John Garner's Technical Blog
John GarnerJohn Garner, Manager

What's New and on the Manager's Mind

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


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PLGA from PolySciTech used in optimization of nanoparticle encapsulation of chemotherapeutic agent.

Tuesday, November 12, 2019, 11:27 AM ET

The single-emulsion technique is a widely used methodology to form nanoparticles when the drug to be loaded is hydrophobic enough to be directly dissolved into the organic solvent along with the polymer. The exact size and loading efficiency of these particles varies based on the manufacturing parameters and these can be optimized to provide for the highest quality nanoparticles. Recently, researchers at University of Houston used PLGA (AP041) from PolySciTech (www.polyscitech.com) and single-emulsion based techniques to optimize the nanoparticle encapsulation method for a chemotherapy drug. This research holds promise for improved therapy against cancer. Read more: Holley, Claire K., Bridgett Sinquefield, and Sheereen Majd. "Optimization of the Single Emulsion Method for Encapsulation of a Cancer Drug in Nanoparticles." In 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), pp. 1078-1081. IEEE, 2019. https://ieeexplore.ieee.org/abstract/document/8857458/

“Abstract: The goal of this study is to apply and optimize the single emulsion technique for encapsulation of an anti-tumor drug, Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), in nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA), as a step towards targeted delivery of this drug. We previously showed that the nanoprecipitation technique can effectively produce PLGA NPs carrying this drug. Here, we aim to examine the single emulsion technique as an alternative for the preparation of these NPs and to compare the resultant NPs to those from nanoprecipitation. We fabricated NPs with variations in (i) injection rate, (ii) the amount of surfactant poly (vinyl alcohol) (PVA) in aqueous phase, and (iii) concentration of PLGA in the organic phase. These NPs were characterized for size, surface potential, and encapsulation efficiency. The results revealed that increasing the injection rate (from manual addition to 90 mL/hr via syringe pump) greatly reduced the size of NPs (by 48%) and decreasing the PVA concentration in the aqueous phase (from 5 to 1% w/v) further reduced the NP size (by 32%) to 329 nm. All tested NP formulations had negative surface potential, suggesting good colloidal stability for these NPs. Focusing on the optimal injection rate and PVA percentage, we found that reducing the concentration of PLGA, from 100 to 1 mg/mL, significantly reduced the NP size to 136 nm, which is close to the optimal range for cancer therapeutic delivery. NPs produced by this method had a high encapsulation efficiency of 77% for Dp44mT and reducing the PLGA concentration slightly lowered this value to 74%. Overall, these NPs were comparable to those produced by nanoprecipitation and can thus, serve as an effective alternative for delivery of Dp44mT to cancer cells.”

mPEG-PLA and PLA-PEG-COOH from PolySciTech used in development of prostate cancer therapy

Tuesday, November 12, 2019, 11:26 AM ET

Ensuring appropriate delivery of drug molecules to the location of action is critical for their efficacy. Prostate cancer is one of the most common types of cancer in men and can be aggressive and spread. This type of cancer can be targeted by a specific antigen. Recently, researchers at Mashhad University of Medical Sciences (Iran) used mPEG-PLA (AK054) and PLA-PEG-COOH (AI030) from PolySciTech (www.polyscitech.com) to create galbanic acid/docetaxel loaded nanoparticles decorated with a targeting molecule for prostate cancer treatment. This research holds promise to provide for improved therapies against this common type of cancer. Read more: Afsharzadeh, Maryam, Maryam Hashemi, Maryam Babaei, Khalil Abnous, and Mohammad Ramezani. "PEG‐PLA nanoparticles decorated with small‐molecule PSMA ligand for targeted delivery of galbanic acid and docetaxel to prostate cancer cells." Journal of cellular physiology (2019). https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.29339

