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.


Select a topic to hide all other entries.
The most recent item is at the top.

PLGA from PolySciTech used in development of nanoparticle vaccine delivery system to prevent Johne’s disease in cattle

Wednesday, April 24, 2019, 1:33 PM ET

In addition to human applications, PLGA from PolySciTech is also used in veterinary uses. Johne’s disease, caused by Mycobacterium avium subspecies paratuberculosis, is a contagious, chronic, and usually fatal infection that affects primarily the small intestine of ruminants. Killing this bacteria is difficult and this contagious disease can spread rapidly through a herd with devastating financial effects to farmers as well as reducing the overall food supply. Recently, researchers at Washington State University, US Department of Agriculture, Alexandria University (Egypt), Egyptian Ministry of Agriculture, and Inje University (Korea) utilized PLGA (AP054) from PolySciTech (www.polyscitech.com) to create vaccine-loaded nanoparticles for prevention of Johne’s disease. This research holds promise to prevent this rapidly spreading and fatal disease from affecting cattle and improve food sustainability and security. Read more: Abdellrazeq, Gaber S., Mahmoud M. Elnaggar, John P. Bannantine, David A. Schneider, Cleverson D. Souza, Julianne Hwang, Asmaa HA Mahmoud et al. "A peptide-based vaccine for Mycobacterium avium subspecies paratuberculosis." Vaccine (2019). https://www.sciencedirect.com/science/article/pii/S0264410X19305043

“Highlights: A M. a. sbsp. paratuberculosis membrane protein elicits CD8 T cells that kill intracellular Map. Incorporation of MMP into a nanoparticle (NP) vector enhances intracellular killing of Map. Intracellular killing of M. a. sbsp. paratuberculosis is mediated by CD8 T cells.Abstract: Recent efforts to develop a live attenuated vaccine against Mycobacterium avium subsp. paratuberculosis (Map), the causative agent of Johne’s disease (JD), revealed relA is important in Map virulence. Deletion of the relA gene impairs the ability of Map to establish a persistent infection. Analysis of the basis for this observation revealed infection with a relA deletion mutant (ΔrelA) elicits development of cytotoxic CD8 T cells (CTL) with the ability to kill intracellular bacteria. Further analysis of the recall response elicited by ΔrelA vaccination showed a 35 kDa membrane peptide (MMP) is one of the targets of the immune response, suggesting it might be possible to develop a peptide-based vaccine based on MMP. To explore this possibility, ex vivo vaccination studies were conducted with MMP alone and incorporated into a nanoparticle (NP) vector comprised of poly (D, L-lactide-co-glycolide) and monophosphoryl lipid A (PLGA/MPLA). As reported, ex vivo vaccination studies showed CD8 CTL were elicited with classic and monocyte derived dendritic cells (cDC and MoDC) pulsed with MMP alone and incorporated into a PGLA/MPLA vector. Incorporation of MMP into a NP vector enhanced the ability of CD8 CTL to kill intracellular bacteria. The findings indicate incorporation of MMP into a PGLA/MPLA nanoparticle vector is one of the possible ways to develop a MMP based vaccine for Johne’s disease. Keywords: Zoonotic pathogen Mycobacterium avium subspecies paratuberculosis Propidium monoazide Flow cytometry Intracellular killing Monocyte derived dendritic cells Cytotoxic T cells Bovine”

-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 www.bpcrconference.com

BPCR News Release

Thursday, April 18, 2019, 3:21 PM ET


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 www.bpcrconference.com

P(DL)La-PEG-COOH and mPEG-PLA from PolySciTech used in development of antibacterial-nanovesicles to treat MRSA

Thursday, April 18, 2019, 2:45 PM ET

Typical staphylococcus aureus (Staph) is an extremely common bacterial present on skin and hair in up to 25 percent of healthy people. Typical Staph is easily treated with conventional antibiotics, however Methicillin-Resistant Staphylococcus aureus (MRSA) is an antibiotic resistant strain that has evolved to be difficult to treat. Conventional therapies work poorly against this kind of bacterial infection and these often require advanced solutions to prevent the spread of the difficult-to-kill bacteria. Recently, researchers at Northeastern University used PLA-PEG-COOH (AI023) and mPEG-PLA (AK021) from PolySciTech (www.polyscitech.com) to develop bacteria-killing nanovesicles to treat MRSA. This research holds promise to provide for treatment against this difficult to treat bacterial infection. Read more: Bassous, Nicole J., and Thomas J. Webster. "The Binary Effect on Methicillin‐Resistant Staphylococcus aureus of Polymeric Nanovesicles Appended by Proline‐Rich Amino Acid Sequences and Inorganic Nanoparticles." Small (2019): 1804247. https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.201804247

“Abstract: Prevalent research underscores efforts to engineer highly sophisticated nanovesicles that are functionalized to combat antibiotic‐resistant bacterial infections, especially those caused by methicillin‐resistant Staphylococcus aureus (MRSA), and that aid with wound healing or immunomodulation. This is especially relevant for patients who are susceptible to Staphylococcus aureus infections postoperatively. Here, antibacterial formulations are incorporated into polymeric, biocompatible vesicles called polymersomes (PsNPs) that self‐assemble via hydrophobic interactions of admixed aqueous and organic substances. Nano‐PsNPs are synthesized using a high molecular weight amphiphilic block copolymer, and are conjugated to include antimicrobial peptides (AMPs) along the peripheral hydrophilic region and silver nanoparticles (AgNPs) inside their hydrophobic corona. In vitro testing on bacterial and human cell lines indicates that finely tuned treatment concentrations of AMP and AgNPs in PsNPs synergistically inhibits the growth of MRSA without posing significant side effects, as compared with other potent treatment strategies. A ratio of silver‐to‐AMP of about 1:5.8 corresponding to ≈11.6 µg mL−1 of silver nanoparticles and 14.3 × 10−6 m of the peptide, yields complete MRSA inhibition over a 23 h time frame. This bacteriostatic activity, coupled with nominal cytotoxicity toward native human dermal fibroblast cells, extends the potential for AMP/AgNP polymersome therapies to replace antibiotics in the clinical setting.”

-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 www.bpcrconference.com

Block-copolymers from PolySciTech used in development of Adapalene-nanoparticle delivery system to cross the blood-brain-barrier

Thursday, April 18, 2019, 2:43 PM ET

“Drugs don’t deliver themselves” is a statement which has multiple meanings depending on who you are talking to. For retinoid molecules, drug-delivery to brain tissue is not a simple task as these highly-effective therapeutics are also highly water insoluble. Furthermore, the brain has extremely selective uptake of molecules across the ‘blood-brain-barrier’ which means any attempt to deliver a medicinal molecule to the brain will require getting the molecule across this barrier so that it can have therapeutic efficacy. Recently, researchers at Barrow Neurological Institute and University of Texas Health Science Center at Houston used PCL (AP108) and mPEG-PLA (AK054) from PolySciTech (www.polyscitech.com) to create adapalene loaded nanoparticles for brain-delivery. This research holds promise to provide for improved therapy against a variety of neurological diseases. Read more: Medina, David X., Eugene P. Chung, Robert Bowser, and Rachael W. Sirianni. "Lipid and polymer blended polyester nanoparticles loaded with adapalene for activation of retinoid signaling in the CNS following intravenous administration." Journal of Drug Delivery Science and Technology (2019). https://www.sciencedirect.com/science/article/pii/S1773224719300358

