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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PLGA from PolySciTech used in development of iron-chelator nanodelivery system as a treatment for cancer

Wednesday, September 4, 2019, 4:32 PM ET

An ideal chemotherapeutic would be a compound which is highly toxic towards cancerous cells but relatively benign towards normal (healthy) cells. Most conventional chemotherapeutics (such as paclitaxel, 5FU, docetaxel, etc.) are not so selective and rather present a generic propensity to prevent growth of both cancerous and healthy cells leading to severe side-effects. Research has identified compounds which present limited toxicity against normal cells while maintaining high efficacy against cancer cells. Recently, researchers at University of Houston and The Pennsylvania State University used PLGA (AP023 and AP165) from PolySciTech (www.polyscitech.com) to create nanoparticles for delivery of a novel anticancer chelator compound Dp44mT. This research holds promise to provide a novel means of treating cancer with limited side effects. Read more: Claire K. Holley, You Jung Kang, Chung-Fan Kuo, Mohammad Reza Abidian, Sheereen Majd “Development and In Vitro Assessment of an Anti-Tumor Nano-Formulation” Colloids and Surfaces B: Biointerfaces 2019, 110481 https://www.sciencedirect.com/science/article/pii/S0927776519306253.

“Highlights: Iron chelator Dp44mT was efficiently encapsulated in PLGA NPs of 50-120 nm size. Dp44mT-NPs were highly toxic to glioma cell lines, U251 and U87, with IC50

PLGA-PEG-COOH from PolySciTech used in research on acoustic-microfluidic techniques to generate nanoparticles

Wednesday, September 4, 2019, 3:39 PM ET

There are many different techniques which can be applied to the generation of nanoparticles and the method applied drastically affects the particles properties. Notably, microfluidic techniques enable the generation of extremely reproducible nanoparticles with tight sizing control. Recently, researchers at Duke University used PLGA-PEG-COOH (AI056, AI076, AI078, and AI171) from PolySciTech (www.polyscitech.com) to generate nanoparticles by a novel acoustic-microfluidic mechanism. This research holds promise for the generation of highly controlled nanoparticles for drug-delivery applications. Read more: Huang, Po‐Hsun, Shuaiguo Zhao, Hunter Bachman, Nitesh Nama, Zhishang Li, Chuyi Chen, Shujie Yang, Mengxi Wu, Steven Peiran Zhang, and Tony Jun Huang. "Acoustofluidic Synthesis of Particulate Nanomaterials." Advanced Science (2019): 1900913. (https://onlinelibrary.wiley.com/doi/full/10.1002/advs.201900913)

“Abstract: Synthesis of nanoparticles and particulate nanomaterials with tailored properties is a central step toward many applications ranging from energy conversion and imaging/display to biosensing and nanomedicine. While existing microfluidics‐based synthesis methods offer precise control over the synthesis process, most of them rely on passive, partial mixing of reagents, which limits their applicability and potentially, adversely alter the properties of synthesized products. Here, an acoustofluidic (i.e., the fusion of acoustic and microfluidics) synthesis platform is reported to synthesize nanoparticles and nanomaterials in a controllable, reproducible manner through acoustic‐streaming‐based active mixing of reagents. The acoustofluidic strategy allows for the dynamic control of the reaction conditions simply by adjusting the strength of the acoustic streaming. With this platform, the synthesis of versatile nanoparticles/nanomaterials is demonstrated including the synthesis of polymeric nanoparticles, chitosan nanoparticles, organic–inorganic hybrid nanomaterials, metal–organic framework biocomposites, and lipid‐DNA complexes. The acoustofluidic synthesis platform, when incorporated with varying flow rates, compositions, or concentrations of reagents, will lend itself unprecedented flexibility in establishing various reaction conditions and thus enable the synthesis of versatile nanoparticles and nanomaterials with prescribed properties.”

PLA from PolySciTech used in analysis of mechanical and physical properties for engineering applications

Friday, August 30, 2019, 3:30 PM ET

If you have ever carried groceries in a plastic bag, you are familiar with mechanical deformation of polymers. Notably, for LDPE (material used to make bags), pulling on the polymer causes a series of transitions to occur in which the polymer chains pull out in the direction of the force causing the polymer to grow hard and crystalline in the direction of deformation. This is why when you grab the bag handles they first draw out and grow brighter, narrower, and harder as the polymer elongates under the weight of the stuff inside. At some point the chains have been pulled out as far as they will go and the bag handles become very crystalline and strong enough to be very painful for your hands. All of this is due to polymer transitions under mechanical stress. Recently, researchers at University of Wisconsin used PLA (AP164) from PolySciTech (www.polyscitech.com) to create PLA films for testing of physical and mechanical properties of these polymers. This research holds promise to provide for improved use of these polymers as engineering materials. Read more: Bennin, Trevor, Josh Ricci, and M. D. Ediger. "Enhanced Segmental Dynamics of Poly (lactic acid) Glasses during Constant Strain Rate Deformation." Macromolecules (2019). https://pubs.acs.org/doi/abs/10.1021/acs.macromol.9b01363

“The combined effects of temperature and deformation on the segmental dynamics of poly(lactic acid) (PLA) glasses were investigated by using probe reorientation measurements. Constant strain rate deformations, with strain rates between 6 × 10–6 and 3 × 10–5 s–1, were performed on PLA glasses at temperatures between Tg – 15 K and Tg – 25 K. Deformation decreases the segmental relaxation time by up to a factor of 30 relative to the undeformed state. The segmental relaxation time in the postyield regime is related to the local strain rate via a power law, with exponents similar to those reported for lightly cross-linked PMMA. The Kohlrausch–Williams–Watts exponent, βKWW, commonly interpreted in terms of the width of the distribution of segmental relaxation times, changes from the undeformed state to the postyield regime, indicating a significant narrowing of the relaxation spectrum. We observe that βKWW is correlated to the deformation-induced increase of segmental mobility for PLA, as was reported for PMMA. The similar responses of PLA and PMMA to deformation suggest that the observed effects are the generic consequences of constant strain rate deformation on the segmental dynamics of polymer glasses.”

PLGA, PEG-PLGA, PLGA-Folate from PolySciTech used in research on chemotherapeutic nanocarriers

Monday, August 19, 2019, 4:39 PM ET

There are a multitude of nanoparticle strategies currently in development for applications towards treatment of cancer. Despite this, there is still a great deal which remains to be discovered in terms of the exact nature of the nanoparticle/biological interactions. Additionally, the optimal formulation approach remains to be determined. Recently, researchers at Wroclaw University (Poland) used PLGA (AP022), mPEG-PLGA (AK037), and PLGA-Folate (AO037) from PolySciTech (www.polyscitech.com) to develop different types of nanoparticles and tested their use for chemotherapy delivery. This research holds promise for improved therapies against cancer in the future. Read more: Bazylińska, Urszula, Julita Kulbacka, and Grzegorz Chodaczek. "Nanoemulsion Structural Design in Co-Encapsulation of Hybrid Multifunctional Agents: Influence of the Smart PLGA Polymers on the Nanosystem-Enhanced Delivery and Electro-Photodynamic Treatment." Pharmaceutics 11, no. 8 (2019): 405. https://www.mdpi.com/1999-4923/11/8/405