“Abstract: Prostate cancer (PCa) is one of the most prevalent non‐drug delivery system cutaneous malignancies. Undoubtedly, introducing novel treatment options to achieve higher therapeutic index will be worthwhile. In this study, we report for the first time, a novel targeted self‐assembled based on PEG‐PLA nanoparticles (PEG‐PLA NPs) containing galbanic acid (GBA) and docetaxel, which was targeted using ((S)‐2‐(3‐((S)‐5‐amino‐1‐carboxypentyl) ureido) pentanedioic acid (ACUPA), a small molecule inhibitor targeting prostate‐specific membrane antigen (PSMA), in prostate cancer cell line. The prepared NPs were characterized by different analytical methods. The MTT assay was used to compare the anti‐proliferation of drugs‐loaded PEG‐PLA NPs and ACUPA‐PEG‐PLA against LNCaP (PSMA+) and PC3 (PSMA−) cells. PEG‐PLA NPs with an average size of 130–140 nm had an enhanced release of GBA and docetaxel at pH 5.5 compared with pH 7.5. Spectrofluorometric analysis suggested that ACUPA‐modified PEG‐PLA could effectively enhance the drug uptake in PSMA+ prostate cancer cells. Cytotoxicity studies showed that the targeted NPs loaded with different concentrations of GBA and fixed concentration of docetaxel (4 nM) have shown higher toxicity (IC50 30 ± 3 µM) than both free GBA (80 ± 4.5 µM) and nontargeted NPs (IC50 40 ± 4.6 µM) in LNCaP cells. Collectively, these findings suggest that ACUPA‐conjugated PEG‐PLA nanosystem containing GBA and docetaxel is a viable delivery carrier for various cancer‐targeting PSMA that suffer from short circulation half‐life and limited therapeutic efficacy.”

mPEG-PLA from PolySciTech used in development of continuous nanoparticle generation system for large-scale nanoparticle production

Friday, November 1, 2019, 3:09 PM ET

Nanoparticles are generated by the carefully controlled solvent extraction of a polymer solution under emulsifying conditions which causes the polymer to self-form into small spheres (nanoparticles). There are many ways to generally accomplish this, however most have to be done in batch mode and are limited in scale. Recently, researchers at ETH Zurich (Switzerland) used mPEG-PLA (AK056) from PolySciTech (www.polyscitech.com) for generation of nanoparticles using a novel coaxial mixing system which can rapidly generate large quantities of particles. This research holds promise to enable large-scale production of nanoparticles. Read more: Bovone, Giovanni, Elia A. Guzzi, and Mark W. Tibbitt. "Flow‐based reactor design for the continuous production of polymeric nanoparticles." AIChE Journal (2019). https://aiche.onlinelibrary.wiley.com/doi/abs/10.1002/aic.16840

“Abstract: Polymeric nanoparticles (NPs) are versatile and effective drug delivery systems (DDS) that can be produced via nanoprecipitation of block copolymers. Yet, translation into clinical products has been limited. Thus, methods for NP production that enable rapid formulation screening and continuous production are needed. Toward this end, we engineered a coaxial jet mixer (CJM) for controlled and continuous nanoprecipitation in flow. The CJM enabled continuous assembly of poly(ethylene glycol)‐block‐polylactide NPs with various co‐solvents and was compared to batch nanoprecipitation. Other fabricated microfluidic devices were suitable for small scale formulation screening but more limited in scalable and continuous processes. In contrast, the CJM was tolerant to all water‐miscible solvents tested, enabled formulation screening, and scalable production of NPs and DDS. In total, the CJM provides a complementary approach to the process engineering of polymeric NP formation that can be used broadly for formulation screening and production.”

PLGA from PolySciTech used in study on nanoparticle biodistribution based on particle size.

Friday, November 1, 2019, 3:09 PM ET

When nanoparticles are injected into a body several competing forces come into play which drive their motion. There are many features which affect this localization one of which is relative size of the particles. Recently, researchers at Yale University used PLGA (AP041) from PolySciTech (www.polyscitech.com) for generation of nanoparticles. These were then used to track their biodistribution across living systems to determine which organs/tissues they primarily transported too. This research holds promise to enable future developments of tissue-targeted nanoparticles based on particle size. Read more: Mandl, Hanna K., Elias Quijano, Hee Won Suh, Emily Sparago, Sebastian Oeck, Molly Grun, Peter M. Glazer, and W. Mark Saltzman. "Optimizing Biodegradable Nanoparticle Size for Tissue-Specific Delivery." Journal of Controlled Release (2019). https://www.sciencedirect.com/science/article/pii/S0168365919305589

“Abstract: Nanoparticles (NPs) are promising vehicles for drug delivery because of their potential to target specific tissues [1]. Although it is known that NP size plays a critical role in determining their biological activity, there are few quantitative studies of the role of NP size in determining biodistribution after systemic administration. Here, we engineered fluorescent, biodegradable poly(lactic-co-glycolic acid) (PLGA) NPs in a range of sizes (120–440 nm) utilizing a microfluidic platform and used these NPs to determine the effect of diameter on bulk tissue and cellular distribution after systemic administration. We demonstrate that small NPs (∼120 nm) exhibit enhanced uptake in bulk lung and bone marrow, while larger NPs are sequestered in the liver and spleen. We also show that small NPs (∼120 nm) access specific alveolar cell populations and hematopoietic stem and progenitor cells more readily than larger NPs. Our results suggest that size of PLGA NPs can be used to tune delivery to certain tissues and cell populations in vivo.”