“Abstract: Small molecule retinoids are potential therapeutics for a variety of neurological diseases. However, most retinoids are poorly water soluble and difficult to deliver in vivo, which prevents further study of their utility to treat disease. Here, we focus on adapalene, an FDA approved drug that is a specific agonist for the retinoic acid receptor β (RARβ). We sought to develop nanoparticle delivery systems that would enable effective drug delivery to the CNS. We developed strategies to produce nanoparticles based on the hypothesis that incorporation of hydrophobic molecules into a polyester base would improve adapalene loading. In the first scheme, poly (lactic acid)-poly (ethylene glycol) (PLA-PEG) was blended with low molecular weight poly (lactic acid) (PLA) or poly (caprolactone) (PCL). In the second scheme, poly (lactic-co-glycolic acid) (PLGA) was blended with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol) (DSPE-PEG). Our data demonstrate that blending low molecular weight polyesters or DSPE-PEG into the primary nanoparticle base improves encapsulation of adapalene, presumably by enhancing adapalene solubility in the nanoparticle. Peripheral administration of these nanoparticles activated retinoid signaling in the brain and spinal cord of healthy mice. These studies provide new approaches for nanoparticle fabrication and establish proof of principle that systemically administered, adapalene-loaded nanoparticles activate retinoid signaling in the CNS.”

-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 www.bpcrconference.com

PLLA-PEG-Mal and PLGA-Rhodamine from PolySciTech used in development of tumor-seeking nanoparticle-laden stem-cell drug delivery system for treatment of cancer.

Friday, April 12, 2019, 2:59 PM ET

Cancer is unlike other diseases in that it is not caused by an invasion from a foreign pathogen (such as bacterial or viral infection). The inherent difficulty with its treatment is that, since cancer is comprised of cells similar to that of the patient’s own cells, most therapies which are applied to kill the cancer also harm the patient. This lack of specificity is the main cause of side-effects from chemotherapy (hair-loss, naseua, weakness, etc.). One mechanism to deal with this is to design a delivery system which will ensure that the bulk of the cancer treatment goes to the site of the tumor. Recently, researchers at University of Minnesota and Breck School utilized PLGA-rhodamine (AV011) and PLLA-PEG-Mal (AI119 ) from PolySciTech (www.polyscitech.com) to develop TAT functionalized nanoparticles for uptake into MSC’s to deliver to tumors. This research holds promise to provide for improved treatments of cancer. Read more: Moku, Gopikrishna, Buddhadev Layek, Lana Trautman, Samuel Putnam, Jayanth Panyam, and Swayam Prabha. "Improving Payload Capacity and Anti-Tumor Efficacy of Mesenchymal Stem Cells Using TAT Peptide Functionalized Polymeric Nanoparticles." Cancers 11, no. 4 (2019): 491. https://www.mdpi.com/2072-6694/11/4/491

“Abstract: Mesenchymal stem cells (MSCs) accumulate specifically in both primary tumors and metastases following systemic administration. However, the poor payload capacity of MSCs limits their use in small molecule drug delivery. To improve drug payload in MSCs, we explored polymeric nanoparticles that were functionalized with transactivator of transcription (TAT) peptide. Paclitaxel loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles (15–16% w/w paclitaxel; diameter of 225 ± 7 nm; and zeta potential of −15 ± 4 mV) were fabricated by emulsion-solvent evaporation method, followed by TAT-conjugation to the surface of nanoparticles via maleimide-thiol chemistry. Our studies demonstrated that TAT functionalization improved the intracellular accumulation and retention of nanoparticles in MSCs. Further, nano-engineering of MSCs did not alter the migration and differentiation potential of MSCs. Treatment with nano-engineered MSCs resulted in significant (p < 0.05) inhibition of tumor growth and improved survival (p < 0.0001) in a mouse orthotopic model of lung cancer compared to that with free or nanoparticle encapsulated drug. In summary, our results demonstrated that MSCs engineered using TAT functionalized nanoparticles serve as an efficient carrier for tumor specific delivery of anticancer drugs, resulting in greatly improved therapeutic efficacy. Keywords: mesenchymal stem cells (MSCs); TAT peptide; PLGA; paclitaxel; nano-engineered MSCs; orthotopic lung tumor model”

-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 www.bpcrconference.com

PLGA-PEG-PLGA from PolySciTech used in development of Propranolol delivery system for treatment of hemangioma

Friday, April 12, 2019, 2:56 PM ET

Hemangioma’s are a common form of a birth mark consisting of an area with an excess of blood-vessels. In the case of superficial surface hemangioma’s there may be no need for treatment as these are benign and heal over time. However, hemangioma’s can occur anywhere and if they are present in certain internal organs (for example brain or liver) or if they interfere with vision or breathing, they can be serious. Recently, researchers at Zhengzhou University (China) used PLGA-PEG-PLGA (AK016) from PolySciTech (www.polyscitech.com) to create propranolol loaded drug-delivery particles. This research holds promise to provide for improved therapy against hemangiomas. Read more: Guo, Xiaonan, Changxian Dong, Qiuyu Liu, Xiaoshuang Zhu, Song Zuo, and Hongyu Zhang. "The sustained and targeted treatment of hemangiomas by propranolol-loaded CD133 aptamers conjugated liposomes-in-microspheres." Biomedicine & Pharmacotherapy 114 (2019): 108823. https://www.sciencedirect.com/science/article/pii/S0753332219306535

“Highlights: Propranolol-loaded CD133 aptamers conjugated liposomes-in-microspheres (PCLIM) realized sustained therapy of hemangiomas. PCLIM could inhibit the proliferation of HemSCs and expression of VEGF and bFGF in HemSCs. PCLIM could realize the targeted therapy of hemangiomas by targeting CD133-positive hemangioma-derived stem cells. Abstract: We previously developed propranolol-encapsulated liposomes-in-microspheres (PLIM) to realize the sustained propranolol release for the treatment of hemangiomas. However, the liposomes released from the microspheres still lacked specificity for CD133-positive hemangioma-derived stem cells (HemSCs) which are considered to be the seeds of hemangiomas. Therefore, we hereby encapsulated propranolol-loaded CD133 aptamers conjugated liposomes in poly(lactic-co-glycolic acid (PLGA) microspheres to develop propranolol-loaded CD133 aptamers conjugated liposomes-in-microspheres (PCLIM), to realize the aim of the sustained and targeted therapy of hemangiomas. The evaluation of the release of propranolol from PCLIM was carried out, and the cytotoxic effect and angiogenic growth factor expression inhibitory ability of PCLIM were performed in HemSCs. The in vivo hemangioma inhibitory ability of PCLIM was also investigated in nude mice with subcutaneous human hemangiomas. PCLIM possessed a desired size of 29.2 μm, drug encapsulation efficiency (25.3%), and a prolonged drug release for 40 days. Importantly, PCLIM could inhibit HemSCs proliferation and the protein expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor-A (VEGF) in HemSCs to a greater extent compared with PLIM. In nude mice bearing hemangioma xenograft, PCLIM showed the best therapeutic efficacy towards hemangiomas, as reflected by remarkably decreased hemangioma volume, weight and microvessel density (MVD). Thus, our results demonstrated that PCLIM realized the sustained and targeted treatment of hemangiomas, resulting in remarkable inhibition of hemangiomas. Keywords: CD133 Hemangiomas Propranolol Liposomes Microspheres 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 www.bpcrconference.com

