization, toxicity, circulation time, and biodistribution. Therefore, the safety of nanoparticles hinges on our ability to quantify nanoscale physicochemical characteristics. Current characterization tools, due to their limited resolution, are unable to map these properties correlatively at nanoscale. An innovative use of atomic force microscopybased techniques, namely nanocorrescopy, overcomes this limitation and offers multiprobe capability to map mechanical (viscous and elastic) and chemical domains of nanoparticles correlatively. The strengths of this approach are demonstrated using polymer composite nanorods: mPEGPLGA ((mPEG–methoxypoly (ethylene glycol)bpoly (lacticcoglycolic) acid). Precise distribution of PLGA (monomers of lactide and glycolide) and poly(ethylene glycol) (PEG) polymer across nanorods is identified. The hydrophobic lactide component is found predominantly at the apex, while hydrophilic glycolide and PEG assembled at the body of the nanorods and correlate with a gradient of nanomechanical properties. New knowledge of how both nanochemical domains and nanomechanical properties are distributed across the nanorod will allow elucidating the interactions of nanorods with the proteins and biomolecules in the future, which will directly influence the fate of nanorods in vivo and will guide new synthesis methods.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

PEG-PLA from PolySciTech used in development of ocular-delivery system to treat inflammation

Friday, April 13, 2018, 4:56 PM ET

Inflammatory diseases are typified by an over-reaction of the human immune system against either some trigger or, in some-cases, without a specific trigger. Many diseases are caused by inflammation, however delivery of anti-inflammatory drugs is not always easily accomplished due to location or other disease complications. Recently, researchers at Stony Brook University and Medicon Pharmaceuticals utilized PEG-PLA (Polyvivo AK005) from PolyScitech (www.polyscitech.com) to generate anti-inflammatory nanoparticles for delivery of Phospho-sulindac to the ocular region. Read more: Robert A. Honkanen, Liqun Huang, Gang Xie, Basil Rigas “Phospho-sulindac is efficacious in an improved concanavalin a-based rabbit model of chronic dry eye disease” Translational Research (2018) https://www.sciencedirect.com/science/article/pii/S1931524418300562

“Abstract: Dry eye disease (DED), an inflammatory disease of the ocular surface, affects 15% of humans worldwide. No satisfactory treatment exists for DED partly due to the lack of informative animal models of this disease. We evaluated the anti-inflammatory phosphosulindac (PS) for the treatment of DED, using a new rabbit model of chronic DED. In this model, based on the Concanavalin A (Con A) acute DED model, we injected weekly x3 all lacrimal glands with ConA under ultrasound guidance, which prolonged DED to >3 weeks; and used concurrently four parameters of efficacy: tear break up time (TBUT), tear osmolarity, Schirmer's test, and tear lactoferrin levels, making efficacy assessment robust. Rabbits with DED (n=8-10 eyes/group) were treated topically with PS or vehicle 3x/day for 21 days. PS restored to normal TBUT, tear osmolarity and lactoferrin levels (p<0 .0001="" 1="" 6="" 8="" a="" abbreviations:="" account="" acid="" activated="" activation="" activity="" albumin="" amp="" an="" and="" animal="" anti-inflammatory="" apparent="" assay="" b="" beta="" bovine="" break="" bsa="" buffered="" but="" c-jun="" cause="" cells="" completely="" con="" concanavalin="" concentration="" cornea.="" cornea="" corneal="" cyclosporine="" ded.="" ded="" deviation="" diclofenac="" did="" disease="" dodecyl="" drug="" drugs="" dry="" e2="" effect="" effects="" efficacious="" efficacy="" electophoretic="" elisa="" emsa="" enzyme-linked="" eosin="" erk="" error="" establish="" evaluation="" extracellular="" eye="" factor="" for="" further="" gland="" glycol-block-polylactic="" growth="" h="" had="" half="" hematoxylin="" ic50="" il-1="" il-6="" il-8="" ilg="" immunoprecipitation="" immunosorbent="" improve="" in="" indicate="" inferior="" inhibitory="" interleukin="" international="" its="" iu="" jnk="" kappa-light-chain-enhancer="" ketorolac="" kinases="" lacrimal="" levels="" lifitegrast.="" likely="" list="" mapks="" matrix="" maximal="" mean="" melt="" merits="" metalloproteinase="" milliliter="" minute="" mitogen="" ml="" mmp-1="" mmp-9="" mmp="" mmps.="" mmps="" mobility="" model="" more="" much="" n-terminal="" nearly="" new="" nf-="" no="" nonsteroidal="" not="" nsaids="" nuclear="" nzw="" o:p="" ocular="" of="" on="" ophthalmic="" or="" orbital="" oslg="" osmolarity="" our="" palpebral="" pbs="" peg-pla="" per="" pge2="" phosphate="" phosphosulindac="" polyethylene="" portion="" preserved="" progstaglandin="" protein="" ps-treated="" ps="" pslg="" rabbits.="" radio="" regulated="" results="" revolutions="" ripa="" rpm="" s="" safety.="" saline="" schirmer="" sd="" sds="" sem="" serum="" shift="" showed="" side="" signal="" significantly="" slg="" sodium="" standard="" stt="" studies="" suitable="" sulphate="" superior="" suppressed="" tbut="" tear="" tears="" test.="" test="" tgf-="" than="" that="" the="" time="" tosm="" transforming="" two="" ultrasonography="" units="" up="" us="" was="" were="" white="" zealand="">