Polylactide from PolySciTech used in analysis of temperature and humidity effects on polymer mechanical behavior.

Friday, October 25, 2019, 3:12 PM ET

Polymers can be visualized as long chains. The chains can be in a random jumble (amorphous) or neatly lined up and stacked tightly together (crystalline) or various combinations in between. The degree of organization of the polymers plays a dramatic role in the mechanical stiffness and strength of the materials made from the polymer. A classic example for this is polyvinylchloride which is both used for generation of garden-hoses (flexible) and credit-cards (stiff). Based on the processing and additives used, PVC can either be extremely flexible or extremely stiff. Recently, researchers at University of Wisconsin−Madison used PLA (AP164) to perform mechanical analysis under different conditions for determining humidity and temperature effects on polymer behavior. This research holds promise in furthering understanding about polymer behavior in solid state. Read more: Ricci, Josh, Trevor Bennin, Enran Xing, and M. D. Ediger. "Linear Stress Relaxation and Probe Reorientation: Comparison of the Segmental Dynamics of Two Glassy Polymers during Physical Aging." Macromolecules (2019). https://pubs.acs.org/doi/abs/10.1021/acs.macromol.9b01625

“Segmental dynamics of glassy poly(methyl methacrylate) (PMMA) and poly(lactic acid) (PLA) have been measured over 8 h of aging via both optical probe reorientation and mechanical stress relaxation experiments performed in the linear response regime, in a temperature range between 6 and 30 K below the glass transition temperature (Tg). A clear power law relationship between relaxation times and aging times is observed in all experiments. For both PLA and PMMA glasses, the probe reorientation times are strongly correlated with stress relaxation times over the observed range of aging times and aging temperatures, with the two relaxation times related by a power law with an exponent of ∼1. Comparisons of these data sets with previously published work indicate that the relationship between the two relaxation times is not influenced by secondary relaxation processes, low levels of crosslinking, or the presence of a plasticizer. These results support the view that the probe reorientation technique is a good reporter of segmental dynamics in the glassy state.”

PLGA-PEG-NHS from PolySciTech used in development of Cetuximab-decorated nanoparticles for cancer therapy

Monday, October 21, 2019, 4:38 PM ET

Cetuximab is an antibody which attaches to the overexpressed EGFR on the surfaces of certain types of cancer. In addition to serving as a form of chemotherapy in and of itself, this molecule can also be used for targeting purposes. Recently, researchers at Queen's University Belfast (UK) and State University of New York used PLGA-PEG-NHS (AI064) from PolySciTech (www.polyscitech.com) to create cetuximab-covered nanoparticles for delivery of camptothecin to tumor cells. This research holds promise for improved therapy against cancer. Read more: McDaid, William J., Michelle K. Greene, Michael C. Johnston, Ellen Pollheimer, Peter Smyth, Kirsty McLaughlin, Sandra Van Schaeybroeck, Robert M. Straubinger, Daniel B. Longley, and Christopher J. Scott. "Repurposing of Cetuximab in antibody-directed chemotherapy-loaded nanoparticles in EGFR therapy-resistant pancreatic tumours." Nanoscale (2019). https://pubs.rsc.org/en/content/articlehtml/2019/nr/c9nr07257h

“Abstract: The anti-Epidermal Growth Factor Receptor (EGFR) antibody Cetuximab (CTX) has demonstrated limited anti-cancer efficacy in cells overexpressing EGFR due to activating mutations in RAS in solid tumours, such as pancreatic cancer. The utilisation of antibodies as targeting components of antibody–drug conjugates, such as trastuzumab emtansine (Kadcyla), demonstrates that antibodies may be repurposed to direct therapeutic agents to antibody-resistant cancers. Here we investigated the use of CTX as a targeting agent for camptothecin (CPT)-loaded polymeric nanoparticles (NPs) directed against KRAS mutant CTX-resistant cancer cells. CPT was encapsulated within poly(lactic-co-glycolic acid) (PLGA) NPs using the solvent evaporation method. CTX conjugation improved NP binding and delivery of CPT to CTX-resistant cancer cell lines. CTX successfully targeted CPT-loaded NPs to mutant KRAS PANC-1 tumours in vivo and reduced tumour growth. This study highlights that CTX can be repurposed as a targeting agent against CTX-resistant cancers and that antibody repositioning may be applicable to other antibodies restricted by resistance.”