PLGA-PEG-COOH from PolySciTech used in development of nanoparticle-based anticoagulant (Alteplase) delivery system for treatment of blood clotting

Thursday, April 11, 2019, 2:39 PM ET

The formation of blood-clots within the human blood system is part of several severe diseases including heart-attack and stroke. Alteplase is a is a tissue plasminogen activator which acts to break up these clots. To improve the efficiency and specificity of this action, the Alteplase can be encapsulated in nanoparticles decorated with a plaque-homing peptide, CREKA, which binds to fibrin-fibronectin clots and accumulates at the surface of plaques. Recently, Researchers at Universidad de Sevilla (Spain) used PLGA-PEG-COOH (AI034) from PolySciTech (www.polyscitech.com) to develop drug-delivery nanoparticles carrying Alteplase. This research holds promise to provide for improved treatments of diseases associated with clotting such as stroke and heart-attacks. Read more: Fernández Pérez, Irene. "Estudio preliminar de una formulación de Nanoparticulaspara targetactivo de un." Thesis Presentation Universidad de Sevilla (2018). https://idus.us.es/xmlui/bitstream/handle/11441/82199/Irene%20Fern%C3%A1ndez%20P%C3%A9rez.pdf?sequence=1

“Abstract [*translated*]: The present work fits into the currently emerging field of nanomedicine. Specifically, it is a preliminary study based in the design and development of nanoparticles that will serve as a system of administration of a fibrinolytic drug, which is intended to actively address the pathological thrombi formed by the process of blood coagulation. To do this, several batches of PLGA nanoparticles have been synthesized using different polymers (Resomer® 504H and PLGA-PEG) and varying amounts/concentration of drug (Actilyse®). Nanoparticle synthesis has been carried out by the double emulsion method with evaporation of solvent, obtaining particles of an adequate nanometric size (~ 200 - 300 nm) with narrow size distribution and negative zeta potential. The tests carried out on the efficacy of drug encapsulation presented good results. The maximum loading efficiency (97%) was observed for PLGA-PEG particles loaded at 5% w / w (active / polymer). To carry out the preliminary study of the design of these nanoparticles for the targeting of clots, the CREKA pentapeptide was used for surface functionalization of the particles. This enables a process of bioconjugation. This lead to a slight increase in the average size of the particles and in the PdI values. The surface load data obtained showed a potentially better conjugation efficiency for the PLGA-PEG particles. However, this bioconjugation data is very preliminary.”

-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 www.bpcrconference.com

PolySciTech PLGA used in development of magnetic nanoparticles for breast-cancer therapy

Tuesday, April 9, 2019, 3:33 PM ET

There are many ways to control motion of nanoparticles in a living body including both active and passive targeting. Another method is to generate nanoparticles which respond to an external stimulus such as magnetism which can be used to draw nanoparticles into a target region of the body near a tumor. Recently, Researchers at Purdue University used PLGA (AP020) From PolySciTech (www.polyscitech.com) to develop paclitaxel-loaded nanoparticles and tested these for their effects on breast cancer. This research holds promise to provide for improved therapies against this form of cancer. Read more: Park, Jinho, Joonyoung Park, Mark A. Castanares, David S. Collins, and Yoon Yeo. "Magnetophoretic delivery of a tumor priming agent for chemotherapy of metastatic murine breast cancer." Molecular pharmaceutics (2019). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.8b01148

“Tumor microenvironment (TME) is a significant physical barrier to effective delivery of chemotherapy into solid tumors. To overcome this challenge, tumors are pre-treated with an agent that reduces cellular and extracellular matrix densities prior to chemotherapy. However, it also comes with a concern that metastasis may increase due to the loss of protective containment. We hypothesize that timely priming at the early stage of primary tumors will help control metastasis. To test this, we primed orthotopic 4T1 breast tumors with a paclitaxel (PTX)-loaded iron oxide decorated poly(lactic-co-glycolic acid) nanoparticle composite (PTX@PINC), which can be quickly concentrated in target tissues with the aid of an external magnet, and monitored its effect on the delivery of subsequently administered NPs. Magnetic resonance imaging and optical whole-body imaging confirmed that PTX@PINC was efficiently delivered to tumors by the external magnet and help loosen the tumors to accommodate subsequently-delivered NPs. Consistently, the primed tumors responded to Doxil better than non-primed tumors. In addition, lung metastasis was significantly reduced in the animals PINC-primed prior to Doxil administration. These results support that PINC combined with magnetophoresis can facilitate timely management of primary tumors with a favorable secondary effect on metastasis.”

-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 www.bpcrconference.com

Fluorescent PLGA from PolySciTech used in development of wearable biomedical sensing system

Tuesday, April 9, 2019, 3:32 PM ET

For chronic illness and other applications the convenience and ease of a wearable device (such as a transdermal patch or a wrist-watch type device) provides for several advantages over continuous monitoring and manual medicinal administrations. Recently, researchers at Griffith University, Berghofer Medical Research Institute, and University of South Australia, used fluorescent PLGA-AF488 (custom-made) from PolySciTech (www.polyscitech.com) as part of a wearable smart-device to control drug delivery in response to changes in mechanical forces such as changes in pulse or other factors. This research holds promise for the development of devices for use in a wide array of disease states. Read more: Shi, Ge, Tianqing Liu, Zlatko Kopecki, Allison Cowin, Ivan Lee, Jing-Hong Pai, Sean E. Lowe, and Yu Lin Zhong. "A Multifunctional Wearable Device with a Graphene/Silver Nanowire Nanocomposite for Highly Sensitive Strain Sensing and Drug Delivery." Journal of Carbon Research C 5, no. 2 (2019): 17. https://www.mdpi.com/2311-5629/5/2/17

“Abstract: Advances in wearable, highly sensitive and multifunctional strain sensors open up new opportunities for the development of wearable human interface devices for various applications such as health monitoring, smart robotics and wearable therapy. Herein, we present a simple and cost-effective method to fabricate a multifunctional strain sensor consisting of a skin-mountable dry adhesive substrate, a robust sensing component and a transdermal drug delivery system. The sensor has high piezoresisitivity to monitor real-time signals from finger bending to ulnar pulse. A transdermal drug delivery system consisting of polylactic-co-glycolic acid nanoparticles and a chitosan matrix is integrated into the sensor and is able to release the nanoparticles into the stratum corneum at a depth of ~60 m. Our approach to the design of multifunctional strain sensors will lead to the development of cost-effective and well-integrated multifunctional wearable devices. Keywords: graphene; silver nanowire; multifunctional; wearable; strain sensor; drug delivery”

-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 www.bpcrconference.com

Poly(lactide)-diacrylate from PolySciTech used in patent describing development of advanced assay method