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

PEG-PLGA from PolySciTech used in development of dual-drug loaded nanoparticles for cisplatin-resistant ovarian cancer treatment

Monday, April 9, 2018, 4:16 PM ET

Despite effective first-line therapies based on platinum-type drugs, ovarian cancer remains one of the deadliest gynecological diseases in the USA. The incidence of relapse is high, as is the development of platinum-resistant ovarian cancer lines that cannot be treated well using cisplatin. Recently, researchers at University of North Carolina at Chapel Hill, Westminster College, Peking Union Medical College and China Medical University (China) used mPEG-PLGA (PolyvivoAK029) and PLGA ( PolyVivo AP087) from PolySciTech (www.polyscitech.com) to develop nanoparticles that deliver both wortmannin and cisplatin. They found this co-delivery system was very effective against ovarian cancer models in which the cancer was resistant to platinum-based drugs, as the wortmannin prevented the cancer from repairing its own DNA. This research holds promise for development of therapies against drug-resistant cancers. Read more: Zhang, Maofan, C. Tilden Hagan, Yuangzeng Min, Hayley Foley, Xi Tian, Feifei Yang, Yu Mi et al. "Nanoparticle co-delivery of wortmannin and cisplatin synergistically enhances chemoradiotherapy and reverses platinum resistance in ovarian cancer models." Biomaterials (2018). https://www.sciencedirect.com/science/article/pii/S0142961218302333

“Abstract: Most ovarian cancer patients respond well to initial platinum-based chemotherapy. However, within a year, many patients experience disease recurrence with a platinum resistant phenotype that responds poorly to second line chemotherapies. As a result, new strategies to address platinum resistant ovarian cancer (PROC) are needed. Herein, we report that NP co-delivery of cisplatin (CP) and wortmannin (Wtmn), a DNA repair inhibitor, synergistically enhances chemoradiotherapy (CRT) and reverses CP resistance in PROC. We encapsulated this regimen in FDA approved poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) NPs to reduce systemic side effects, enhance cellular CP uptake, improve Wtmn stability, and increase therapeutic efficacy. Treatment of platinum-sensitive ovarian cancer (PSOC) and PROC murine models with these dual-drug loaded NPs (DNPs) significantly reduced tumor burden versus treatment with combinations of free drugs or single-drug loaded NPs (SNPs). These results support further investigation of this NP-based, synergistic drug regimen as a means to combat PROC in the clinic. Keywords: Nanoparticle; Combination therapy; Platinum resistance; Treatment synergy; Ovarian cancer”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

Mal-PEG-PLGA from PolySciTech used in development of oral-exanatide formulation for improved diabetes treatment.

