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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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

PLGA-PEG-NH2 from PolySciTech used in research on drug-delivery across the Blood-Brain-Barrier

Tuesday, June 18, 2019, 2:42 PM ET

In general uptake of medicinal molecules into the brain tissue from the blood-stream is very poor due to the blood-brain-barrier which generally prevents most molecules from getting into the brain. This naturally occurring phenomenon makes treatment of neural diseases very difficult. Recently, researchers at Universidade do Porto (Portugal) used PLGA-PEG-NH2 (AI058) from PolySciTech (www.polyscitech.com) used to create functional nanoparticles for controlling the crossing of the blood-brain-barrier. This research holds promise to improve efficacy of neural treatments for a variety of diseases. Read more: Maria João Bidarra Tavares Gomes “Modulation of drug efflux at the blood-brain barrier through targeted siRNA delivery via nanoparticles” PhD dissertation Universidade do Porto 2017. https://pdfs.semanticscholar.org/9a7e/057e12b64673536ad03b3560c4638941ee06.pdf

“Abstract (abbreviated): A BBB-targeted polymeric nanosystem was developed for delivery of siRNA against P-gp. Functionalized siRNA-loaded PLGA nanoparticles showed to be successful in silencing P-gp as a BBB efflux transporter and, consequently, in enhancing the blood-to-brain in vitro permeability of a P-gp substrate. Hence, drug efflux modulation at the BBB level was attained, bringing hope to CNS disorders treatments, since drugs could reach brain in higher and therapeutic concentrations. Additionally, being P-gp commonly over expressed at tumor cells, this polymeric system has the potential to be applied to cancer when properly functionalized to those cells.”

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-Rhodamine used in Research on Nanoparticle-based Cancer Therapy

Tuesday, June 18, 2019, 2:33 PM ET

One of the major drawbacks to conventional chemotherapy against cancer is that the drugs applied are often not specific to the cancer cells. Rather, they simply inhibit the growth of all cells (both tumor and healthy) which leads to severe side-effects of chemotherapy. One strategy to deal with this is to generate systems which direct the flow of the chemotherapeutic agents to the site of the tumor or into the cancer cells themselves. Recently, researchers at University of Minnesota used fluorescently-tagged PLGA-Rhodamine (AV011) from PolySciTech (www.polyscitech.com) to generate fluorescently traceable nanoparticles for MSC-mediated delivery to tumors. This research holds promise to improve the treatment of cancer. Read more: Layek, Buddhadev, Drishti Sehgal, Peter A. Argenta, Jayanth Panyam, and Swayam Prabha. "Nanoengineering of Mesenchymal Stem Cells via Surface Modification for Efficient Cancer Therapy." Advanced Therapeutics: 1900043. https://onlinelibrary.wiley.com/doi/pdf/10.1002/adtp.201900043

“Abstract: Mesenchymal stem cells (MSCs) can be used for tumor-specific delivery of small molecular weight anticancer drugs by using nanoparticle-encapsulated forms of the drugs. Current approaches to incorporate nanoparticles in MSCs rely on nonspecific endocytosis of nanoparticles or their conjugation to the cell surface via endogenous amines and thiols. These methods result in sub-optimal drug loading, which hinders the widespread application of MSCs as drug carriers. An advanced nanoengineering strategy is reported here that involves generation of MSCs expressing azide functional groups on their surface and conjugation of dibenzyl cyclooctyne-functionalized nanoparticles to the azide groups using copper-free click chemistry. This novel strategy significantly improves the payload capacity of MSCs (48 pg of paclitaxel (PTX) per cell) relative to that reported previously (<1 0.0001="" 0.05="" abraxane="" affecting="" agents="" allows="" an="" and="" anticancer="" as="" br="" carriers.="" cell="" chemotherapeutic="" compared="" conventional="" delivery="" drug="" efficacy="" encapsulated="" for="" free="" growth="" here="" improve="" improved="" in="" inhibit="" model.="" mscs="" nanoengineered="" nanoengineering="" nanoparticle="" native="" of="" or="" orthotopic="" ovarian="" p="" per="" pg="" phenotype.="" ptx="" reported="" significantly="" strategy="" summary="" survival="" the="" their="" to="" tumor="" using="" vivo="" without="">
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