Tuesday, April 9, 2019, 3:31 PM ET

The ability to rapidly and accurately diagnose a disease state in a patient is critical as this guides the subsequent routes of treatment. A recent patent by Selux Diagnostics Inc. describes the use of PLA-diacrylate (AI036) from PolySciTech (www.polyscitech.com) to develop particles for assay applications. This research holds promise for improved assay methodologies across a wide array of applications including diagnostic applications. Read more: Stern, Eric, Aleksandar Vacic, Alec Nathanson Flyer, Benjamin Spears, and Susan Clardy. "Dissociable nanoparticles with inter alia transition-metal complex catalysts." U.S. Patent Application 15/745,361, filed March 28, 2019. https://patents.google.com/patent/US20190091673A1/en

“Abstract: Nanoparticles for use in assay methods for detecting analytes in samples, which comprise a signal inducing agent, e.g. a transition-metal catalyst or a chemiluminophore, a chemiluminophore precursor, a soluble absorber, or a soluble absorber precursor. After binding to an analyte, the nanoparticle is dissociated by a chemical or physical trigger, e.g. an organic solvent or ultrasound, to release the signal inducing agent, which releases a detectable signal via a physical or chemical reaction. The nanoparticles comprising a chemiluminophore, a chemiluminophore precursor, a soluble absorber, or a soluble absorber precursor can also effect chemical reactions that serve as signal amplifiers.”

-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 www.bpcrconference.com

PEG-block copolymers from PolySciTech used in development of ultra-sound triggered nanoparticles for localized drug delivery

Thursday, March 28, 2019, 1:37 PM ET

The same molecule which operates as a medicine in one part of the body may be highly toxic in another part of the body. For this reason, the ability to control the delivery of a molecule to a very specific area is highly preferential for a wide variety of diseases. One means to do this is to introduce the medicinal molecule in a bound form and then externally trigger it by a specific mechanism so that it is only unbound in a specific region. Recently, researchers from Stanford University, University of California, Massachusetts Institute of Technology, and Massachusetts General Hospital used mPEG-PLGA, mPEG-PLA, and mPEG-PCL (AK073, AK001, AK003, AK004, AK052, AK090) from PolySciTech (www.polyscitech.com) to generate ultra-sound triggered nanoparticles. This research holds promise to provide for localized drug delivery. As a side-note, co-author Ananya Karthik, a high-school student and Regeneron Science Talent Search finalist, qualifies as one of the youngest scientists to ever author a paper utilizing PolySciTech polymers. Read more: Zhong, Qian, Byung C. Yoon, M. Aryal, Jeffrey B. Wang, T. Ilovitsh, M. A. Baikoghli, N. Hosseini-Nassab, A. Karthik, R.H. Cheng, K.W. Ferrara, R.D. Airan "Polymeric perfluorocarbon nanoemulsions are ultrasound-activated wireless drug infusion catheters." Biomaterials (2019). https://www.sciencedirect.com/science/article/pii/S0142961219301656

“Abstract: Catheter-based intra-arterial drug therapies have proven effective for a range of oncologic, neurologic, and cardiovascular applications. However, these procedures are limited by their invasiveness and relatively broad drug spatial distribution. The ideal technique for local pharmacotherapy would be noninvasive and would flexibly deliver a given drug to any region of the body with high spatial and temporal precision. Combining polymeric perfluorocarbon nanoemulsions with existent clinical focused ultrasound systems could in principle meet these needs, but it has not been clear whether these nanoparticles could provide the necessary drug loading, stability, and generalizability across a range of drugs, beyond a few niche applications. Here, we develop polymeric perfluorocarbon nanoemulsions into a generalized platform for ultrasound-targeted delivery of hydrophobic drugs with high potential for clinical translation. We demonstrate that a wide variety of drugs may be effectively uncaged with ultrasound using these nanoparticles, with drug loading increasing with hydrophobicity. We also set the stage for clinical translation by delineating production protocols that are scalable and yield sterile, stable, and optimized ultrasound-activated drug-loaded nanoemulsions. Finally, we exhibit a new potential application of these nanoemulsions for local control of vascular tone. This work establishes the power of polymeric perfluorocarbon nanoemulsions as a clinically-translatable platform for efficacious, noninvasive, and localized ultrasonic drug uncaging for myriad targets in the brain and body. Keywords: Focused ultrasound Clinically translatable Targeted drug delivery Noninvasive ultrasonic drug uncaging Drug delivery platform Spatiotemporally controlled 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 www.bpcrconference.com

PLGA from PolySciTech used in Patent Describing Complex Microdevice Manufacture

Thursday, March 28, 2019, 1:35 PM ET

Manufacturing techniques are constantly in a state of development and there have been several recent advances in development of construction of very small and very complicated parts. Often such parts are too miniscule in size for conventional machining techniques to be of much use which requires innovation in manufacturing techniques. Recently, researchers from Massachusetts Institute of Technology used PLGA (AP045) from PolySciTech (www.polyscitech.com) as part of their patent application for complex microdevices created by a combination of photolithography and micromachining techniques. This research could be used to generated a wide array of microdevices for biomedical applications. Read more: Mchugh, Kevin, Ana Jaklenec, and Robert S. Langer. "Microdevices With Complex Geometries." U.S. Patent Application 16/130,368, filed March 14, 2019. http://www.freepatentsonline.com/y2019/0076631.html

“Abstract: Microdevices with complex three-dimensional (3D) internal and external structures are described. The microdevices are made by a method combining micromolding and soft lithography with an aligned sintering process. The microfabrication method, termed StampEd Assembly of polymer Layers (SEAL), generates microdevices with complex geometries and with fully-enclosed internal cavities containing a solid or liquid. The microdevices are useful for biomedical, electromechanical, energy and environmental applications.”

-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 www.bpcrconference.com

mPEG-PLGA/PLGA from PolySciTech used in development of dual-drug loaded nanoparticle-based brain-cancer therapy

Thursday, March 21, 2019, 4:16 PM ET

Glioblastoma is a form of brain cancer in which malignant glial cells spread to various areas of the brain. This form of cancer is very difficult to treat and requires specific manipulations of the biochemistry of the malignant cells to kill them. Gefitinib acts to dephosphorylate Bcl-2 associated death promoter (BAD) and GSK461364A induces cell cycle arrest at G2/M phase. Both of these mechanisms lead to apoptosis (cell death) and together these drugs can act synergistically to be potent treatment against cancer. Recently, researchers at University of Massachusetts Lowell utilized mPEG-PLGA (AK027) and PLGA (AP023) from PolySciTech (www.polyscitech.com) to create dual-loaded nanoparticles and tested these for use as a treatment against glioblastoma. This research holds promise to provide new therapeutic options against this lethal form of cancer. Read more: Velpurisiva, Praveena, and Prakash Rai. "Synergistic Action of Gefitinib and GSK41364A Simultaneously Loaded in Ratiometrically-Engineered Polymeric Nanoparticles for Glioblastoma Multiforme." Journal of Clinical Medicine 8, no. 3 (2019): 367. https://www.mdpi.com/2077-0383/8/3/367