Monday, April 9, 2018, 4:15 PM ET

The incidence of type 2 diabetes has expanded rapidly over the past several decades and is characterized by uncontrolled blood-sugar. Exanatide is a peptide based drug which acts to increase the pancreas response for insulin secretion as a means to control blood sugar. Due to the sensitivity of this peptide to degradation, as well as its poor bioavailability, it is currently only available as an injection. Recently, researchers at Yantai University and Binzhou Medical University (China) used Mal-PEG-PLGA (PolyVivo AI020) and PEG-PLGA (AK037) from PolySciTech (www.polyscitech.com) to develop a transferrin-coated exenatide delivery nanoparticle system that could be ingested and had high bioavailablity. This research holds promise for the development of improved oral diabetes treatment options. Read more: Zhang, Liping, Yanan Shi, Yina Song, Dongyu Duan, Xuemei Zhang, Kaoxiang Sun, and Youxin Li. "Tf ligand-receptor-mediated exenatide-Zn2+ complex oral-delivery system for penetration enhancement of exenatide." Journal of Drug Targeting just-accepted (2018): 1-36. https://www.tandfonline.com/doi/abs/10.1080/1061186X.2018.1455839

“Abstract: Safe and effective oral delivery of peptide is a challenge. Here, we used exenatide and zinc ions (Zn2+) to form a complex to explore a meaningful oral-targeted drug-delivery system. Polyethylene glycol-poly(lactic acid-co-glycolic acid) (PEG-PLGA) was used to prepare nanoparticles (NPs) to escape the degradation caused by gastrointestinal enzymes. Transferrin (Tf) was used as a targeting group. PEG-PLGA-NPs and Tf-modified exenatide-Zn2+-loaded NPs (Tf-PEG-PLGA-NPs) were uniformly sized spheres according to transmission electron microscopy. The results of pharmacodynamic and pharmacokinetic investigations in vivo were consistent with in vitro studies using Caco-2 cells. Tf enhanced NPs transport in cell-uptake and transmembrane-transport experiments. Our results showed that the relative bioavailability of Tf-exenatide-Zn2+-NPs was higher than that of exenatide-Zn2+-NPs. The relative bioavailability of Tf-exenatide-Zn2+-NPs versus subcutaneous injection of exenatide was 6.45%. This was a preliminary exploration of the oral administration of exenatide, that data from which can be used for future investigations. Keywords: transferrin, exenatide-Zn2+, PEG-PLGA, targeted nanoparticles, oral delivery”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

PLGA from PolySciTech used in development of ellipsoid-shaped/lipid-coated particles with controlled cell interaction

Monday, April 9, 2018, 4:14 PM ET

By typical manufacturing techniques, microparticles are simple, spherical, homogenous structures with little feature of interest. This is, effectively, the only configuration possible by conventional emulsion-type manufacturing techniques. There are a great deal of potential applications for developing microparticles which do not obey this simple shape. Recently, researchers at Johns Hopkins University used PLGA (PolyVivo AP087) from PolySciTech (www.polyscitech.com) to develop oblong-shaped microparticles with a carefully controlled coating of a lipid shell bearing various moieties. They investigated the interactions of these particles with cells and proteins and found that ellipsoid particles were resistant to macrophage uptake as well as had several other interesting features. This research holds promise for the development of advanced drug-delivery platforms as well as for other biomedical applications. Read more: Meyer, Randall A., Mohit P. Mathew, Elana Ben-Akiva, Joel C. Sunshine, Ron B. Shmueli, Qiuyin Ren, Kevin J. Yarema, and Jordan J. Green. "Anisotropic Biodegradable Lipid Coated Particles for Spatially Dynamic Protein Presentation." Acta Biomaterialia (2018). https://www.sciencedirect.com/science/article/pii/S1742706118301880