Polyacrylamide from PolySciTech used in fundamental research on shear thickening/rheology

Wednesday, June 12, 2019, 3:26 PM ET

A fun experiment you can try at home is to mix 2 parts corn starch with 1 part water forming a colloidal suspension which flows easily under slight force but stiffens when exposed to a lot of force (shear thickening). This is a simple example of a non-Newtonian fluid (one in which the relationship between force and viscosity is not linear). Non-newtonian fluids of varying degrees of complexity have a wide array of uses both in industry and in medicine. Recently, researchers at University of Houston and Georgetown University used Polyacrylamide from PolySciTech (www.polyscitech.com) to test for the effects of colloidal attraction in non-Newtonian complex suspensions. This fundamental research holds promise for a wide variety of applications both industrial and biomedical. Read more: Park, Nayoung, Vikram Rathee, Daniel L. Blair, and Jacinta C. Conrad. "Contact Networks Enhance Shear Thickening in Attractive Colloid-Polymer Mixtures." Physical Review Letters 122, no. 22 (2019): 228003. https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.122.228003

“ABSTRACT: Increased shear thinning arising due to strong attractive interactions between colloidal particles is thought to obscure shear thickening. Here, we demonstrate how moderate attractions, induced by adding a nonadsorbing polymer, can instead enhance shear thickening. We measure the rheology of colloidal suspensions at a constant particle volume fraction of ϕ = 0.40 with dilute to weakly semidilute concentrations of three polyacrylamide depletants of different molecular weights. Suspensions containing large polymer exhibit increased shear thickening and positive first normal stress differences at high shear stress, and increased heterogeneous fluctuations in the boundary stress. These results are consistent with a friction-based model for shear thickening, suggesting that the presence of large, extended polymers induces the formation of near-spanning networks of interparticle contacts.”

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

PLCL from PolySciTech used in research on polymer degradation and mechanical properties

Tuesday, June 11, 2019, 4:42 PM ET

Polyesters degrade by hydrolysis of the ester bonds forming a random series of cuts along the chain which initially reduce the molecular weight and affect the mechanical properties before eventually degrading the entire piece away. This process is strongly affected by the environment around the polyester chain. Recently, researchers at Technical University of Liberec (Czech Republic) used PLCL from PolySciTech (www.polyscitech.com) to generate test samples. This research holds promise for a better understanding of degradation rate relationship to enzymes and other factors. Read more: Lisnenko, Maxim “ Impact of degradation on mechanical properties of nanofibrous polyester materials” Technical University of Liberec Thesis, 2019. https://dspace.tul.cz/bitstream/handle/15240/152429/Lisnenko_Maxim_BP_2018.pdf?sequence=1&isAllowed=y

“ABSTRACT The main aim of this work is a study the mechanical properties of polyester nanofibrous materials during degradation. The degradation of the materials was achieved by using enzymes that catalyse the decomposition of polyesters. The theoretical part describes, in brief, the production of nanofibrous layers by electrospinning. In addition to this, the part deals with the characteristic of the chemical-physical properties of the used materials such as PCL, PLCL and their Blend in particular, as well as a brief description of degradation types. The experimental part is focused on the description of the degradation of materials, which represents a simulation of the degradation process by using specific enzymes (Lipase and Proteinase K) in order to prepare the materials in different degrees of degradation and to measure their mechanical properties. Weight loss, molecular weight change, material morphology and crystallinity change were the determinants of degradation. A pull test was used as a determinant for mechanics. During the test tensile and deformation characteristics, such as tensile strength, ductility and the elastic modulus, are observed. Finally, the results of the work, which show that the degradation has a significant influence on the mechanical properties that deteriorate during the testing, are evaluated. KEY WORDS: nanofibers, degradation, polyesters, enzymatic degradation, mechanical properties”