“Abstract: Glioblastoma Multiforme is a deadly cancer of glial cells with very low survival rates. Current treatment options are invasive and have serious side effects. Single drug treatments make the tumor refractory after a certain period. Combination therapies have shown improvements in treatment responses against aggressive forms of cancer and are becoming a mainstay in the management of cancer. The purpose of this study is to design a combinatorial treatment regimen by engineering desired ratios of two different small molecule drugs (gefitinib and GSK461364A) in a single carrier that can reduce off-target effects and increase their bioavailability. Synergistic effects were observed with our formulation when optimal ratios of gefitinib and GSK461364A were loaded in poly (lactic-co-glycolic) acid and polyethylene glycol (PLGA-PEG) nanoparticles and tested for efficacy in U87-malignant glioma (U87-MG) cells. Combination nanoparticles proved to be more effective compared to single drug encapsulated nanoparticles, free drug combinations, and the mixture of two single loaded nanoparticles, with statistically significant values at certain ratios and drug concentrations. We also observed drastically reduced clonogenic potential of the cells that were treated with free drugs and nanoparticle combinations in a colony forming assay. From our findings, we conclude that the combination of GSK461364A and higher concentrations of gefitinib when encapsulated in nanoparticles yield synergistic killing of glioma cells. This study could form the basis for designing new combination treatments using nanoparticles to deliver multiple drugs to cancer cells for synergistic effects. Keywords: combination therapy; cancer; glioblastoma multiforme; polymeric nanoparticles; gefitinib; GSK461364A; drug resistance; synergistic effect; drug interaction; enhanced permeation and retention”

-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 www.bpcrconference.com

Manuscript “Complex Sameness” From Akina, Inc.-FDA Research Highlights Q1/Q2 Assay Methodologies

Monday, March 18, 2019, 4:11 PM ET

In addition to providing polymer products through the PolySciTech product line, Akina, Inc. also provides analytical and research services through the Akinalytics division (http://www.akinalytics.com/). A recent publication relates the development work performed with the Food and Drug Administration to deconstruct microparticle formulations which are constructed of more than one type of PLGA (varying lactide ratio) by applying a series of semi-solvents which dissolve higher-lactide content PLGA sequentially so each fraction can be assayed. Trelstar ® 22.5 mg dose was deconstructed by this method and each fraction was assayed. This research holds promise to develop assays which enable determination of sameness between Reference-Listed Drug (RLD) and a proposed generic. Read more: Skidmore, Sarah, Justin Hadar, John Garner, Haesun Park, Kinam Park, Yan Wang, and Xiaohui Jiang. “Complex sameness: Separation of mixed poly (lactide-co-glycolide) s based on the lactide: glycolide ratio.” Journal of Controlled Release (2019). https://doi.org/10.1016/j.jconrel.2019.03.002 [Link for 50-Days of Free access (May 5, 2019): https://authors.elsevier.com/c/1YjxgcI2~p~xz]

“Abstract: Poly (lactide-co-glycolide) (PLGA) has been used for making injectable, long-acting depot formulations for the last three decades. An in depth understanding of PLGA polymers is critical for development of depot formulations as their properties control drug release kinetics. To date, about 20 PLGA-based formulations have been approved by the U.S. Food and Drug Administration (FDA) through new drug applications, and none of them have generic counterparts on the market yet. The lack of generic PLGA products is partly due to difficulties in reverse engineering. A generic injectable PLGA product is required to establish qualitative and quantitative (Q1/Q2) sameness of PLGA to that of a reference listed drug (RLD) to obtain an approval from the FDA. Conventional characterizations of PLGA used in a formulation rely on measuring the molecular weight by gel permeation chromatography (GPC) based on polystyrene molecular weight standards, and determining the lactide:glycolide (L: G) ratio by 1H NMR and the end-group by 13C NMR. These approaches, however, may not be suitable or sufficient, if a formulation has more than one type of PLGA, especially when they have similar molecular weights, but different L:G ratios. Accordingly, there is a need to develop new assay methods for separating PLGAs possessing different L:G ratios when used in a drug product and characterizing individual PLGAs. The current work identifies a series of semi-solvents which exhibit varying degrees of PLGA solubility depending on the L:G ratio of the polymer. A good solvent dissolves PLGAs with all L:G ratios ranging from 50:50 to 100:0. A semi-solvent dissolves PLGAs with only certain L:G ratios. Almost all semi-solvents identified in this study increase their PLGA solubility as the L:G ratio increases, i.e., the lactide content increases. This lacto-selectivity, favoring higher L:G ratios, has been applied for separating individual PLGAs in a given depot formulation, leading to analysis of each type of PLGA. This semi-solvent method allows a simple, practical bench-top separation of PLGAs of varying L:G ratios. This method enables isolation and identification of individual PLGAs from a complex mixture that is critical for the quality control of PLGA formulations, as well as reverse engineering for generic products to establish the Q1/Q2 sameness. Keywords: PLGA separation L:G ratio Trelstar Q1/Q2 sameness Long-acting depot”

PLGA-Rhodamine/PLGA from PolySciTech used in development of peptide-targeted nanoparticles to macrophages for cancer therapy

Monday, March 18, 2019, 11:46 AM ET

Cancer is not a homogenous mass of cells, rather it is a complex mixture of microenvironment and tissue. Several factors of the microenvironment act to promote the growth of the cancer tumor. One of these is the presence of tumor-associated macrophages (immune cells) which promote the growth of cancer cells by suppressing the local immune system as well as by other mechanisms. One target for cancer therapy is to prevent the mechanisms of these support cells thereby leaving cancer more vulnerable and reducing its growth and survival. Recently, researchers at Purdue University and Soochow University (China) used PLGA (AP031) and fluorescent PLGA-Rhodamine (AV011) from PolySciTech (www.polyscitec.com) to develop peptide-bound nanoparticles with selective uptake towards these macrophages. The fluorescent PLGA enables tracking the location of the nanoparticles as a means to confirm uptake. This research holds promise for the development of powerful and selective therapies against cancer. Read more: Pang, Liang, Yihua Pei, Gozde Uzunalli, Hyesun Hyun, L. Tiffany Lyle, and Yoon Yeo. "Surface Modification of Polymeric Nanoparticles with M2pep Peptide for Drug Delivery to Tumor-Associated Macrophages." Pharmaceutical Research 36, no. 4 (2019): 65. https://link.springer.com/article/10.1007/s11095-019-2596-5

“Purpose: Tumor-associated macrophages (TAMs) with immune-suppressive M2-like phenotype constitute a significant part of tumor and support its growth, thus making an attractive therapeutic target for cancer therapy. To improve the delivery of drugs that control the survival and/or functions of TAMs, we developed nanoparticulate drug carriers with high affinity for TAMs. Methods: Poly(lactic-co-glycolic acid) nanoparticles were coated with M2pep, a peptide ligand selectively binding to M2-polarized macrophages, via a simple surface modification method based on tannic acid-iron complex. The interactions of M2pep-coated nanoparticles with macrophages of different phenotypes were tested in vitro and in vivo. PLX3397, an inhibitor of the colony stimulating factor-1 (CSF-1)/CSF-1 receptor (CSF-1R) pathway and macrophage survival, was delivered to B16F10 tumors via M2pep-modified PLGA nanoparticles. Results: In bone marrow-derived macrophages polarized to M2 phenotype, M2pep-coated nanoparticles showed greater cellular uptake than those without M2pep. Consistently, M2pep-coated nanoparticles showed relatively high localization of CD206+ macrophages in B16F10 tumors. PLX3397 encapsulated in M2pep-coated nanoparticles attenuated tumor growth better than the free drug counterpart. Conclusion: These results support that M2pep-coating can help nanoparticles to interact with M2-like TAMs and facilitate the delivery of drugs that control the tumor-supportive functions of TAMs. KEY WORDS: Drug delivery M2pep PLGA nanoparticles PLX3397 tumor-associated macrophages”