“Abstract: There has been growing interest in the use of particles coated with lipids for applications ranging from drug delivery, gene delivery, and diagnostic imaging to immunoengineering. To date, almost all particles with lipid coatings have been spherical despite emerging evidence that non-spherical shapes can provide important advantages including reduced non-specific elimination and increased target-specific binding. We combine control of core particle geometry with control of particle surface functionality by developing anisotropic, biodegradable ellipsoidal particles with lipid coatings. We demonstrate that these lipid coated ellipsoidal particles maintain advantageous properties of lipid polymer hybrid particles, such as the ability for modular protein conjugation to the particle surface using versatile bioorthogonal ligation reactions. In addition, they exhibit biomimetic membrane fluidity and demonstrate lateral diffusive properties characteristic of natural membrane proteins. These ellipsoidal particles simultaneously provide benefits of non-spherical particles in terms of stability and resistance to non-specific phagocytosis by macrophages as well as enhanced targeted binding. These biomaterials provide a novel and flexible platform for numerous biomedical applications. Statement of Significance: The research reported here documents the ability of non-spherical polymeric particles to be coated with lipids to form anisotropic biomimetic particles. In addition, we demonstrate that these lipid-coated biodegradable polymeric particles can be conjugated to a wide variety of biological molecules in a “click-like” fashion. This is of interest due to the multiple types of cellular mimicry enabled by this biomaterial based technology. These features include mimicry of the highly anisotropic shape exhibited by cells, surface presentation of membrane bound protein mimetics, and lateral diffusivity of membrane bound substrates comparable to that of a plasma membrane. This platform is demonstrated to facilitate targeted cell binding while being resistant to non-specific cellular uptake. Such a platform could allow for investigations into how physical parameters of a particle and its surface affect the interface between biomaterials and cells, as well as provide biomimetic technology platforms for drug delivery and cellular engineering. Keywords: Lipids; Polymers; Membrane fluidity; Particle shape; Biomimetic”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

Poly(lactide) from PolySciTech used in generating light-activated shape-changing microparticles

Thursday, April 5, 2018, 4:32 PM ET

Shape memory is an effect in which polymer chains temporarily entangle holding the material in a set shape until the polymer is heated above a specific rubber-glass transition temperature at which point the polymer chains can move and the material naturally forms back into its original shape. Recently, researchers at Johns Hopkins University purchased PLA (PolyVivo AP004) from PolySciTech (www.polyscitech.com) and used it to create a gold nanoparticle loaded microparticle which changes from elongated shapes into spherical shapes when heated gently by exposure to light. This research holds promise to create materials with tunable macrophage uptake for a variety of biomedical applications. Read more: Guo, Qiongyu, Corey J. Bishop, Randall A. Meyer, David R. Wilson, Lauren Olasov, Daphne E. Schlesinger, Patrick T. Mather, James B. Spicer, Jennifer H. Elisseeff, and Jordan J. Green. "Entanglement-Based Thermoplastic Shape Memory Polymeric Particles with Photothermal Actuation for Biomedical Applications." ACS Applied Materials & Interfaces (2018). https://pubs.acs.org/doi/abs/10.1021/acsami.8b01582

“Abstract: Triggering shape memory functionality under clinical hyperthermia temperatures could enable the control and actuation of shape memory systems in clinical practice. For this purpose, we developed light-inducible shape memory microparticles composed of a poly (D,L-lactic acid) (PDLLA) matrix encapsulating gold nanoparticles (Au@PDLLA hybrid microparticles). This shape memory polymeric system for the first time demonstrates the capability of maintaining an anisotropic shape at body temperature with triggered shape memory effect back to a spherical shape at a narrow temperature range above body temperature with a proper shape recovery speed (37 ˚C < T < 45 ˚C). We applied a modified film-stretching processing method with carefully controlled stretching temperature to enable shape memory and anisotropy in these micron-sized particles. Accordingly, we achieved purely entanglement-based shape memory response without chemical crosslinks in the miniaturized shape memory system. Furthermore, these shape memory microparticles exhibited light-induced spatiotemporal control of their shape recovery using a laser to trigger photothermal heating of doped gold nanoparticles. This shape memory system is composed of biocompatible components and exhibits spatiotemporal controllability of its properties, demonstrating potential for various biomedical applications, such as tuning macrophage phagocytosis as demonstrated in this study.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