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-PLA from PolySciTech used in development of nanoparticle-based brain-cancer therapy

Wednesday, June 5, 2019, 10:42 AM ET

One mechanism for treating cancer is to modify the genomic expression of the cancer cells reducing their potential to spread and cause pathological effects. Recently, Researchers at Arizona State University used mPEG-PLA (AK056) from PolySciTech (www.polyscitech.com) to create panobinostat loaded nanoparticles for cancer therapy. This research holds promise to treat medulloblastoma. Read more: Dharmaraj, Shruti. "Fabrication and Characterization of Panobinostat Loaded PLA-PEG Nanoparticles." PhD diss., Arizona State University, 2019. https://search.proquest.com/openview/f90b9cc74a56188a3c59b67784a746e2/1?pq-origsite=gscholar&cbl=18750&diss=y

“Medulloblastoma is the most common malignant pediatric brain cancer and is classified into four different subgroups based on genetic profiling: sonic hedgehog (SHH), WNT, Group 3 and 4. Changes in gene expression often alter the progression and development of cancers. One way to control gene expression is through the acetylation and deacetylation of histones. More specifically in medulloblastoma SHH and Group 3, there is an increased deacetylation, and histone deacetylase inhibitors (HDACi) can be used to target this change. Not only can HDACi target increases in deacetylation, they are also known to induce cell cycle arrest and apoptosis. The combination of these factors has made HDACi a promising cancer therapeutic. Panobinostat, a hydrophobic, small molecule HDACi was recently identified as a potent molecule of interest for the treatment of medulloblastoma. Furthermore, panobinostat has already been FDA approved for treatment in multiple myeloma and is being explored in clinical trials against various solid tumors. The laboratory is interested in developing strategies to encapsulate panobinostat within nanoparticles composed of the biodegradable and biocompatible polymer poly(lactic acid)-poly(ethylene glycol) (PLA-PEG). Nanoparticles are formed by single emulsion, a process in which hydrophobic drugs can be trapped within the hydrophobic nanoparticle core. The goal was to determine if the molecular weight of the hydrophobic portion of the polymer, PLA, has an impact on loading of panobinostat in PLA-PEG nanoparticles. Nanoparticles formulated with PLA of varying molecular weight were characterized for loading, size, zeta potential, controlled release, and in vivo tolerability. The results of this work demonstrate that panobinostat loaded nanoparticles are optimally formulated with a 20:5kDa PLA-PEG, enabling loading of ~3.2 % w/w panobinostat within nanoparticles possessing an average diameter of 102 nm and surface charge of -8.04 mV. Panobinostat was released from nanoparticles in a potentially biphasic fashion over 72 hours. Nanoparticles were well tolerated by intrathecal injection, although a cell culture assay suggesting reduced bioactivity of encapsulated drug warrants further study. These experiments demonstrate that the molecular weight of PLA influences loading of panobinostat into PLA-PEG nanoparticles and provide basic characterization of nanoparticle properties to enable future in vivo evaluation.”

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 thermogel from PolySciTech used in development of gene delivery system to reduce infections during pregnancy

Tuesday, May 28, 2019, 4:20 PM ET

According to the World Health Organization, an estimated 15 million babies are born preterm each year and the complications caused by premature birth are the leading cause of death among children under 5 years of age. One of the causes of premature birth, and other birth complications, is infection of the uterus during pregnancy with bacteria. Naturally occurring antimicrobial peptides in the cervical canal prevent these infections and encouraging the formation of these peptides could potentially protect pregnant women reducing the incidence of premature labor. Recently, researchers at University College London, King’s College London, Great Ormond Street Institute of Child Health (United Kingdom), and University of the Witwatersrand (South Africa) utilized PLGA-PEG-PLGA (PolyVivo AK012) from PolySciTech (www.polyscitech.com) to deliver a viral vector for gene transfer to the cervix in an animal model. They found this could be used to reduce infections during pregnancy. This research holds promise to reduce the incidence of premature birth. Read more: Suff, Natalie, Rajvinder Karda, Juan Antinao Diaz, Joanne Ng, Julien Baruteau, Dany Perocheau, Peter W. Taylor et al. "Cervical gene delivery of the antimicrobial peptide, Human β-defensin (HBD)-3, in a mouse model of ascending infection-related preterm birth." bioRxiv (2019): 643171. https://www.biorxiv.org/content/10.1101/643171v1.abstract