“Abstract: In the present study, we examined properties of poly(lactide-co-glycolide) (PLGA)-based nanocarriers (NCs) with various functional or “smart” properties, i.e., coated with PLGA, polyethylene glycolated PLGA (PEG-PLGA), or folic acid-functionalized PLGA (FA-PLGA). NCs were obtained by double emulsion (water-in-oil-in-water) evaporation process, which is one of the most suitable approaches in nanoemulsion structural design. Nanoemulsion surface engineering allowed us to co-encapsulate a hydrophobic porphyrin photosensitizing dye—verteporfin (VP) in combination with low-dose cisplatin (CisPt)—a hydrophilic cytostatic drug. The composition was tested as a multifunctional and synergistic hybrid agent for bioimaging and anticancer treatment assisted by electroporation on human ovarian cancer SKOV-3 and control hamster ovarian fibroblastoid CHO-K1 cell lines. The diameter of PLGA NCs with different coatings was on average 200 nm, as shown by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. We analyzed the effect of the nanocarrier charge and the polymeric shield variation on the colloidal stability using microelectrophoretic and turbidimetric methods. The cellular internalization and anticancer activity following the electro-photodynamic treatment (EP-PDT) were assessed with confocal microscopy and flow cytometry. Our data show that functionalized PLGA NCs are biocompatible and enable efficient delivery of the hybrid cargo to cancer cells, followed by enhanced killing of cells when supported by EP-PDT. Keywords: smart nanocarriers; folic acid; verteporfin; cisplatin; SKOV-3 cells; CHO-K1 cells; electroporation; theranostic cargo; double emulsion approach”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register at http://bpcrconference.com

Maleimide-PEG-PLGA from PolySciTech used in development of bladder cancer therapy

Monday, August 19, 2019, 4:38 PM ET

One treatment option for bladder cancer is delivery of chemotherapeutics directly into the bladder itself (Intravesical Therapy). Delivery of chemotherapeutics to bladder cancer tumors by this method is difficult due to the low permeability of the bladder, periodic voiding, and other limitations. Recently, researchers at University of Reading (United Kingdom), Al-Farabi Kazakh National University (Kazakhstan), Heinz Maier-Leibnitz Zentrum(Germany) and Harvard University used PLGA-PEG-Mal (AI020, AI109) from PolySciTech (www.polyscitech.com) to develop muco-adhesive nanoparticles. This research holds promise to provide for improved therapeutic strategies against bladder cancer. Read more: Kaldybekov, Daulet B., Sergey K. Filippov, Aurel Radulescu, and Vitaliy V. Khutoryanskiy. "Maleimide-functionalised PLGA-PEG nanoparticles as mucoadhesive carriers for intravesical drug delivery." European Journal of Pharmaceutics and Biopharmaceutics (2019). https://www.sciencedirect.com/science/article/abs/pii/S0939641119307258

“Abstract: Low permeability of the urinary bladder epithelium, poor retention of the chemotherapeutic agents due to dilution and periodic urine voiding as well as intermittent catheterisations are the major limitations of intravesical drug delivery used in the treatment of bladder cancer. In this work, maleimide-functionalised poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG-Mal) nanoparticles were developed. Their physicochemical characteristics, including morphology, architecture and molecular parameters have been investigated by means of dynamic light scattering, transmission electron microscopy and small-angle neutron scattering techniques. It was established that the size of nanoparticles was dependent on the solvent used in their preparation and molecular weight of PEG, for example, 105 ± 1 nm and 68 ± 1 nm particles were formed from PLGA20K-PEG5K in dimethyl sulfoxide and acetone, respectively. PLGA-PEG-Mal nanoparticles were explored as mucoadhesive formulations for drug delivery to the urinary bladder. The retention of fluorescein-loaded nanoparticles on freshly excised lamb bladder mucosa in vitro was evaluated and assessed using a flow-through fluorescence technique and Wash Out50 (WO50) quantitative method. PLGA-PEG-Mal nanoparticles (NPs) exhibited greater retention on urinary bladder mucosa (WO50 = 15 mL) compared to maleimide-free NPs (WO50 = 5 mL). The assessment of the biocompatibility of PEG-Mal using the slug mucosal irritation test revealed that these materials are non-irritant to mucosal surfaces. Graphical abstract: Schematic illustration depicting the mechanism of enhanced mucoadhesion of PLGA-PEG-Mal nanoparticles on urinary bladder mucosa. Keywords: urinary bladder intravesical drug delivery PLGA-PEG maleimide nanoparticles small-angle neutron scattering slug mucosal irritation test muco-adhesion Wash Out50 (WO50)”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register at http://bpcrconference.com

BPCR Registration Deadlines Approaching

Monday, August 19, 2019, 2:35 PM ET

Registration deadlines for BPCR, a free, 1-day scientific-networking conference hosted by Akina, Inc. on Aug 28, 2019, are approaching. See more and register at bpcrconference.com
PRESENT/EXHIBIT: Registration to present or exhibit closes August 20th at midnight (EST).
ATTEND: Registration to attend closes August 25th at midnight (EST).
Note that preregistration is not mandatory to attend. It is only required to receive the free lunch.

mPEG-PCL from PolySciTech used in development of thermogel delivery system to treat macular degeneration

Tuesday, August 13, 2019, 4:31 PM ET

Macular degeneration is caused by deterioration of the retina and is an incurable disease that eventually leads to blindness. Although this disease cannot be cured, there are many strategies which can delay its onset and reduce its progression. Recently, researchers at University of South Florida, University of Mississippi, The Maharaja Sayajirao University of Baroda (India), and Airlangga University (Indonesia) used mPEG-PCL (PolyVivo AK036) from PolySciTech (www.polyscitech.com) to develop a thermogel to prevent blindness. Read More: Bhatt, Priyanka, Priya Narvekar, Rohan Lalani, Mahavir Bhupal Chougule, Yashwant Pathak, and Vijaykumar Sutariya. "An in vitro Assessment of Thermo-Reversible Gel Formulation Containing Sunitinib Nanoparticles for Neovascular Age-Related Macular Degeneration." AAPS PharmSciTech 20, no. 7 (2019): 281. https://link.springer.com/article/10.1208/s12249-019-1474-0