Malemide-PEG-PLGA and mPEG-PLGA from PolySciTech used in developing ligand-decorated, curcumin-loaded nanoparticles for breast-cancer treatment

Tuesday, April 3, 2018, 4:12 PM ET

There is a greater interface between herbal/traditional medicine and scientific medicine than most know about. Medicine can be derived from many natural sources (e.g. Paclitaxel derived from Pacific Yew tree) and medicinal chemists often focus on discovering new therapeutic agents derived from nature. Tumeric, and more specifically the extracted curcumin, has been of great interest lately due to curcumin’s anti-cancer properties. Simply eating tumeric spice, however, does not yield a significant anticancer effect for the majority of the body as curcumin has very poor absorption across the intestine. However, properly formulated and purified curcumin, can be a very powerful anticancer agent. It has an advantage over other chemotherapeutics in that it has minimal side-effects. Recently, researchers at Yantie University (China) used Maleimide-PEG-PLGA (PolyVivo AI020) and mPEG-PLGA (PolyVivo AK037) from PolySciTech (www.polyscitech.com) to generate curcumin loaded nanoparticles with Fab targeting ligands for treating breast cancer. This research holds promise for effective breast-cancer treatment with minimal chemotherapy side effects. Read more: Duan, Dongyu, Aiping Wang, Ling Ni, Liping Zhang, Xiuju Yan, Ying Jiang, Hongjie Mu, Zimei Wu, Kaoxiang Sun, and Youxin Li. "Trastuzumab-and Fab′ fragment-modified curcumin PEG-PLGA nanoparticles: preparation and evaluation in vitro and in vivo." International Journal of Nanomedicine 13 (2018): 1831. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868600/

“Abstract: Introduction: Nanoparticles (NPs) modified with bio-ligands represent a promising strategy for active targeted drug delivery to tumour. However, many targeted ligands, such as trastuzumab (TMAB), have high molecular weight, limiting their application for targeting. In this study, we prepared Fab’ (antigen-binding fragments cut from TMAB)-modified NPs (Fab′-NPs) with curcumin (Cur) as a model drug for more effective targeting of human epidermal growth factor receptor 2 (HER2/ErbB2/Neu), which is overexpressed on breast cancer cells. Material and methods: The release kinetics was conducted by dialysis bags. The ability to kill HER2-overexpressing BT-474 cells of Fab′-Cur-NPs compared with TMAB-Cur-NPs was conducted by cytotoxicity experiments. Qualitative and quantitative cell uptake studies using coumarin-6 (fluorescent probe)-loaded NPs were performed by fluorescence microscopy and flow cytometry. Pharmacokinetics and biodistribution experiments in vivo were assessed by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Results: The release kinetics showed that both Fab′-Cur-NPs and TMAB-Cur-NPs provided continuous, slow release of curcumin for 72 h, with no significant difference. In vitro cytotoxicity experiments showed that Fab′-Cur-NPs manifested prominent ability to kill HER2-overexpressing BT-474 cells compared with TMAB-Cur-NPs. Qualitative and quantitative cell uptake studies indicated that the accumulation of Fab′-NPs was greater than that of TMAB-NPs in BT-474 (HER2+) cells; However, there was no significant difference in MDA-MB-231 (HER2−) cells. Pharmacokinetics and biodistribution experiments in vivo demonstrated that the half-life (t1/2) and area under the blood concentration-time curve (AUC0-t) of Fab′-Cur-NPs increased 5.30-fold and 1.76-fold relative to those of TMAB-Cur-NPs, respectively. Furthermore, the tumor accumulation of Fab′-Cur-NPs was higher than that of TMAB-Cur-NPs. Conclusion: Fab′ fragment has greater capacity than the intact antibody to achieve tumor targeting through NP-based delivery. Keywords: trastuzumab-modified curcumin nanoparticles, Fab′-modified curcumin nanoparticles, pharmacokinetics, biodistribution, tumour targeting, breast cancer”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