PLGA from PolySciTech used in development of novel nanoparticle manufacturing method

Monday, October 14, 2019, 4:20 PM ET

There are many ways to manufacture nanoparticles and each method brings specific pros and cons in terms of its application to the generation of new nanoparticles. Notably, microfluidic techniques provide for much higher degrees of control for nanoparticle fabrication than previously possible by conventional methods. Recently, researchers at Assiut University (Egypt) and American University of Sharjah (UAE) used PLGA (AP154) from PolySciTech (www.polyscitech.com) used in development of nanoparticles generated by a novel microfluidic-based method. This research holds promise for the improved development of nanoparticles in the future. Read more: Abualsayed, Alsaeed, Sara Abouelmagd, and Mohamed Abdelgawad. "Miniaturized Preparation of polymeric nanoparticles using droplet manipulation on open surfaces." Micro & Nano Letters (2019). https://digital-library.theiet.org/content/journals/10.1049/mnl.2019.0421?crawler=true

“A digital microfluidics platform for the preparation of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) was developed. Droplets of PLGA in dimethylformamide were merged with droplets of deionised water by electrical actuation on a digital microfluidics device to form PLGA NPs through nanoprecipitation. The developed platform is automated and allows for the preparation of polymeric NPs with small size and high uniformity. Using the platform, the authors were able to prepare monodisperse PLGA NPs as small as 115 nm with a polydispersity index (PDI) of 0.14 which can be challenging with conventional preparation techniques on the macroscale. Size of the prepared NPs can be tuned through proper choice of the volume ratio between the two merged droplets which controls the induced internal convection flow after merging. Concentration of PLGA in the dimethylformamide droplet also had an effect on the size and polydispersity of the formed NPs. These results prove the potential use of digital microfluidics for testing combinatorial synthesis of different polymeric NPs for various applications. This approach allows robust and automated screening of NP preparations using only few microlitres of the reagents used, thus conserving precious and costly NP components and loaded therapeutic agents.”

PLGA from PolySciTech used in development of Lycopene encapsulation system

Monday, October 14, 2019, 4:19 PM ET

Lycopene is a naturally occurring carotenoid which is found in red colored fruits and vegetables (notably tomatoes). This compound has strong antioxidant effects however it is delicate and easily damaged as well as poorly water soluble. Encapsulating lycopene in a biodegradable carrier may potentially aid in delivery of the molecule. Recently, researchers at Alabama A&M University used PLGA (AP041) from PolySciTech (www.polyscitech.com) to create nanoparticles and tested these for their size and zeta potential properties. This research holds promise to improve the potential therapeutic application for lycopene. Read more: Alam, Mohammad Anwar Ul, and Lamin S. Kassama. "Comparative Study of Lycopene Encapsulation Efficiency in Polycapprolactone Vs Poly Lactic Co-glycolic Acid." In 2019 ASABE Annual International Meeting, p. 1. American Society of Agricultural and Biological Engineers, 2019. https://elibrary.asabe.org/abstract.asp?aid=50671

“Lycopene contributes to the red-colored pigmentation of fruits and vegetables, and it is a fat-soluble carotenoid with antioxidant properties. Epidemiological studies have shown the significant health benefits associated to the consumption of lycopene rich foods, because of the anti-cancer properties. Degradative losses of lycopene during processing is a grave concern, hence encapsulation provides a remedy. The objective of this study is to evaluate the encapsulation efficiency of two biodegradable polymers (PLGA and PCL) as for controlled release of lycopene in the gastrointestinal (GI) system. The nanoparticles (NP) were synthesized by emulsion evaporation method and physicochemical properties was determined using a Dynamic Light Scattering spectroscopy. The results show the hydrodynamic diameter of the lycopene NP synthesized in PCL (200 mg) and 3500 mg surfactant and sonicated for 15 min was 79.23±0.85 nm (Lowest). PLGA (500 mg) and 500 mg surfactant with 15 min sonication was observed to have the lowest NP diameter (108.2±2.66 nm) among the others. Significant difference result found in PDI value (0.12±0.07) when PCL of 200mg dissolve in 3500 mg of surfactant. On the other hands the zeta potential values were much smaller in case of PCL NP ranged between -1.3±0.046 and -4.21±0.08 mV compared to the PLGA NP -72.36±2.17 to 107.66±3.15 mV in all experiments. Thus, NP synthesized with PCL and surfactant provide a smaller sized nano-solution than PLGA and surfactant. As the degradation rate for PCL is lower than PLGA so PCL can be considered as a potential biodegradable polymer than PLGA to encapsulate lycopene. Keywords: PLGA, PCL, NP, nano-encapsulation, lycopene, encapsulation efficiency”