“Abstract: Anti-vascular endothelial growth factor agents have been widely used to treat several eye diseases including age-related macular degeneration (AMD). An approach to maximize the local concentration of drug at the target site and minimize systemic exposure is to be sought. Sunitinib malate, a multiple receptor tyrosine kinase inhibitor was encapsulated in poly(lactic-co-glycolic acid) nanoparticles to impart sustained release. The residence time in vitreal fluid was further increased by incorporating nanoparticles in thermo-reversible gel. Nanoparticles were characterized using TEM, DSC, FTIR, and in vitro drug release profile. The cytotoxicity of the formulation was assessed on ARPE-19 cells using the MTT assay. The cellular uptake, wound scratch assay, and VEGF expression levels were determined in in vitro settings. The optimized formulation had a particle size of 164.5 nm and zeta potential of − 18.27 mV. The entrapment efficiency of 72.0% ± 3.5% and percent drug loading of 9.1 ± 0.7% were achieved. The viability of ARPE-19 cells was greater than 90% for gel loaded, as such and blank nanoparticles at 10 μM and 20 μM concentration tested, whereas for drug solution viability was found to be 83% and 71% respectively at above concentration. The cell viability results suggest the compatibility of the developed formulation. Evaluation of cellular uptake, wound scratch assay, and VEGF expression levels for the developed formulations indicated that the formulation had higher uptake, superior anti-angiogenic potential, and prolonged inhibition of VEGF activity compared with drug solution. The results showed successful development of sunitinib-loaded nanoparticle-based thermo-reversible gel which may be used for the treatment of neovascular AMD. KEY WORDS sunitinib PLGA nanoparticles sustained release ocular delivery intravitreal VEGF”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

mPEG-PLGA used in development of bacteria-killing fibers to prevent oral biofilms

Tuesday, August 13, 2019, 4:31 PM ET

Infections of the teeth and gumlines are extremely common and can lead to severe complications especially after surgical implantation as well as in disease states. One strategy to deal with these infections is to generate implant surfaces which release antibacterial agents. Recently, researchers at University of Louisville used mPEG-PLGA (PolyVivo AK026) from PolySciTech (www.polyscitech.com) to develop antibacterial nanoparticles. Read more: Mahmoud, Mohamed Yehia. "Development of BAR-peptide nanoparticles and electrospun fibers for the prevention and treatment of oral biofilms." PhD Dissertation University of Louisville (2019). https://ir.library.louisville.edu/etd/3162/

“Abstract (synopsis): Periodontal diseases are globally prevalent inflammatory disorders that affect ~47% of U.S adults. Porphyromonas gingivalis (Pg) has been identified as a “keystone” pathogen that disrupts host-microbe homeostasis and contributes to the initiation and progression of periodontitis. To address these challenges, we hypothesized that BARsurface modified and BAR-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) may more potently inhibit and disrupt biofilms in vitro and in vivo, relative to free BAR. BAR-encapsulated and BAR-surface modified PLGA NPs were synthesized using adapted double- and single-emulsion techniques, respectively. Electrospun fibers were formed using a uniaxial approach, with different hydrophobic polymers (PLGA, polycaprolactone, poly(L-lactic acid)); each blended with different polyethylene oxide ratios (PEO: 0, 10, 20, or 40% w/w) to achieve maximal release of BAR. Both BAR-encapsulated NPs and EFs were assessed for inhibition of two-species biofilm formation and for disruption of pre-existing biofilms, against an equimolar free BAR concentration. BAR-encapsulated NPs and EFs inhibited biofilm formation (IC50s = 0.7 and 1.3 μM, respectively) in a dose-dependent manner, relative to free BAR (IC50 = 1.3 µM). In addition, BAR-encapsulated NPs and EFs efficiently disrupted established dual-species biofilms (IC50s = 1.3 and 2 μM, respectively). Treatment of Pg/Sg infected mice with BAR-surface modified NPs reduced alveolar bone loss and IL-17 expression almost to the levels of sham-infected mice and to a greater extent than treatment with an equimolar amount of free BAR. The in vitro cytotoxicity studies, which utilized the maximum concentration of BARencapsulated NPs, BAR-surface modified NPs, BAR EFs, and free BAR (1.3 and 3.4 μM) demonstrated > 90% viability for all samples and showed no significant lysis or apoptosis relative to untreated cells. These data suggested that BAR NPs and EFs provide novel and potent platforms to inhibit and disrupt dual-species biofilms.”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

mPEG-PLGA from PolySciTech used in development of brusatol-loaded nanoparticles for cancer therapy

Tuesday, August 13, 2019, 4:30 PM ET

Brusatol, isolated from the Brucea javanica bush, acts to inhibit the Nrf2 signaling pathway within cells which can render chemotherapy resistant tumors susceptible to conventional chemotherapy as well as reduce their overall growth and proliferation. Recently, researchers at Howard University used mPEG-PLGA (PolyVivo AK029) from PolySciTech (www.polyscitech.com) to develop brusatol-loaded nanoparticles for cancer treatment. This research holds promise to provide for improved cancer therapies in the future. Read more: Adesina, S. K., and T. E. Reid. "Nanoparticle Formulation of Brusatol: A Novel Therapeutic Option for Cancers." J Pharm Drug Deliv Res 7 1 (2018): 2. https://pdfs.semanticscholar.org/9b40/be5e366f6759ba168926921be6efae0a0d5c.pdf

“Abstract Objective: Challenges to the use of brusatol for cancer chemotherapy include its reversible and short-lived effect on Nrf2 which is limited to a few hours, its non-selective inhibition of protein synthesis which renders it potentially toxic to non-cancerous cells resulting in adverse effects and poor water solubility. A nanoparticle formulation of brusatol is expected to overcome these challenges and facilitate the clinical use of brusatol. In this proof-of-principle study, a brusatol-loaded nanoparticle formulation is developed and characterized. Method: Brusatol-loaded mPEG-PLGA nanoparticles were prepared using the oil-in-water emulsification solvent diffusion method and characterized. The drug content of the nanoparticle formulation was determined by High Performance Liquid Chromatography. Toxicity of the brusatol-loaded nanoparticles in prostate cancer cell lines was evaluated over 120 hours using the Cell Titer 96® NonRadioactive Cell Proliferation Assay and nanoparticle uptake was studied by confocal microscopy. Results: Scanning electron microscopy revealed the formation of nanoparticles. The average hydrodynamic particle size is 309.23 ± 2.3 nm. The in vitro release isotherm showed a biphasic and sustained release of the encapsulated drug. Data from cytotoxicity studies reveal that the nanoparticle formulation showed more toxicity compared to control brusatol solution in PC-3 and LNCaP cell lines. Confocal microscopy studies showed internalization of the nanoparticles in PC-3 cells at 6 hours. In addition, z-stack images confirm the presence of nanoparticles at various depths within the cells. Conclusion: The stealth nanoparticle formulation allows the sustained release of brusatol with the potential to modulate its short-lived effect on Nrf2. In addition, the potential of the nanoparticle formulation to target the tumor microenvironment via the enhanced permeability and retention effect and prevent toxicity to non-cancerous cells is achieved. We report the preparation and characterization of a stealth nanoparticle formulation of brusatol to facilitate the clinical use of the drug for the treatment of cancers. Keywords: Oxidative stress; Site-specific delivery; Cytotoxicity; Brusatol; Nuclear factor erythroid 2-related factor 2; Protein synthesis inhibitor; Nanoparticle; Sustained release”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

PLGA from PolySciTech used in fundamental research on in-situ forming implant drug release kinetics.