-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 www.bpcrconference.com

Thermogelling PLGA-PEG-PLGA from PolySciTech used in research of healing/scar-formation of cardiovascular tissue

Friday, March 15, 2019, 1:44 PM ET

The formation of scar tissue, or fibrosis, is a common response to injury and is part of the healing process of most tissues. Superficial scarring is benign however when it occurs in critical areas (such as cardiovascular tissue post balloon angioplasty) it can be lethal. Recently, researchers at The Ohio State University and University of Wisconsin used thermogelling PLGA-PEG-PLGA (AK012) from PolySciTech (www.polyscitech.com) to deliver centrinone-B (a PLK4 inhibitor) as part of modeling the effect that blocking PLK4 had on healing and scar formation. This research holds promise to aid in developing therapeutics to improve cardiovascular healing as part of treatment of atherosclerosis and hypertension. Read more: Jing Li, Go Urabe, Mengxue Zhang, Yitao Huang, Bowen Wang, Lynn Marcho, Hongtao Shen, K. Craig Kent, Lian-Wang Guo “A non-canonical role of polo-like kinase-4 in adventitial fibroblast cell type transition” bioRxiv (2019) 570267; doi: https://doi.org/10.1101/570267

“Abstract: Fibroblast-to-myofibroblast transition (FMT) is central to fibrosis. A divergent member of the polo-like kinase family, PLK4 is known for its canonical role in centriole duplication. Whether this mitotic factor regulates cell type transitions was underexplored. Here we investigated PLK4’s activation and expression and regulations thereof in platelet-derived growth factor (PDGF)- induced FMT of rat aortic adventitial fibroblasts. PLK4 inhibition (with centrinone-B or siRNA) diminished not only PDGF AA-induced proliferation/migration, but also smooth muscle a-actin and its transcription factor serum response factor’s activity. While PDGFR inhibition abrogated AA-stimulated PLK4 activation (phosphorylation) and mRNA/protein expression, inhibition of p38 downstream of PDGFR had a similar effect. Further, the transcription of PLK4 (and PDGFRa) was blocked by pan-inhibition of the bromo/extraterminal-domains chromatin-bookmark readers (BRD2, BRD3, BRD4), an effect herein determined via siRNAs as mainly mediated by BRD4. In vivo, periadventitial administration of centrinone-B reduced collagen content and thickness of the adventitia in a rat model of carotid artery injury. Thus, we identified a non-canonical role for PLK4 in FMT and its regulation by a BRD4/PDGFRa-dominated pathway. This study implicates a potential PLK4-targeted antifibrotic intervention. Keywords: PLK4, PDGF receptor-a, BRD4, fibroblast-to-myofibroblast transition, fibrosis”

- Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PLGA from PolySciTech used in development of new, large-scale nanoparticle manufacturing technique for drug-delivery applications

Wednesday, March 13, 2019, 4:16 PM ET

Nanoparticles are generated by carefully controlling the precipitation of polymers from a dissolved state to a solid state under reproducible conditions. Conventional methods to accomplish this, such as emulsion and dialysis, do not provide for highly uniform formation conditions. As such, these create a broad dispersity of nanoparticle sizes. Recent advances in microfluidics have enabled the generation of nanoparticles of uniform size however scalability remains a challenge. Recently, researchers at San Jose State University used PLGA (PolyVivo AP030) from PolySciTech (www.polyscitech.com) to develop a novel nanoparticle manufacturing technique based on a 3D-printed Multi-inlet vortex mixers with a specific herringbone design. This research holds promise to enable larger-scale manufacturing of nanoparticles. Read more: Bokare, Anuja, Ashley Takami, Jung Han Kim, Alexis Dong, Alan Chen, Ronald Valerio, Steven Gunn, and Folarin Erogbogbo. "Herringbone-Patterned 3D-Printed Devices as Alternatives to Microfluidics for Reproducible Production of Lipid Polymer Hybrid Nanoparticles." ACS Omega 4, no. 3 (2019): 4650-4657. https://pubs.acs.org/doi/abs/10.1021/acsomega.9b00128

“Major barriers to the implementation of nanotechnology include reproducible synthesis and scalability. Batch solution phase methods do not appear to have the potential to overcome these barriers. Microfluidic methods have been investigated as a means to enable controllable and reproducible synthesis; however, the most popular constituent of microfluidics, polydimethylsiloxane, is ill-suited for mass production. Multi-inlet vortex mixers (MIVMs) have been proposed as a method for scalable nanoparticle production; however, the control and reproducibility of the nanoparticle is wanting. Here, we investigate the ability to improve the control and reproducibility of nanoparticles produced by using 3D printed MIVMs with herringbone patterns in the flow channels. We compare three methods, viz., microfluidic, MIVM, and herringbone-patterned MIVM methods, for the synthesis of lipid–polymer hybrid nanoparticles (LPHNPs). The 3D printed herringbone-patterned MIVM method resulted in the smallest LPHNPs with the most uniform size distribution and shows more reproducible results as compared to the other two methods. To elucidate the mechanism underlying these results, concentration slices and vorticity streamlines of mixing chambers have been analyzed for 3D printed herringbone-patterned MIVM devices. The results bode well for LPHNPs, a formulation widely investigated for its improved therapeutic efficacy and biocompatibility. The herringbone-patterned device also has the potential to be broadly applied to many solution phase processes that take advantage of efficient mixing. The methods discussed here have broad implications for reproducible production of nanoparticles with constituents such as siRNA, proteins, quantum dots, and inorganic materials.”

- Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

- Check out PolySciTech’s new “Getting Started” guide to find initial product suggestions based on your application. You can see this here http://polyscitech.com/_start/

Recent Patent describes use of PolySciTech thermogels for treatment of ocular fungal infection

Tuesday, March 12, 2019, 1:44 PM ET

Fungal keratitis is a common and debilitating corneal disease in horses, with the reported incidence in North America of approximately 25% in 2013. This disease can be treated with antifungal agents such as voriconazole, however efficacy from conventional drops is low due to rapid clearance of the drug from the eye by tear formation and other processes. Recently, researchers at University of Auburn filed a patent on the use of PLGA-PEG-PLGA thermogels (Polyvivo AK012, AK024, AK019) from PolySciTech (www.polyscitech.com) for a thermogel to aid in the delivery of voriconazole as part of ocular treatment of fungal diseases. This research holds promise to prevent this potentially blinding disease. Read more: Duran, Sue H., Allison Stewart, William R. Ravis, Eva Abarca-piedrafita, Rosemary Cuming, and Mariono MORA PEREIRA. "Sustained-release voriconazole-containing thermogel and uses thereof." U.S. Patent Application 16/117,443, filed February 28, 2019. https://patents.google.com/patent/US20190060312A1/en