PLGA-PEG-PLGA thermogel used in design of vaccine adjuvant as part of development of male contraceptive

Tuesday, October 8, 2019, 4:43 PM ET

In vaccines, an adjuvant is another substance or compound included to boost the immune response against the antigen. Thermogelling PLGA-PEG-PLGA can be used for this as it provides for extended release of the antigen as well as a slight pro-inflammatory response. Recently, there has been a great deal of research in the development of a male contraceptive that can be provided as a dosed medication (rather than a simple physical barrier such as a condom). This research has yielded Gonadotropin-releasing hormone as a target which can be blocked and subsequently prevent the downstream development of sperm. Recently, researchers at Auburn University and Charles River Laboratories used PLGA-PEG-PLGA (AK097) from PolySciTech (www.polyscitech.com) to create a thermogel injection for male contraceptive and tested this in cats. This research holds promise to provide for improved reproductive control. Read more: Johnson, Aime K., Rebecca L. Jones, Carol J. Kraneburg, Anna M. Cochran, Alexandre M. Samoylov, James C. Wright, Cynthia Hutchinson et al. "Phage constructs targeting gonadotropin-releasing hormone for fertility control: evaluation in cats." Journal of Feline Medicine and Surgery (2019): 1098612X19875831. https://journals.sagepub.com/doi/abs/10.1177/1098612X19875831

“Abstract: Objectives: Phage–gonadotropin-releasing hormone (GnRH) constructs with potential contraceptive properties were generated in our previous study via selection from a phage display library using neutralizing GnRH antibodies as selection targets. In mice, these constructs invoked the production of antibodies against GnRH and suppressed serum testosterone. The goal of this study was to evaluate this vaccine against GnRH for its potential to suppress reproductive characteristics in cats. Methods: Sexually mature male cats were injected with a phage–GnRH vaccine using the following treatment groups: (1) single phage–GnRH vaccine with adjuvant; (2) phage–GnRH vaccine without adjuvant and half-dose booster 1 month later; or (3) phage–GnRH vaccine with adjuvant and two half-dose boosters with adjuvant 3 and 6 months later. Anti-GnRH antibodies and serum testosterone, testicular volume and sperm characteristics were evaluated monthly for 7–9 months. Results: All cats developed anti-GnRH antibodies following immunization. Serum antibody titers increased significantly after booster immunizations. In group 3, serum testosterone was suppressed 8 months after primary immunization. Total testicular volume decreased in group 1 by 24–42% and in group 3 by 15–36% at 7 months after immunization, indicating potential gonadal atrophy. Vacuolation of epididymides was observed histologically. Although all cats produced sperm at the conclusion of the study, normal morphology was decreased as much as 38%. Phage alone produced no local or systemic reactions. Immunization of phage with AdjuVac produced unacceptable injection site reactions. Conclusions and relevance: Our phage-based vaccine against GnRH demonstrated a potential for fertility impairment in cats. Future research is required to optimize vaccine regimens and identify animal age groups most responsive to the vaccine. If permanent contraception (highly desirable in feral and shelter cats) cannot be achieved, the vaccine has a potential use in zoo animals or pets where multiple administrations are more practical and/or reversible infertility is desirable. Keywords Fertility control, filamentous phage, gonadotropin-releasing hormone, GnRH”

Akina, Inc. Employment Opportunity: Laboratory Technician

Monday, September 30, 2019, 9:54 AM ET

Laboratory Technician
Akina, Inc. is looking for an Laboratory Technician to assist in research and development of biomedical products and services including, but not limited to, Restiex(R) expanders, contracted research analysis, and development of the PolySciTech line of research products. The position primarily involves bench-chemistry and will involve chemical and polymer synthesis as well as advanced analytical techniques. Work done on-site at West Lafayette, Indiana facility. Pay is competitive starting from $25/hr.
Either a bachelors or associates degree in Chemistry, Biology, Biomedical Research, or related scientific field.
Full-time work-week availability (Mon-Fri, 8AM-5PM) to be on-site at laboratory in West Lafayette, IN (not eligible for remote work).
Must have passed undergraduate-level organic chemistry for this position.
Previous experience preferred, but not necessary.
Position not eligible for work visa sponsorship.
If you are interested please send your resume to jg@akinainc.com