Thursday, August 1, 2019, 10:18 AM ET

One method of delivering drug in a controlled release manner is to load the drug into a biocompatible, water-miscible organic solvent (n-methylpyrrolidinone) along with degradable PLGA. After this solution is injected into a patient the solvent exchanges with the water inside the patient to solidify the PLGA around the drug trapping it until it can be released. This method is used in the popular Atrigel® delivery system which is currently used in clinical products such as sublocade (extended release buprenorphine for addiction therapy). Despite these developments, several factors behind the exact driving mechanisms and controlling factors of in-situ forming gels and their release kinetics still remain to be elucidated. Recently, researchers at Purdue University used PLGA (AP041) from PolySciTech (www.polyscitech.com) to generate a series of in-situ forming implants containing model drug fluorescein. They then carefully tracked the drug release kinetics using a novel MRI methodology to understand the driving factors of release. This research holds promise to improve the development of in-situ implants for drug delivery. Read more: Hopkins, Kelsey A., Nicole Vike, Xin Li, Jacqueline Kennedy, Emma Simmons, Joseph Rispoli, and Luis Solorio. "Noninvasive characterization of In Situ forming implant diffusivity using diffusion-weighted MRI." Journal of Controlled Release (2019). https://www.sciencedirect.com/science/article/pii/S0168365919304067

“Highlights: In situ forming implants (ISFIs) are injectable, long-acting drug release depots. Diffusion-weighted MRI was used as a novel modality to noninvasively analyze ISFIs. DWI can quantify spatial-temporal changes in diffusivity within ISFIs in situ. DWI gives insight into transport properties within ISFIs both in vitro and in vivo. Abstract: In situ forming implants (ISFIs) form a solid drug-eluting depot, releasing drug for an extended period of time after a minimally-invasive injection. Clinical use of ISFIs has been limited because many factors affect drug release kinetics. The aim of this study was to use diffusion-weighted MRI (DWI) to noninvasively quantify spatial-temporal changes in implant diffusivity in situ. ISFIs were formed using poly(lactic-co-glycolic) acid, with a molecular weight of either 15 kDa or 52 kDa, and fluorescein as the mock drug. Drug release, polymer erosion and degradation, and implant diffusivity were analyzed in vitro over 21 days. DWI was also performed in vivo over 5 days. Spatial diffusivity maps of the implant were generated using DWI data. Results showed constant diffusivity at the implant shell ((1.17 ± 0.128) × 10−3 mm2/s) and increasing diffusivity within the interior over time (from (0.268 ± 0.0813) × 10−3 mm2/s during day 1 to (1.88 ± 0.0400) × 10−3 mm2/s at 14 d), which correlated with increasing porosity of the implant microstructure. Implants formed in vivo followed the same diffusivity trend as those in vitro. This study validates the use of DWI to provide novel functional information about implant behavior through its ability to noninvasively characterize transport properties within the implant both in vitro and in vivo. Keywords: in situ forming implants Controlled release Drug delivery MRI Diffusion-weighted imaging Diffusivity.”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

PLLA from PolySciTech used in development of biodegradable tissue scaffold for skin repair

Monday, July 29, 2019, 1:43 PM ET

Tissue healing is a complex process by which damaged or lost tissues are replaced by new tissue. To grow, the cells of the body must have something to adhere too. In normal situations this is called the extracellular matrix which is a layer of proteins and connective components which is present between cells. In cases of severe trauma (i.e. burn wounds) there may not be any connective components to enable the cells to regrow which prevents healing in these cases. In this case, the healing can be improved by use of a tissue scaffold. Recently, researchers at Czech Academy of Sciences, Charles University, Slovak Academy of Sciences, and Technical University of Liberec (Czech Republic) used PLLA (AP047) from PolySciTech (www.polyscitech.com) to generate a skin construct to use in tissue repair. This research holds promise to provide for improved therapy for burn-wound and trauma victims who need scaffolds for skin repair. Read more: Bacakova, Marketa, Julia Pajorova, Antonin Broz, Daniel Hadraba, Frantisek Lopot, Anna Zavadakova, Lucie Vistejnova et al. "A two-layer skin construct consisting of a collagen hydrogel reinforced by a fibrin-coated polylactide nanofibrous membrane." International Journal of Nanomedicine 14 (2019): 5033. http://search.proquest.com/openview/f9c9c6368aada3b8497b393332207137/1?pq-origsite=gscholar&cbl=3933144

“Background: Repairs to deep skin wounds continue to be a difficult issue in clinical practice. A promising approach is to fabricate full-thickness skin substitutes with functions closely similar to those of the natural tissue. For many years, a three-dimensional (3D) collagen hydrogel has been considered to provide a physiological 3D environment for cocultivation of skin fibroblasts and keratinocytes. This collagen hydrogel is frequently used for fabricating tissue-engineered skin analogues with fibroblasts embedded inside the hydrogel and keratinocytes cultivated on its surface. Despite its unique biological properties, the collagen hydrogel has insufficient stiffness, with a tendency to collapse under the traction forces generated by the embedded cells. Methods: The aim of our study was to develop a two-layer skin construct consisting of a collagen hydrogel reinforced by a nanofibrous poly-L-lactide (PLLA) membrane pre-seeded with fibroblasts. The attractiveness of the membrane for dermal fibroblasts was enhanced by coating it with a thin nanofibrous fibrin mesh. Results: The fibrin mesh promoted the adhesion, proliferation and migration of the fibroblasts upwards into the collagen hydrogel. Moreover, the fibroblasts spontaneously migrating into the collagen hydrogel showed a lower tendency to contract and shrink the hydrogel by their traction forces. The surface of the collagen was seeded with human dermal keratinocytes. The keratinocytes were able to form a basal layer of highly mitotically-active cells, and a suprabasal layer. Conclusion: The two-layer skin construct based on collagen hydrogel with spontaneously immigrated fibroblasts and reinforced by a fibrin-coated nanofibrous membrane seems to be promising for the construction of full-thickness skin substitute. Keywords: full-thickness skin substitutes, collagen hydrogel, fibroblast and keratinocyte cocultivation, fibrin, nanostructure”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

2019 CRS Meeting Update: Posters and Presentations available

Monday, July 29, 2019, 1:42 PM ET

Akina’s Scientific Posters and slide-presentation from 2019 Controlled Release Society Annual Meeting are available as full-resolution pdf’s online here (http://polyscitech.com/currentResearch/publications.php): John Garner - Slide Presentation “Complex Sameness: Tests to Determine Properties for PLGA Excipients in Long-Acting Formulations” presented as part of Technology Forum “Implants and Depots – How To meet Challenges in Polymeric Controlled Release with Bioresorbable and Biodurable Materials” at 2019 annual meeting of Controlled Release Society; Posters: “Analysis of the branch units of glucose-poly(lactide-co-glycolide) in Sandostatin® LAR formulation”;“Compositional analysis of glucose-poly(lactide-co-glycolide) in Sandostatin® LAR formulation”;“Separation and analysis of poly(lactide-co-glycolide) in Trelstar® 22.5 mg formulation”;“Effect of solvents and their isomers on dissolution of PLGAs with different lactide:glycolide (L:G) ratios”
Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

Come meet Akina, Inc. at Controlled Release Society (CRS) annual meeting in Valencia, Spain July 20-24th

Wednesday, July 17, 2019, 11:58 AM ET

Representatives from Akina, Inc. (www.akinainc.com) will be attending the CRS meeting in Valencia, Spain July 20-24th (https://2019.controlledreleasesociety.org/valencia). #valencia #crs46 #crs2019