PLGA from PolySciTech used in development of tannin-inspired antimicrobial bio-adhesives

Thursday, March 22, 2018, 9:37 PM ET

A valuable tool for wound-healing and surgical procedures is tissue adhesives which can bind tissues together and allow them to regrow. Due to the potential for infection, it is desirable for these adhesives to have antibiotic properties. Recently, researchers at Pennsylvania State University, Zhejiang Wanli University, Harbin Engineering University, and Jiangxi Provincial Children’s Hospital used PLGA (PolyVivo AP154) from PolySciTech (www.polyscitech.com) to act as a biocompatibility control for testing the cytotoxicity of their developed systems. This research holds promise to improve would healing and prevent infections. Read more: Guo, Jinshan, Wei Sun, Jimin Peter Kim, Xili Lu, Qiyao Li, Min Lin, Oliver Mrowczynski et al. "Development of tannin-inspired antimicrobial bioadhesives." Acta Biomaterialia (2018). https://www.sciencedirect.com/science/article/pii/S1742706118301284

“Abstract: Tissue adhesives play an important role in surgery to close wounds, seal tissues, and stop bleeding, but existing adhesives are costly, cytotoxic, or bond weakly to tissue. Inspired by the water-resistant adhesion of plant-derived tannins, we herein report a new family of bioadhesives derived from a facile, one-step Michael addition of tannic acid and gelatin under oxidizing conditions and crosslinked by silver nitrate. The oxidized polyphenol groups of tannic acid enable wet tissue adhesion through catecholamine-like chemistry, while both tannic acid and silver nanoparticles reduced from silver nitrate provide antimicrobial sources inherent within the polymeric network. These tannin-inspired gelatin bioadhesives are low-cost and readily scalable and eliminate the concerns of potential neurological effect brought by mussel-inspired strategy due to the inclusion of dopamine; variations in gelatin source (fish, bovine, or porcine) and monomer feeding ratios resulted in tunable gelation times (36 s to 8 min), controllable degradation (up to 100% degradation within a month), considerable wet tissue adhesion strengths (up to 3.7 times to that of fibrin glue), excellent cytocompatibility, as well as antibacterial and antifungal properties. The innate properties of tannic acid as a natural phenolic crosslinker, molecular glue, and antimicrobial agent warrant a unique and significant approach to bioadhesive design. Keywords: tannin; polyphenol; gelatin; bioadhesives; antimicrobial; medical device”


BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

Maleimide-PEG-PLGA from PolySciTech used in development of targeted nanoparticle brain-cancer therapy

Thursday, March 22, 2018, 9:35 PM ET

Brain cancer is doubly difficult to treat as most chemotherapeutics are cytotoxic and uptake to the tumor is poor due to the blood-brain-barrier. Recently, researchers at Yantai University (China) used PLGA-PEG-Mal (Polyvivo AI020) from PolySciTech (www.polyscitech.com) to generate targeted nanoparticles for treating glioma. This research holds promise for improved therapy of brain cancer. Read more: Hua, Hongchen, Xuemei Zhang, Hongjie Mu, Qingqing Meng, Ying Jiang, Yiyun Wang, Xiaoyan Lu et al. "RVG29-modified Docetaxel-loaded nanoparticles for brain-targeted glioma therapy." International Journal of Pharmaceutics (2018). https://www.sciencedirect.com/science/article/pii/S0378517318301753