“Approximately 40% of preterm births are preceded by microbial invasion of the intrauterine space: ascent from the vagina is the most common pathway. Within the cervical canal, antimicrobial peptides and proteins (AMPs) help to constitute a barrier which prevents ascending infection. We investigated whether expression of the AMP, human β-defensin-3 (HBD3), in the cervical mucosa prevented bacterial ascent from the vagina into the uterine cavity of pregnant mice. An adeno-associated virus vector containing both the HBD3 gene and GFP transgene (AAV8 HBD3.GFP) or control (AAV8 GFP), was administered intravaginally into E13.5 pregnant mice. Ascending infection was induced at E16.5 using bioluminescent E.coli (E.coli K1 A192PP-lux2). Bioluminescence imaging showed bacterial ascent into the uterine cavity, cellular events that led to premature delivery and a reduction in pups born alive, compared with uninfected controls. In addition, a significant reduction in uterine bioluminescence in the AAV8 HBD3.GFP-treated mice was observed 24 hours post-E.coli infection, compared to AAV8 GFP treated mice, signifying reduced bacterial ascent in AAV8 HBD3.GFP-treated mice. There was also an increase in the number of living pups in AAV HBD3.GFP-treated mice. We propose that HBD3 may be considered a possible candidate for augmenting cervical innate immunity to prevent ascending infection-related preterm birth.”

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

Memorial Day Closure

Friday, May 24, 2019, 3:36 PM ET

Akina, Inc. will be closed May 27, 2019 for Memorial Day. Orders placed at that time will be processed the following day.

PLA-PEG-Maleimide from PolySciTech used in development of long-lasting vaccines against infections

Tuesday, May 14, 2019, 2:08 PM ET

The human immune system can be visualized as an angry guard dog on a long chain. The dog has enough power and bite to destroy just about anything within its area but, in order to be effective, it must be trained carefully as to who is and is not allowed within its sector (i.e. “self” versus “non-self” designations). In this metaphor, vaccine technology would be equivalent to showing the guard dog a picture of a known thief and instructing it to bite said thief on sight. Of course, humans cannot ‘speak’ to the immune system, so unraveling the biochemical language by which the immune system can be ‘trained’ to attack deadly pathogens is critical to preventing epidemics. Recently, researchers at DILIsym Services Inc., Mylan Pharmaceuticals Inc., University of Nebraska, Eppley Institute for Research in Cancer and Allied Diseases, San Diego State University, and Creighton University used mal-PEG-PLA (AI050) from PolySciTech (www.polyscitech.com) to create modified nanoparticles which were decorated with an immunogenic-peptide on the outside to act as an adjuvant in vaccine technology. This research holds promise for the development of more effective vaccines against a wide range of diseases. Read more: Tallapaka, Shailendra B., Bala VK Karuturi, Pravin Yeapuri, Stephen M. Curran, Yogesh A. Sonawane, Joy A. Phillips, D. David Smith, Sam D. Sanderson, and Joseph A. Vetro. "Surface conjugation of EP67 to biodegradable nanoparticles increases the generation of long-lived mucosal and systemic memory T-cells by encapsulated protein vaccine after respiratory immunization and subsequent T-cell-mediated protection against respiratory infection." International Journal of Pharmaceutics (2019). https://www.sciencedirect.com/science/article/pii/S0378517319303667