Dr. Kinam Park - “Stars Collide Nanotechnology Big Progress or. Nano Progress” debate (7/22)

John Garner - Presenting "Complex Sameness: Tests to Determine Properties for PLGA Excipients in Long-Acting Formulations" as part of “Implants and Depots – How To meet Challenges in Polymeric Controlled Release with Bioresorbable and Biodurable Materials” (7/21, 8-10AM)

Posters (Poster #’s P501-P504):
Presenter: Justin Hadar

“Analysis of the branch units of glucose-poly(lactide-co-glycolide) in Sandostatin® LAR formulation” J. Hadar, J. Garner, S. Skidmore, H. Park, K. Park, B. Qin, X. Jiang, Y. Wang
“Compositional analysis of glucose-poly(lactide-co-glycolide) in Sandostatin® LAR formulation” J. Hadar, J. Garner, S. Skidmore, H. Park, K. Park, B. Qin, X. Jiang, Y. Wang

Presenter: John Garner
“Separation and analysis of poly(lactide-co-glycolide) in Trelstar® 22.5 mg formulation” J. Garner, J. Hadar, S. Skidmore, H. Park, K. Park, B. Qin, X. Jiang, Y. Wang
“Effect of solvents and their isomers on dissolution of PLGAs with different lactide:glycolide (L:G) ratios” J. Garner, J. Hadar, S. Skidmore, H. Park, K. Park, B. Qin, X. Jiang, Y. Wang

PLGA-PEG-Mal from PolySciTech used in development of nanoparticle-based Parkinson’s disease treatment

Tuesday, July 16, 2019, 2:41 PM ET

Parkinson’s disease is an incurable progressive neurodegenerative disorder in which neural cells within the brain begin to break down and die. Notably, this affects cells which produce dopamine leading to severe chemical imbalances within the brain that create many of the symptoms of Parkinson’s disease. Treating Parkinson’s disease suffers from difficulty in getting the medicinal molecules to cross over the blood-brain-barrier. Recently, researchers at Yantai University, and Shandong Luye Pharmaceutical Co. (China) used Mal-PEG-PLGA (AI109) and mPEG-PLGA (AK104) from PolySciTech (www.polyscitech.com) to generate surface-modified nanoparticles designed to cross the blood-brain barrier. These particles were used as part of a dopamine delivery system. This research holds promise to provide for improved Parkinson’s disease therapies in the future. Read more: Tang, Shengnan, Aiping Wang, Xiuju Yan, Liuxiang Chu, Xiucheng Yang, Yina Song, Kaoxiang Sun et al. "Brain-targeted intranasal delivery of dopamine with borneol and lactoferrin co-modified nanoparticles for treating Parkinson’s disease." Drug delivery 26, no. 1 (2019): 700-707. https://www.tandfonline.com/doi/abs/10.1080/10717544.2019.1636420

“Abstract: Efficient delivery of brain-targeted drugs is highly important for successful therapy in Parkinson’s disease (PD). This study was designed to formulate borneol and lactoferrin co-modified nanoparticles (Lf-BNPs) encapsulated dopamine as a novel drug delivery system to achieve maximum therapeutic efficacy and reduce side effects for PD. Dopamine Lf-BNPs were prepared using the double emulsion solvent evaporation method and evaluated for physicochemical and pharmaceutical properties. In vitro cytotoxicity studies indicated that treatment with dopamine Lf-BNPs has relatively low cytotoxicity in SH-SY5Y and 16HBE cells. Qualitative and quantitative cellular uptake experiments indicated that Lf modification of NPs increased cellular uptake of SH-SY5Y cells and 16HBE cells, and borneol modification can promote the cellular uptake of 16HBE. In vivo pharmacokinetic studies indicated that AUC0–12 h in the rat brain for dopamine Lf-BNPs was significantly higher (p < .05) than that of dopamine nanoparticles. Intranasal administration of dopamine Lf-BNPs effectively alleviated the 6-hydroxydopamine-induced striatum lesion in rats as indicated by the contralateral rotation behavior test and results for striatal monoamine neurotransmitter content detection. Taken together, intranasal administration of dopamine Lf-BNPs may be an effective drug delivery system for Parkinson’s disease. Keywords: Dopamine, lactoferrin, borneol, nose-to-brain targeted nanoparticles, Parkinson’s disease”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

PEG-PLGA and PLGA-Rhodamine from PolySciTech used in research on Nanoparticle adhesion and transportation

Thursday, July 11, 2019, 2:00 PM ET

One of the key questions to answer for targeted therapy to cancer cells is the nature of the surface interaction between the particles and the cancer cells. Optimally, the particles should bind selectively to cancer cells and tumor components and be up-taken into the cancer cells. However, achieving this ideal situation has yet to be achieved. There remains a great deal more to be understood about the nature of the interaction between the particle surface and the cancer cells as well as the impact of various ligands and surfactants on this interaction. Recently, researchers at the University of Maryland utilized PLGA-Rhodamine (AV011), PEG-PLGA (AK010), and PLGA (AP041), from PolySciTech (www.polyscitech.com) to develop a series of nanoparticles and test their surface interactions using a surface-plasmon resonance analytical technique. This research holds promise to improve the efficacy of nanoparticle delivery systems for cancer treatment. Read more: Wadajkar, Aniket S., Jimena G. Dancy, Christine P. Carney, Brian S. Hampton, Heather M. Ames, Jeffrey A. Winkles, Graeme F. Woodworth, and Anthony J. Kim. "Leveraging Surface Plasmon Resonance to Dissect the Interfacial Properties of Nanoparticles: Implications for Tissue Binding and Tumor Penetration." Nanomedicine: Nanotechnology, Biology and Medicine 20 (2019): 102024. https://www.sciencedirect.com/science/article/pii/S154996341930108X

“Abstract: Therapeutic efficacy of nanoparticle-drug formulations for cancer applications is significantly impacted by the extent of intra-tumoral accumulation and tumor tissue penetration. We advanced the application of surface plasmon resonance to examine interfacial properties of various clinical and emerging nanoparticles related to tumor tissue penetration. We observed that amine-terminated or positively-charged dendrimers and liposomes bound strongly to tumor extracellular matrix (ECM) proteins, whereas hydroxyl/carboxyl-terminated dendrimers and PEGylated/neutrally-charged liposomes did not bind. In addition, poly(lactic-co-glycolic acid) (PLGA) nanoparticles formulated with cholic acid or F127 surfactants bound strongly to tumor ECM proteins, whereas nanoparticles formulated with poly(vinyl alcohol) did not bind. Unexpectedly, following blood serum incubation, this binding increased and particle transport in ex vivo tumor tissues reduced markedly. Finally, we characterized the protein corona on PLGA nanoparticles using quantitative proteomics. Through these studies, we identified valuable criteria for particle surface characteristics that are likely to mediate their tissue binding and tumor penetration. Graphical Abstract: We established the application of surface plasmon resonance (SPR) to examine the interfacial properties of multiple clinical and emerging nanoparticle formulations related to tumor tissue penetration. Using this SPR assay, we closely studied the interfacial properties of these nanoparticles, specifically nanoparticle surface chemistries, formulation surfactants, and protein corona components, on binding to tumor ECM proteins. Unexpectedly, we found that all PLGA NP formulations displayed markedly increased binding behavior towards tumor ECM proteins following blood serum incubation, including densely PEG-coated PLGA-PEG NPs. Key words: Surface plasmon resonance (SPR) Protein corona Nanoparticles Non-specific binding Tumor penetration Proteomics”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