“Abstract: Gliomas are the most common malignant brain tumor, but treatment is limited by the blood–brain barrier (BBB), especially for chemotherapeutic drugs. Although some chemotherapy drugs can pass through the BBB, many of these agents are toxic to normal brain tissue. To maximize therapeutic effects, chemotherapeutic drugs must accumulate at the glioma site. In this study, a specific ligand (the RVG29 peptide) that can combine with acetylcholine receptors was conjugated to polyethylene glycol-modified poly-(D,L-lactide-co-glycolide) (PEG-PLGA) to develop a targeted carrier; preparation of the targeted docetaxel nanoparticles (DTX-NPs) was performed by the nanoprecipitation method. The NPs were approximately 110 nm and had smooth surfaces. Enzyme-linked immunoassay results showed that the amount of receptor on the surface of glioma cells was 2.04-fold higher than that of nonmalignant cells, which may promote accumulation of RVG29-modified NPs at the targeting site. NPs showed targeting properties for glioma cells compared with the non-targeting NPs in an in vitro cellular uptake test. Targeted NPs also showed better BBB penetration in an in vitro model. In vivo tests indicated that RVG29-PEG-PLGA-NPs could selectively accumulate in intracranial glioma tissue. In conclusion, these results indicated that the RVG29-modified NPs have potential efficacy for glioma therapy. Keywords: Brain-targeting; glioma; RVG29; blood–brain barrier; Docetaxel”
BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

Fluorescent-PLGA and PLGA-PEG-Mal from PolySciTech used in study on Fab-targeting of nanoparticles

Monday, March 19, 2018, 6:27 PM ET

Targeted nanoparticles have come to the forefront recently for their application towards cancer by allowing the particles to bind to specific sites on tumors. There are many factors, however, which can interfere with this process and not all of them are well understood yet. Recently, researchers at Universidade do Porto (Portugal) and Uppsala University (Sweden) utilized fluorescently-tagged PLGA (PLGA-FKR648, AV015) and PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) to create Fab-decorated nanoparticles bearing a fluorescent tracer. These particles were used, along with a series of surfactants, to determine the impact these surfactants had on the targeting capabilities of these nanoparticles. This research holds promise to help in generation of more effective targeted nanoparticle systems by optimizing the surfactant utilized. Read more: Kennedy, Patrick J., Ines Perreira, Daniel Ferreira, Marika Nestor, Carla Oliveira, Pedro L. Granja, and Bruno Sarmento. "Impact of Surfactants on the Target Recognition of Fab-Conjugated PLGA Nanoparticles." European Journal of Pharmaceutics and Biopharmaceutics (2018). https://www.sciencedirect.com/science/article/pii/S0939641118301784

“Abstract: Targeted drug delivery with nanoparticles (NPs) requires proper surface ligand presentation and availability. Surfactants are often used as stabilizers in the production of targeted NPs. Here, we evaluated the impact of surfactants on ligand functionalization and downstream molecular recognition. Our model system consisted of fluorescent poly(lactic-co-glycolic acid) (PLGA) NPs that were nanoprecipitated in one of a small panel of commonly-used surfactants followed by equivalent washes and conjugation of an engineered Fab antibody fragment. Size, polydispersity index and zeta potential were determined by dynamic light scattering and laser Doppler anemometry, and Fab presence on the NPs was assessed by enzyme-linked immunosorbent assay. Most importantly, Fab-decorated NP binding to the cell surface receptor was monitored by fluorescence-activated cell sorting. 2% polyvinyl alcohol, 1% sodium cholate, 0.5% Pluronic F127 (F127) and 2% Tween-80 were initially tested. Of the four surfactants tested, PLGA NPs in 0.5% F127 and 2% Tween-80 had the highest cell binding. These two surfactants were then retested in two different concentrations, 0.5% and 2%. The Fab-decorated PLGA NPs in 2% F127 had the highest cell binding. This study highlights the impact of common surfactants and their concentrations on the downstream targeting of ligand-decorated NPs. Similar principles should be applied in the development of future targeted nanosystems where surfactants are employed. Keywords: Targeted nanoparticles; PLGA nanoparticles; surfactant; Fab antibody fragment”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment.


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