“Abstract: Encapsulation of protein vaccines in biodegradable nanoparticles (NP) increases T-cell expansion after mucosal immunization but requires incorporating a suitable immunostimulant to increase long-lived memory T-cells. EP67 is a clinically viable, host-derived peptide agonist of the C5a receptor that selectively activates antigen presenting cells over neutrophils. We previously found that encapsulating EP67-conjugated CTL peptide vaccines in NP increases long-lived memory subsets of CTL after respiratory immunization. Thus, we hypothesized that alternatively conjugating EP67 to the NP surface can increase long-lived mucosal and systemic memory T-cells generated by encapsulated protein vaccines. We found that respiratory immunization of naïve female C57BL/6 mice with LPS-free ovalbumin (OVA) encapsulated in PLGA 50:50 NP (∼380 nm diameter) surface-conjugated with ∼0.1 wt% EP67 through 2 kDa PEG linkers (i.) increased T-cell expansion and long-lived memory subsets of OVA323-339-specific CD4+ and OVA257-264-specific CD8a+ T-cells in the lungs (CD44HI/CD127/KLRG1) and spleen (CD44HI/CD127/KLRG1/CD62L) and (ii.) decreased peak CFU of OVA-expressing L. monocytogenes (LM-OVA) in the lungs, liver, and spleen after respiratory challenge vs. encapsulation in unmodified NP. Thus, conjugating EP67 to the NP surface is one approach to increase the generation of long-lived mucosal and systemic memory T-cells by encapsulated protein vaccines after respiratory immunization. Keywords: mucosal vaccine vaccine delivery nanoparticle targeted vaccines dendritic cell targeting CD88 host-derived immunostimulant complement-derived immunostimulant”

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 from Akina used in development of Ultrasound-Triggered Neural delivery Nanoparticles

Monday, May 13, 2019, 10:14 AM ET

Neuroactive agents which are designed to have a specific effect on the brain suffer from several drawbacks. One of these is the non-specific nature of their action in which certain neural pathways are either blocked or activated regardless of location. Recently, researchers at Stanford University used mPEG-PLGA (AK090) from PolySciTech (www.polyscitech.com) to create nanoparticles that can be controlled by external ultra-sound signals. This research holds promise to enable specific delivery of compounds to discrete locations of the brain in a more controlled manner to treat a variety of disease states. Read more: Wang, Jeffrey B., Muna Aryal, Qian Zhong, Daivik B. Vyas, and Raag D. Airan. "Noninvasive Ultrasonic Drug Uncaging Maps Whole-Brain Functional Networks." Neuron 100, no. 3 (2018): 728-738. https://www.sciencedirect.com/science/article/pii/S0896627318309504

“Highlights: Ultrasound-sensitive nanoparticles enable localized drug delivery to the brain. Ultrasonic drug uncaging allows noninvasive and precise control of brain activity. Drug effects are limited to the ultrasound focus and by the kinetics of the drug. Uncaging and neuroimaging together causatively maps whole-brain functional networks. Being able to noninvasively modulate brain activity, where and when an experimenter desires, with an immediate path toward human translation is a long-standing goal for neuroscience. To enable robust perturbation of brain activity while leveraging the ability of focused ultrasound to deliver energy to any point of the brain noninvasively, we have developed biocompatible and clinically translatable nanoparticles that allow ultrasound-induced uncaging of neuromodulatory drugs. Utilizing the anesthetic propofol, together with electrophysiological and imaging assays, we show that the neuromodulatory effect of ultrasonic drug uncaging is limited spatially and temporally by the size of the ultrasound focus, the sonication timing, and the pharmacokinetics of the uncaged drug. Moreover, we see secondary effects in brain regions anatomically distinct from and functionally connected to the sonicated region, indicating that ultrasonic drug uncaging could noninvasively map the changes in functional network connectivity associated with pharmacologic action at a particular brain target. Keywords: focused ultrasound neuromodulation functional imaging functional connectivity nanotechnology 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

Akinalytics Publication Highlights PLGA Analysis Methods and Capabilities for ‘Sameness’ Determination