PLGA-NH2 from PolySciTech used in development of lung-targeting polymeric microdiscs to treat pulmonary disease

Tuesday, July 9, 2019, 4:25 PM ET

Most drugs administered into the blood stream are rapidly cleared by the body and either metabolized into some other form or removed into the urine or excreted by some other manner. This limits the efficacy of these medicinal compounds. Recently, researchers at Yonsei University and Korea Institute of Radiological and Medical Sciences (Korea) used PLGA-NH2 (AI010) from PolySciTech (www.polyscitech.com) to develop microdiscs designed to accumulate to the lungs. This research holds promise to improve therapies against pulmonary diseases. Read more: Park, Jun Young, Sanghyo Park, Tae Sup Lee, Yong Hwa Hwang, Jung Young Kim, Won Jun Kang, and Jaehong Key. "Biodegradable micro-sized discoidal polymeric particles for lung-targeted delivery system." Biomaterials (2019): 119331. https://www.sciencedirect.com/science/article/pii/S0142961219304302

“Abstract: Various types of particle-based drug delivery systems have been explored for the treatment of pulmonary diseases; however, bio-distribution and elimination of the particles should be monitored for better understanding of their therapeutic efficacy and safety. This study aimed to characterize the biological properties of micro-sized discoidal polymeric particles (DPPs) as lung-targeted drug delivery carriers. DPPs were prepared using a top-down fabrication approach and characterized by assessing size and zeta potential. They were labeled with zirconium-89 (89Zr), and bio-distribution studies and PET imaging were performed for 7 days after intravenous administration. Their hydrodynamic size was 2.8 ± 6.1 μm and average zeta potential was −39.9 ± 5.39 mV. At doses of 5, 12.5, and 25 mg/kg, they showed no acute toxicity in nude mice. Desferrioxamine (DFO)-functionalized 89Zr-labeled DPPs gave a decay-corrected radiochemical yield of 82.1 ± 0.2%. Furthermore, 89Zr-DPPs, from chelate-free labeling methods, showed a yield of 48.5 ± 0.9%. Bio-distribution studies and PET imaging showed 89Zr-DFO-DPPs to be mainly accumulated in the lungs and degraded within 3 d of injection. However, 89Zr-DFO-DPPs showed significantly low uptake in the bone. Overall, our results suggested micro-sized DPPs as promising drug delivery carriers for the targeted treatment of various pulmonary diseases. Keywords: Drug delivery system Discoidal polymeric particle Pulmonary disease Zr-89 PET imaging”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

Polylactide from PolySciTech Used in Research on Biodegradable Adhesives For Environmental Applications

Tuesday, July 9, 2019, 4:15 PM ET

Pollution due to nondegradable plastics and commodity products has created an environmental crisis. Recently, researchers at Purdue University used PLA (AP138) from PolySciTech (www.polyscitech.com) as part of research in developing biodegradable adhesives. This research holds promise to solve environmental problems related to plastics pollution. Read more: Siebert, Heather, and Jonathan J. Wilker. "Deriving Commercial Level Adhesive Performance from a Bio-Based Mussel Mimetic Polymer." ACS Sustainable Chemistry & Engineering (2019). https://pubs.acs.org/doi/abs/10.1021/acssuschemeng.9b02547

“Abstract: Adhesive are critical for holding together the products that we use every day. Most industrial glues are petroleum-based. These materials are strong bonding, but also permanent, leading to difficulties separating, recycling, and reusing the components. Petroleum-based materials only exist in finite quantities and sustainable alternatives are needed for the future. Results presented here are part of our efforts to develop adhesives that are non-toxic, renewably sourced, and allow substrates to be disassembled for recycling. By systematically studying formulation parameters for a bio-based, mussel mimetic polymer, we now have developed a material that is able to compete with commercial bio-based and petroleum-based adhesives in terms of adhesive strengths on multiple substrates.”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

Maleimide-PEG-PLA from PolySciTech used in development of targeted nanoparticle therapy for breast cancer

Friday, July 5, 2019, 10:58 AM ET

Breast cancer is a very common form of cancer representing about 30% of all cancer cases diagnosed. Most common forms of breast cancer are well treated with HER2 targeted therapies and other options however forms of breast cancer which do not have the typical markers on their cell-surface (referenced as ‘Triple-negative’ breast cancer) remain difficult to treat. Recently, researchers at University of Minnesota used PLA-PEG-Mal (AI119) and PLGA-Rhodamine (AV011) from PolySciTech (www.polyscitech.com) to create a perlecan targeted therapy system. Perlecan is a recently discovered marker which holds promise for efficacy against a range of cancers. This research holds promise for improved breast-cancer therapy. Read more: Khanna, Vidhi, Stephen Kalscheuer, Ameya Kirtane, Wenqui Zhang, and Jayanth Panyam. "Perlecan-targeted nanoparticles for drug delivery to triple-negative breast cancer." Future Drug Discovery 1, no. 1 (2019). https://www.future-science.com/doi/abs/10.4155/fdd-2019-0005

“Aim: We previously developed two antibodies that bind to a cell surface protein, perlecan, overexpressed in triple-negative breast cancer (TNBC). The goal of this study was to investigate these antibodies as targeting ligands for nanoparticle-mediated drug delivery. Methods: Paclitaxel-loaded poly(D,L-lactide-coglycolide) nanoparticles were functionalized with antibodies using thiol–maleimide chemistry. Effect of antibody functionalization on therapeutic efficacy of drug-loaded nanoparticles was investigated using in vitro and in vivo models of TNBC. Results: The antibodies were covalently conjugated to nanoparticles without affecting antibody binding affinity or nanoparticle properties. Perlecan-targeted nanoparticles showed improved cell uptake, retention, cytotoxicity in vitro and enhanced tumor growth inhibition in vivo. Conclusion: The data presented here indicates that perlecan-targeted nanoparticles can improve tumor drug delivery to TNBC. Keywords: antibody, perlecan, polymeric nanoparticles, targeted drug delivery, triple-negative breast cancer”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

July 4th Hours

Wednesday, July 3, 2019, 3:07 PM ET

Notice: Akina, Inc. will be closed Thursday, July 4th. Sales services will also be closed July 5th-8th (technical services still available). Orders placed during this time will be processed when we re-open on Tuesday, July 9th, 2019.