“Abstract: The present disclosure provides veterinary formulations comprising a therapeutically effective amount of a voriconazole and a polymer. The disclosure also provides methods, and kits for the treatment of disease, such as for treating a fungal infection in an animal utilizing the veterinary formulations. The invention relates to veterinary formulations comprising a therapeutically effective amount of a voriconazole and a polymer. First, a sustained-release veterinary formulation comprising voriconazole has great potential to improve comfort and ultimate outcome for animals suffering from keratomycosis, especially horses. Second, such a formulation can provide a treatment which would be available to all affected animals, regardless of budget, as it could be administered in the field. Third, the formulation, given via subconjunctival injection, would negate the need for frequent topical application of voriconazole to animals. This would result in minimizing stress in patients and improving compliance by decreasing the volume, frequency, and cost of medication required for treatment. Fourth, utilization of thermogel polymers (e.g., thermosensitive biodegradable hydrogels or ‘thermogels’) can advantageously be administered as a liquid, followed by conversion to a gel deposit upon reaching the appropriate temperature. As a result, the thermogel polymers can maintain a sustained release of drug at the site of administration in the animal, for example over weeks to months. The sustained release of voriconazole to an animal suffering from keratomycosis would increase the local bioavailability of the medication, decrease systemic side effects, and improve client compliance.”

- Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

- Check out PolySciTech’s new “Getting Started” guide to find initial product suggestions based on your application. You can see this here http://polyscitech.com/_start/

NEW: Product Application Starting Guide For PolySciTech Polymers

Thursday, March 7, 2019, 4:40 PM ET

In 2007 the PolyVivo product line started with eight simple block copolymers. Since that time, the catalog has grown to encompass over six-hundred products. From its inception, PolySciTech has put our customers in the driver’s seat of innovation. The majority of PolySciTech products are results from the multitude of customer requests we’ve received for new products over the years. The benefit from this is that the catalog is comprised of polymers which are in stock, rather than a listing of theoretical items which could be made by PolySciTech under request. The drawback is that the catalog listings are not organized along any particular pattern which makes navigating it challenging.

To assist customers with finding a polymer suggestion based on their application, we have created a ‘Getting Started Guide’ with helpful information and recommendations. This can be seen on our website here https://akinainc.com/polyscitech/_start/

PLGA-PEG-Mal from PolySciTech used in development of Saporin-loaded Nanoparticle for HER2+ Breast Cancer Therapy

Tuesday, March 5, 2019, 11:36 AM ET

Human epidermal growth factor receptor 2 (HER2) is a specific marker which is over-expressed on certain types of breast cancer and provides an opportunity for targeting nanoparticles towards the tumor cells. Similar to ricin toxin, saporin inactivates a cells ability to synthesize proteins which ultimately leads to the cells death. Unlike ricin, however, saporin has no inherent mechanism to actually enter a cell and as such presents no toxicity unless a specific mechanism is provided for it to enter the cell. Recently, researchers at Utrecht University (Netherlands) used PLGA-PEG-Mal (AI020) from PolySciTech (www.polyscitech.com) in research to create targeted nanoparticles which bind to HER2 marker on breast cancer and used photochemical delivery to introduce saporin into these cells leading to tumor death. This research holds promise to enable the treatment of highly metastatic and treatment-resistant forms of breast cancer. Read more: Martinez Jothar, Lucia, Nataliia Beztsinna, Cornelus F. van Nostrum, Wim E. Hennink, and Sabrina Oliveira. "Selective Cytotoxicity to HER2 Positive Breast Cancer Cells by Saporin-Loaded Nanobody-Targeted Polymeric Nanoparticles in Combination With Photochemical Internalization." Molecular Pharmaceutics. https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.8b01318

“In cancer treatment, polymeric nanoparticles (NPs) can serve as a vehicle for the delivery of cytotoxic proteins that have intracellular targets but that lack well-defined mechanisms for cellular internalization, such as saporin. In this work we have prepared PEGylated poly(lactic acid-co-glycolic acid-co-hydroxymethyl glycolic acid) (PLGHMGA) NPs for the selective delivery of saporin in the cytosol of HER2 positive cancer cells. This selective uptake was achieved by decorating the surface of the NPs with the 11A4 nanobody that is specific for the HER2 receptor. Confocal microscopy observations showed rapid and extensive uptake of the targeted NPs (11A4-NPs) by HER2 positive cells (SkBr3), but not by HER2 negative cells (MDA-MB-231). This selective uptake was blocked upon pre-incubation of the cells with an excess of nanobody. Non-targeted NPs (Cys-NPs) were not taken up by either type of cells. Importantly, a dose-dependent cytotoxic effect was only observed on SkBr3 cells when these were treated with saporin-loaded 11A4-NPs in combination with photochemical internalization (PCI), a technique that uses a photosensitizer and local light exposure to facilitate endosomal escape of entrapped nanocarriers and biomolecules. The combined use of saporin-loaded 11A4-NPs and PCI strongly inhibited cell proliferation and decreased cell viability through induction of apoptosis. Also the cytotoxic effect could be reduced by an excess of nanobody, reinforcing the selectivity of this system. These results suggest that the combination of the targeting nanobody on the NPs with PCI are effective means to achieve selective uptake and cytotoxicity of saporin-loaded NPs.”

- Interested in using polymers for drug-delivery, but looking for advice on which one to start with? Check out PolySciTech’s new “Getting Started” guide to narrow down some initial suggestions based on your application. You can see this here http://polyscitech.com/_start/

- Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PLGA from PolySciTech used in development of imaging technique for analysis of antibacterial coatings on orthopeadic implants.

Monday, March 4, 2019, 4:43 PM ET

Whenever an implant is surgically placed, there is always the potential for a bacterial infection to occur leading to an orthopedic implant-associated infection. One means to prevent this is to apply a biodegradable polymer coating which releases antibiotics from the implant to prevent the growth of bacteria in the area surrounding the implant. Recently, Researchers at Johns Hopkins University used PLGA (AP082, AP059) from PolySciTech (www.polyscitech.com) to provide for a model antibiotic-releasing implant coating to test an In vivo bioluminescence imaging technique for determining bacterial growth against. This research holds promise for improved development of bacterial-resistant implants to reduce the incidence of infection post-surgery. Read more: Miller, Robert J., John M. Thompson, Jesse Zheng, Mark C. Marchitto, Nathan K. Archer, Bret L. Pinsker, Roger V. Ortines et al. "In Vivo Bioluminescence Imaging in a Rabbit Model of Orthopaedic Implant-Associated Infection to Monitor Efficacy of an Antibiotic-Releasing Coating." JBJS 101, no. 4 (2019): e12. https://journals.lww.com/jbjsjournal/subjects/Oncology/Fulltext/2019/02200/In_Vivo_Bioluminescence_Imaging_in_a_Rabbit_Model.9.aspx