Thursday, May 9, 2019, 1:47 PM ET

In addition to providing for polymer products through the PolySciTech division, Akina, Inc. also provides for analysis of materials through the Akinalytics group (http://www.akinalytics.com/). A series of collaborations with the Food and Drug Administration Office of Generic Drugs have generated a great deal of data and methodology expertise in the realm of understanding the characterization of PLGA. This developed further understanding of a commonly used polymer can be applied both for formulation development as well as for establishing ‘sameness’ between a reference listed product and a proposed generic. Read more here: Kinam Park, Sarah Skidmore, Justin Hadar, John Garner, Haesun Park, Andrew Otte, Bong Kwan Soh, Gwangheum Yoon, Dijia Yu, Yeonhee Yun, Byung Kook Lee, Xiaohui Jiang (Jeff), Yan Wang. “Injectable, long-acting PLGA formulations: Analyzing PLGA and understanding microparticle formation.” Journal of Controlled Release (2019). https://www.sciencedirect.com/science/article/pii/S0168365919302512

“Abstract: Injectable, long-acting depot formulations based on poly(lactide-co-glycolide) (PLGA) have been used clinically since 1989. Despite 30 years of development, however, there are only 19 different drugs in PLGA formulations approved by the U.S. Food and Drug Administration (FDA). The difficulty in developing depot formulations stems in large part from the lack of a clear molecular understanding of PLGA polymers and a mechanistic understanding of PLGA microparticles formation. The difficulty is readily apparent by the absence of approved PLGA-based generic products, limiting access to affordable medicines to all patients. PLGA has been traditionally characterized by its molecular weight, lactide:glycolide (L:G) ratio, and end group. Characterization of non-linear PLGA, such as star-shaped glucose-PLGA, has been difficult due to the shortcomings in analytical methods typically used for PLGA. In addition, separation of a mixture of different PLGAs has not been previously identified, especially when only their L:G ratios are different while the molecular weights are the same. New analytical methods were developed to determine the branch number of star-shaped PLGAs, and to separate PLGAs based on L:G ratios regardless of the molecular weight. A deeper understanding of complex PLGA formulations can be achieved with these new characterization methods. Such methods are important for further development of not only PLGA depot formulations with controllable drug release kinetics, but also generic formulations of current brand-name products. Keywords PLGA Long-acting depot L:G ratio Glucose-PLGA Star-shape Q1/Q2”

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

Akinalytics Publication Details PLGA-Branching Analysis Development for PLGA-Glucose/Sandostatin

Thursday, May 9, 2019, 1:45 PM ET

In addition to linear chains, polymers can be synthesized into a variety of branched configurations including star, comb, and semi-branched polymers. For several types of polymers, there are a variety of methods to measure and analyze the branching. However, no such method has existed for PLGA until just now. As part of a collaboration effort with the Food and Drug Administration Office of Generic Drugs, Akina has developed methods around GPC-4D which enable characterization of branching in branched PLGAs including PLGA-Glucose used in Sandostatin. This and other evaluation techniques are available through the Akinalytics group (http://www.akinalytics.com/). Read more: Hadar, Justin, Sarah Skidmore, John Garner, Haesun Park, Kinam Park, Yan Wang, Bin Qin, and Xiaohui Jiang. “Characterization of branched poly (lactide-co-glycolide) polymers used in injectable, long-acting formulations.” Journal of Controlled Release (2019). https://www.sciencedirect.com/science/article/pii/S0168365919302421