PLGA from PolySciTech used in development of platelet membrane-coated nanoparticles for lung-cancer treatment

Tuesday, July 2, 2019, 2:51 PM ET

Delivery of drugs to cancer by nanoparticles is complicated by the presence of clearance mechanisms within the human body which screen the particles and their medicines out before they can have therapeutic effect. One strategy to bypass this is to attach cell-indicating membrane components to the particles so that they present as ‘self’ to the immune system. Recently, researchers at Jilin University (China) used PLGA (AP041) from PolySciTech (www.polyscitech.com) to create docetaxel loaded nanoparticles masked with platelet membranes. This research holds promise for improved therapies against lung-cancer. Read more: Changliang Chi, Fuwei Li, Huibo Liu, Shiyun Feng, Yanjun Zhang, Da Zhou, Rongkui Zhang “Docetaxel-loaded biomimetic nanoparticles for targeted lung cancer therapy in vivo” Journal of Nanoparticle Research July 2019, 21:144 https://doi.org/10.1007/s11051-019-4580-8

“Abstract: Although the nanodrug-loading system provides new ideas for the effective treatment of cancer, the lack of active cancer targeting, easy to be cleared by the reticuloendothelial system (RES), and may cause potential safety issues are still problems that needs urgent solution. Herein, the authors fabricated platelet membrane (PM)-coated docetaxel (DTX)-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (PM/PLGA/DTX) that possessed unique advantages for satisfactory lung cancer therapy. The resulting core–shell nanoplatform exhibited proper size (hydrodynamic diameter was 98.2 nm) for the enhanced permeability and retention (EPR) effect, slowed down the release of loaded DTX, and effectively suppressed the growth of tumor cells in vitro. More importantly, due to the immune escape and cancer-targeting capacities of PM, the PM/PLGA/DTX showed long circulation and effective lung tumor-targeting ability. After administration in vivo antitumor activity, the PM/PLGA/DTX significantly inhibited the tumor growth of A549 cell-bearing nude mice. In addition, the PM/PLGA/DTX strongly reduced the DTX toxicity compared with that of free DTX. Therefore, the results here demonstrated this biomimetic nanoparticle is a promising nanosized drug delivery system for targeted lung cancer therapy. Keywords: Platelet membrane Controlled drug delivery Targeted lung cancer therapy Docetaxel Biomimetic nanoparticles Drug toxicity PLGA Nanomedicine”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

PLGA-PEG-COOH from PolySciTech used in development of nanoparticle therapy for breast cancer.

Monday, July 1, 2019, 4:37 PM ET

Targeting cancer at higher rates than normal tissue is the goal of drug delivery in the cancer sector so as to maximize efficacy with minimal side-effects. Recently, researchers from China Pharmaceutical University Used PLGA-PEG-COOH (AI034) from PolySciTech (www.polyscitech.com) as part of development of aptamer-targeted nanoparticles for cancer delivery. This research holds promise for the development of advanced breast cancer treatment options. Read more: Duan, Tao, Zhuobin Xu, Fumou Sun, Yang Wang, Juan Zhang, Chen Luo, and Min Wang. "HPA aptamer functionalized paclitaxel-loaded PLGA nanoparticles for enhanced anticancer therapy through targeted effects and microenvironment modulation." Biomedicine & Pharmacotherapy 117 (2019): 109121. https://www.sciencedirect.com/science/article/pii/S0753332219310285

“Highlights: Confirming HPA as recognized molecular targets for TNBC therapy. A HPA aptamer-guided anticancer drug delivery system was developed with MDA-MB-231 as a model in vitro and vivo. The system exhibited enhanced anti-invasive and anti-angiogenesis activity through HPA-related signaling pathways. Numerous cancers overexpress HPA and are sensitive to PTX, that make the system as a broad-spectrum anti-cancer agent. Abstract: Breast cancer is a fairly common cancer with high mortality in women worldwide. Targeted nano-drug delivery system for breast cancer treatment has achieved encouraging results, because of increased drug concentration at the tumor site, thereby improving biocompatibility and blood half-life while reducing chemoresistance. However, the absence of available target on cancer cells is one of the major obstacles for triple-negative breast cancer (TNBC). Increasing studies have shown that heparanase (HPA) is highly expressed in many cancers, including TNBC. Thus paclitaxel(PTX) -encapsulated PEGylated PLGA nanoparticles were developed and further surface-functionalized with the HPA aptamers (Apt(S1.5)-PTX-NP). Moreover, targeting and cytotoxicity of Apt(S1.5)-PTX-NP to TNBC cells were evaluated with MDA-MB-231 as a model. These nanoparticles bonded to the HPA overexpressed on the surface of TNBC cells and were taken up by these cells, resulting in remarkably enhanced cellular toxicity compared with non-targeted PTX-NP that lack the HPA aptamer (P < 0.01). Furthermore, Apt(S1.5)-PTX-NP significantly exhibited enhanced anti-invasive and superior anti-angiogenesis activity compared with those of other experiment groups at low administration dosage. The Apt(S1.5)-PTX-NP demonstrated the most dramatic efficacy with the final mean tumor sizes of 157.30 ± 41.09 mm3 (mean ± SD; n = 10) in vivo treatment. Thus, the present study indicated that HPA is a promising target for drug delivery to TNBC cells, and nanoparticle-HPA-aptamer bioconjugates can provide new insights for TNBC treatment.”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

PLGA from PolySciTech used in development of liposome brain-cancer therapy

Monday, July 1, 2019, 4:36 PM ET

Treating brain cancer is not a trivial matter as even getting medicine across the blood-brain-barrier (BBB) is difficult. One method of crossing this barrier to treat cance is to rely on transferrin signaling. Recently, researchers from North Dakota State University used PLGA (AP022) from PolySciTech (www.polyscitech.com) as part of research into liposomal treatement of glioblastoma by using transferrin-penetratin to cross the BBB. This research holds promise to treat this often fatal disease. Read more: Lakkadwala, Sushant, Bruna dos Santos Rodrigues, Chengwen Sun, and Jagdish Singh. "Dual functionalized liposomes for efficient co-delivery of anti-cancer chemotherapeutics for the treatment of glioblastoma." Journal of Controlled Release (2019). https://www.sciencedirect.com/science/article/pii/S0168365919303669

“Highlights: Transferrin-Penetratin (Tf-Pen) liposomes were prepared by post-insertion method. Tf-Pen liposomes showed excellent biocompatibility for in vivo administration. Higher translocation of Tf-Pen liposomes across the co-culture endothelial barrier. Several fold increase in the concentration of anticancer drugs in mice brain. Increase in survival time and regression in glioblastoma tumor in mice brain. Abstract: Glioblastoma is a hostile brain tumor associated with high infiltration leading to poor prognosis. Anti-cancer chemotherapeutic agents have limited access into the brain due to the presence of the blood brain barrier (BBB). In this study, we designed a dual functionalized liposomal delivery system, surface modified with transferrin (Tf) for receptor mediated transcytosis and a cell penetrating peptide-penetratin (Pen) for enhanced cell penetration. We loaded doxorubicin and erlotinib into liposomes to enhance their translocation across the BBB to glioblastoma tumor. In vitro cytotoxicity and hemocompatibility studies demonstrated excellent biocompatibility for in vivo administration. Co-delivery of doxorubicin and erlotinib loaded Tf-Pen liposomes revealed significantly (p < 0.05) higher translocation (~15%) across the co-culture endothelial barrier resulting in regression of tumor in the in vitro brain tumor model. The biodistribution of Tf-Pen liposomes demonstrated ~12 and 3.3 fold increase in doxorubicin and erlotinib accumulation in mice brain, respectively compared to free drugs. In addition, Tf-Pen liposomes showed excellent antitumor efficacy by regressing ~90% of tumor in mice brain with significant increase in the median survival time (36 days) along with no toxicity. Thus, we believe that this study would have high impact for treating patients with glioblastoma.”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

mPEG-PLGA from PolySciTech used in development of nanoparticle-based treatment of brain-cancer