“Background: In vivo bioluminescence imaging (BLI) provides noninvasive monitoring of bacterial burden in animal models of orthopaedic implant-associated infection (OIAI). However, technical limitations have limited its use to mouse and rat models of OIAI. The goal of this study was to develop a larger, rabbit model of OIAI using in vivo BLI to evaluate the efficacy of an antibiotic-releasing implant coating. Methods: A nanofiber coating loaded with or without linezolid-rifampin was electrospun onto a surgical-grade locking peg. To model OIAI in rabbits, a medial parapatellar arthrotomy was performed to ream the femoral canal, and a bright bioluminescent methicillin-resistant Staphylococcus aureus (MRSA) strain was inoculated into the canal, followed by retrograde insertion of the coated implant flush with the articular surface. In vivo BLI signals were confirmed by ex vivo colony-forming units (CFUs) from tissue, bone, and implant specimens. Results: In this rabbit model of OIAI (n = 6 rabbits per group), implants coated without antibiotics were associated with significantly increased knee width and in vivo BLI signals compared with implants coated with linezolid-rifampin (p < 0.001 and p < 0.05, respectively). On day 7, the implants without antibiotics were associated with significantly increased CFUs from tissue (mean [and standard error of the mean], 1.4 × 108 ± 2.1 × 107 CFUs; p < 0.001), bone (6.9 × 106 ± 3.1 × 106 CFUs; p < 0.05), and implant (5.1 × 105 ± 2.2 × 105 CFUs; p < 0.05) specimens compared with implants with linezolid-rifampin, which demonstrated no detectable CFUs from any source. Conclusions: By combining a bright bioluminescent MRSA strain with modified techniques, in vivo BLI in a rabbit model of OIAI demonstrated the efficacy of an antibiotic-releasing coating. Clinical Relevance: The new capability of in vivo BLI for noninvasive monitoring of bacterial burden in larger-animal models of OIAI may have important preclinical relevance.”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

Folate-PEG, PEG-PLLA polymers from PolySciTech used in development of targeted nanoparticle photodynamic therapy of cancer

Thursday, February 21, 2019, 9:04 PM ET

Cancer therapy suffers from drawbacks due to the non-specific nature of chemotherapy as well as the invasive nature of surgical and radiological means of treatment. Targeted therapies which primarily affect the cancerous tissue without damaging healthy tissue hold promise to reduce the side-effects of cancer treatment. Recently, researchers at Wroclaw University (Poland) used mPEG-PLLA (AK004) and Folate-PEG-COOH (AE003) from PolySciTech (www.polyscitech.com) to create targeted nanoparticles for phototherapy. This research holds promise to improve treatment regiments for cancers. Read more: Lamch, Łukasz, Julita Kulbacka, Magda Dubińska-Magiera, Jolanta Saczko, and Kazimiera A. Wilk. "Folate-directed zinc (II) phthalocyanine loaded polymeric micelles engineered to generate reactive oxygen species for efficacious photodynamic therapy of cancers." Photodiagnosis and Photodynamic Therapy (2019). https://www.sciencedirect.com/science/article/pii/S1572100019300304

“Highlights: Folate functionalized block copolymers were used for zinc (II) phthalocyanine encapsulation. ZnPc-loaded micelles of FA-PEG-b-PLLA (DH<150 a="" abstract:="" accomplished="" accumulation="" addition="" after="" an="" analysis="" and="" anticancer="" application="" are="" atomic="" attached="" attractive="" b-plla="" b-poly="" be="" becoming="" biocompatible="" biomedical="" block="" br="" by="" can="" cancer="" carcinoma="" cell="" cells.="" cellular="" chain="" chemical="" colloid="" con="" conjunction="" copolymer="" copolymers="" cyto-="" cytoskeletal="" cytoskeleton="" delivered="" delivery.="" delivery="" demonstrated="" derivative="" diameter="" diblock="" distribution="" drug="" drugs="" dynamic="" e45="" effect.="" effective="" effects="" efficacy="" efficiently="" end="" enhanced="" entrapped="" ethylene="" evaluated="" f-actin="" fa-nanomicelles="" fda-approved="" folate-functionalized="" folate="" for="" force="" functionalized="" generation="" good="" imaging="" improve="" in="" index="" induced="" internalized="" intracellular="" is="" it="" its="" keywords:="" lactide="" ligand="" light="" lines.="" low="" me45="" measurements="" melanoma="" metastatic="" methoxypoly="" micellar="" micelles="" microscopy="" molecules="" morphology.="" mpeg-b-plla="" nanocarriers="" nanomedicine="" nm="" normal="" npc="" of="" option="" our="" ovarian="" oxide="" oxygen="" pdt="" peg="" performed="" permeability="" photocytotoxicity="" photodynamic="" photosensitizer="" phthalocyanine="" physical="" polydispersity="" polymeric="" potential="" procedures="" promising="" reaction.="" reaction="" reactive="" reduce="" reorganization.="" reorganization="" resistant="" resulting="" results="" retention="" rmed="" ros="" scattering="" second="" selective="" showed="" side="" since="" size="" skov-3="" smart="" species="" specific="" stability.="" stability="" studied="" studies="" study="" surface="" targeted="" that="" the="" their="" therapy="" therefore="" tissues.="" to="" transport="" undergoing="" used="" using="" via="" visualized="" was="" we="" were="" while="" with="" zinc="" znpc-smart="">
Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PLGA from PolySciTech described in patent application as part of manufacturing of PLGA/PEI particles for stem-cell delivery

Thursday, February 21, 2019, 9:03 PM ET

Stem-cells hold promise to treat a wide variety of diseases including cardiovascular disease. Recently, PLGA (AP089) from PolySciTech (www.polyscitech.com) was described as part of a process of making PLGA-PEI particles for stem-cell delivery in a recent patent from researchers at University of Utah. This research holds promise for treating cardiovascular diseases. Read more: Kim, Sung Wan, Kwang Suk Lim, and Young Sook Lee. "Plga/pei particles and methods of making and using the same." U.S. Patent Application 16/068,302, filed February 7, 2019. https://patents.google.com/patent/US20190038558A1/en

“Abstract: Poly(lactic-co-glycolic acid)/polyethylenimine (PLGA/PEI) particles and methods directed to the preparation of PLGA/PEI particles are provided. Methods of using PLGA/PEI particles for the proliferation of stem cells and/or delivery of stem cells are also provided. For example, methods of treating a subject having, or at risk of developing, a cardiovascular disorder can include administering a therapeutically effective amount of stem cell-loaded PLGA/PEI particles to the subject.”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

Website temporarily down 2-16-2019

Saturday, February 16, 2019, 4:05 PM ET

As of February 16, 2019, we are experiencing a loss of internet service to our location which is affecting our website (akinainc.com domain and affiliated sites). Thanks for your patience as we work to rectify this issue.

Biotech-Pharma-Cancer-Research (BPCR) Registration Now Open

Thursday, February 7, 2019, 4:29 PM ET

BPCR is a free, 1-day scientific Networking Conference which Akina, Inc. sponsors in the Purdue Research Park. This networking and scientific event allows for Purdue Research Park businesses, domestic research companies, and start-ups to meet with potential customers, investors and collaborators as well as, to get to know one another. There are open spots for Scientific Presentations (20 min) on research, Soapbox presentations on business opportunities (5 min), scientific poster session, as well as table-top displays for promotion and networking. see more and register at www.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 0.39284086227417 seconds)


Social Media

Facebook Twitter Google+ LinkedIn Google Blogger Hyperactive polymer ACS network
Privacy Policy