“Abstract: Poly(lactide-co-glycolide) (PLGA) has been used in many injectable, long-acting depot formulations. Despite frequent use of PLGA, however, its characterization has been limited to measuring its molecular weight, lactide:glycolide (L:G) ratio, and end-group. These conventional methods are not adequate for characterization of unique PLGA polymers, such as branched PLGA. Glucose-initiated PLGA (Glu-PLGA) has been used in Sandostatin® LAR Depot (octreotide acetate for injectable suspension) approved by the U.S. Food and Drug Administration (FDA) in 1998. Glu-PLGA is a branched (also known as star-shaped) polymer and determining its properties has been challenging. It is necessary to develop methods that can determine and characterize the branching parameters of Glu-PLGA. Such characterization is important not only for the quality control of formulations, but also for developing generic parenteral formulations that are required to have the same excipients in the same amount (qualitative/quantitative (Q1/Q2) sameness) as their Reference Listed Drug (RLD). In this study, an analytical technique was developed and validated using a series of branched-PLGA standards, and it was used to determine the branching parameters of Glu-PLGA extracted from Sandostatin LAR, as well as Glu-PLGAs obtained from three different manufacturers. The analytical technique was based on gel-permeation-chromatography with quadruple detection systems (GPC-4D). GPC-4D enabled characterization of Glu-PLGA in its concentration, absolute molecular weight, hydrodynamic radius and intrinsic viscosity. The plot of the branch units per molecule as a function of molar mass provides a unique profile of each branched PLGA. The Mark-Houwink plots were also used to distinguish different Glu-PLGAs. These ensemble identification methods indicate that the branch units of Glu-PLGAs extracted from Sandostatin LAR range from 2 (i.e., linear) at the lower end of the molecular weight to <4 br="" branched="" depot="" for="" glu-plga.="" keywords:="" long-acting="" majority="" of="" plga="" q1="" sameness="" sandostatin="" star-shape="" the="">
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 from PolySciTech used in development of peptide-loaded nanoparticles to treat bone-disease

Tuesday, May 7, 2019, 4:11 PM ET

Normal human bone is in a constant state of growth and remodeling by a balance between osteoblasts (which grow new bone) and osteoclasts (which remove old bone). Several bone-diseases (osteoporosis and others) involve an imbalance in these processes where bone is resorbed in an unhealthy manner. Recently, researchers at University of Maryland used mPEG-PLGA (AK010) from PolySciTech (www.polyscitech.com) to create nanoparticles loaded with a newly developed peptide-based medicine that reduces bone resorption process. This research holds promise to provide for improved therapies against a variety of diseases which attack bone. Read more: Sunipa Majumdar, Aniket S. Wadajkar, Hanan Aljohani, Mark A. Reynolds, Anthony J. Kim, and Meenakshi Chellaiah “Engineering of L-Plastin Peptide-Loaded Biodegradable Nanoparticles for Sustained Delivery and Suppression of Osteoclast Function In Vitro” International Journal of Cell Biology Volume 2019, Article ID 6943986, 13 pages https://doi.org/10.1155/2019/6943986

“Abstract: We have recently demonstrated that a small molecular weight amino-terminal peptide of L-plastin (10 amino acids; “MARGSVSDEE”) suppressed the phosphorylation of endogenous L-plastin. Therefore, the formation of nascent sealing zones (NSZs) and bone resorption are reduced. The aim of this study was to develop a biodegradable and biocompatible PLGA nanocarrier that could be loaded with the L-plastin peptide of interest and determine the efficacy in vitro in osteoclast cultures. L-plastin MARGSVSDEE (P1) and scrambled control (P3) peptide-loaded PLGA-PEG nanoparticles (NP1 and NP3, respectively) were synthesized by double emulsion technique. The biological effect of nanoparticles on osteoclasts was evaluated by immunoprecipitation, immunoblotting, rhodamine-phalloidin staining of actin filaments, and pit forming assays. Physical characterization of well-dispersed NP1 and NP3 demonstrated ~130-150 nm size, < 0.07 polydispersity index, ~-3 mV ζ-potential, and a sustained release of the peptide for three weeks. Biological characterization in osteoclast cultures demonstrated the following: NP1 significantly reduced (a) endogenous L-plastin phosphorylation; (b) formation of NSZs and sealing rings; (c) resorption. However, the assembly of podosomes which are critical for cell adhesion was not affected. L-plastin peptide-loaded PLGA-PEG nanocarriers have promising potential for the treatment of diseases associated with bone loss. Future studies will use this sustained release of peptide strategy to systematically suppress osteoclast bone resorption activity in vivo in mouse models demonstrating bone loss.”

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

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.40584683418274 seconds)


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