Thursday, June 27, 2019, 3:58 PM ET

Brain cancer is a fatal disease which is very difficult to treat. Notably, uptake to the brain from blood is very poor which prevents most pharmaceutical agents from being able to physically transport to the location of action. GSK461364A, a PlK1 inhibitor, has previously shown promise for inducing apoptosis of tumor cells. Recently, researchers at University of Massachusetts used mPEG-PLGA (AK027) and PLGA (AP041) from PolySciTech (www.polyscitech.com) to develop a nanoparticle delivery system for GSK461364A to brain cancer. This research holds promise to aid in treating this fatal disease. Read more: Velpurisiva, Praveena. "Engineering Nanomedicines for Combination Treatment of Glioblastoma Multiforme." PhD diss., University of Massachusetts Lowell, 2019. http://search.proquest.com/openview/49cd4046a581e02ea911132c4a6679ac/1?pq-origsite=gscholar&cbl=18750&diss=y

“Abstract (Abbreviated): This thesis delivers a novel combinatorial approach that is crucial to treat GBM. Patients often do not respond to higher doses of the same drug after prolonged exposure, since the tumors become refractory and develop new mutations due to tumor heterogeneity. Combination treatments are the key to address cancers, since the drugs target multiple molecular sites simultaneously and have a profound cytotoxic effect. Nanoparticles will enhance this action since they prevent non-specific targeting and enhance localization in the tumor due to enhanced permeability and retention effect. Nanomedicine increases the drug bioavailability and prevents the rapid drug degradation while avoiding over all drug exposure at once when administered into the body, thus reducing the toxic effects.”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

PLLA from PolySciTech Used in Research on Depot Delivery Systems for Alzheimer’s treatment.

Thursday, June 27, 2019, 3:57 PM ET

Rivastigmine is a reversible cholinesterase inhibitor used to treat Alzheimer’s or Parkinson’s disease. Since its location of action is in the brain and maintaining a controlled dose over time can enable better efficacy with minimal side effects, this drug would benefit from a controlled delivery system. Recently, researchers from North Dakota State University used PLA (AP047) from PolySciTech (www.polyscitech.com) as part of developing a Rivastigmine depot delivery system. This research holds promise to improve Alzheimer’s treatment. Read more: Lipp, Lindsey Dawn. "Evaluation of Smart Polymers for Controlled Release Delivery Systems." PhD diss., North Dakota State University, 2019. http://search.proquest.com/openview/f4049113c6e85e87a5b855ddf97e1000/1?pq-origsite=gscholar&cbl=18750&diss=y

“Abstract (Abbreviated ): Our goal was to develop a smart polymer, controlled release delivery system and evaluate its capabilities for use with salmon calcitonin and rivastigmine. Thermosensitive and phase sensitive smart polymers were evaluated for their potential as controlled release delivery systems. Thermosensitive triblock copolymers were synthesized with increasing lactide to glycolide ratios of 3.5:1, 4.5:1, and 5:1. Characterization was via analytical techniques including proton nuclear magnetic resonance, gel permeation chromatography, critical micellar concentration, sol-gel transition test tube inversion, and cellular biocompatibility assay. Only the 5:1 lactide to glycolide copolymer transitioned into gel at body temperature. Release duration in vitro was 70 days when salmon calcitonin was incorporated at 40% (w/v) in 5:1 thermosensitive copolymer while retaining the native conformation of salmon calcitonin as analyzed via micro bicinchioninic acid assay, circular dichroism, and differential scanning calorimetry. For phase sensitive polymer, we found the best formulation after optimization was that of 5% (w/v) 50:50 poly(lactic-co-glycolic acid) in 95:5 benzyl benzoate to benzyl alcohol with rivastigmine base incorporated at 216 mg/ml. Release was observed over the course of ~ 42 days. The results demonstrate that controlled release rivastigmine was accomplished and shows promise as a method to increase dosing interval and improve quality of life for those suffering from Alzheimer’s Disease.”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

PEG-PLGA and PLLA-NH2 from PolySciTech used in research on biological fate of nanomaterials

Thursday, June 27, 2019, 3:56 PM ET

If there is one thing the human body does very well, it is to attack and eliminate anything inside it which is perceived by the immune system as ‘non-self.’ As blood circulates through the human body, it is continuously cleansed by a series of natural clearance systems primarily the kidneys, spleen, and liver. Although this process is necessary to clean the blood of metabolic waste and toxins, it complicates drug-delivery as therapeutic agents and nanoparticle-based delivery systems are also cleared out of the blood stream often before they can achieve their desired therapeutic effect. Recently, researchers at University of Toronto and The Peter Gilgan Centre for Research & Learning (Canada) used mPEG-PLGA (AK037) and PLA-NH2 (AI032) from PolySciTech (www.polyscitech.com) to generate cyanine-5 (fluorescent dye) traceable nanoparticles for investigating particle clearance in-vivo. This research holds promise to improve the efficacy of nanoparticle-delivered medicines. Read more: Lazarovits, James, Shrey Sindhwani, Anthony James Tavares, Yuwei Zhang, Fayi Song, Julie Audet, Jonathan Robert Krieger, Abdullah Muhammad Syed, Benjamin Stordy, and Warren CW Chan. "Supervised Learning And Mass Spectrometry Predicts The In Vivo Fate Of Nanomaterials." ACS Nano (2019). https://pubs.acs.org/doi/abs/10.1021/acsnano.9b02774

“Abstract: The surface of nanoparticles changes immediately after intravenous injection because blood proteins adsorb on the surface. How this interface changes during circulation and its impact on nanoparticle distribution within the body is not understood. Here, we developed a workflow to show that the evolution of proteins on nanoparticle surfaces predicts the biological fate of nanoparticles in vivo. This workflow involves extracting nanoparticles at multiple time points from circulation, isolating the proteins off the surface and performing proteomic mass spectrometry. The mass spectrometry protein library served as inputs, while blood clearance and organ accumulation as outputs to train a supervised deep neural network that predicts nanoparticle biological fate. In a double-blinded study, we tested the network by predicting nanoparticle spleen and liver accumulation with upwards of 94% accuracy. Our neural network discovered that the mechanism of liver and spleen uptake is due to patterns of a multitude of nanoparticle surface adsorbed proteins. There are too many combinations to change these proteins manually using chemical or biological inhibitors to alter clearance. Therefore, we developed a technique that uses the host to act as a bioreactor to prepare nanoparticles with predictable clearance patterns that reduce liver and spleen uptake by 50% and 70% respectively. These techniques provide opportunities to both predict nanoparticle behaviour, and also to engineer surface chemistries that are specifically designed by the body. Keywords: nanoparticles, protein corona, mass spectrometry, neural networks, machine learning, artificial intelligence, predictive biology”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at http://bpcrconference.com

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.61140322685242 seconds)


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