(Original posting here http://akinainc.com/employment.php)

PLGA-PEG polymers from PolySciTech used in development of collagen-binding nanoparticles to prevent post-surgical adhesion

Tuesday, September 24, 2019, 3:27 PM ET

After a surgery, it is common for adhesions to form as the healing tissues will sometime heal to one another forming connections which are not meant to be there. These surgical adhesions create painful issues which can lead to side effects and complications. Recently, researchers at University of North Carolina at Chapel Hill, Duke University, and Jilin University (China) used mPEG-PLGA (AK029), Mal-PEG-PLGA (AI110), and PLGA-PEG-COOH (AI034) from PolySciTech (www.polyscitech.com) to create nanoparticles to prevent post-surgical adhesion. This research holds promise to prevent a common surgical complication. Read more: Mi, Yu, Feifei Yang, Cameron Bloomquist, Youli Xia, Bo Sun, Yanfei Qi, Kyle Wagner, Stephanie A. Montgomery, Tian Zhang, and Andrew Z. Wang. "Biologically Targeted Photo‐Crosslinkable Nanopatch to Prevent Postsurgical Peritoneal Adhesion." Advanced Science (2019): 1900809. https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.201900809

“Abstract: Peritoneal adhesion occurs in a majority of patients following abdominal surgery and can result in significant side effects and complications. Current strategies to minimize adhesions involve the use of nontargeted anatomical barriers that are either inefficient in protecting injured areas or lacking the adequate residence time to prevent adhesions. Herein, the development of a biologically targeted photo-crosslinkable nanopatch (pCNP) is reported that can prevent postsurgical adhesion. It is demonstrated that pCNP can form a compact protective barrier over surfaces with exposed collagen IV. Using a rat parietal peritoneal excision adhesion model, it is showed that pCNP is highly effective and safe in preventing postsurgical adhesions. This work presents a novel approach to preventing peritoneal adhesion with nanomaterials.”

PLGA-Rhodamine from PolySciTech used in development of nanoparticle for Tuberculosis treatment

Tuesday, September 24, 2019, 3:26 PM ET

Tuberculosis is a fatal disease which can be treated by specific antibiotic drugs. Due to poor bioavailability and localization, these drugs are typically administered at high doses which can lead to liver damage. Recently, researchers at Université Paris-Sud (France) and Universidade Federal de Ouro Preto (Brazil) used PLGA-Rhodamine (AV011) from PolySciTech (www.polyscitech.com) to generate fluorescently traceable nanoparticles for targeted TB treatment. This research holds promise to provide for improved therapy against tuberculosis with less liver damage. Read more: Carneiro, Simone Pinto, Laurence Moine, Barbara Tessier, Valerie Nicolas, Orlando DH dos Santos, and Elias Fattal. "Pyrazinoic acid-Poly (malic acid) biodegradable nanoconjugate for efficient intracellular delivery." Precision Nanomedicine 2, no. 3 (2019): 303-317. https://precisionnanomedicine.com/api/v1/articles/9660-pyrazinoic-acid-poly-malic-acid-biodegradable-nanoconjugate-for-efficient-intracellular-delivery.pdf

“Abstract: Tuberculosis is an infectious disease affecting mostly lungs, that is still considered a health global problem as it causes millions of deaths worldwide. Current treatment is effective but associated with severe adverse effects due to the high doses of each anti-tuberculosis drug daily administrated by oral therapy. For the first time, a pyrazinoic acid (PA) biodegradable nanoconjugate was synthesized and developed for pulmonary administration in an attempt to reduce the administered doses by achieving a high drug payload and controlled release at the target site. The conjugate was synthesized by coupling pyrazinoic acid on carboxylic groups of poly(malic acid), which is a biodegradable and biocompatible polymer, and posteriorly self-assembled into nanoconjugates. Characterization confirmed the formation of nanometric, spherical and negatively charged pyrazinoic acid nanoconjugate (NC-PA). NC-PA was stable for 60 days at 4 and 37°C and able to deliver PA in a sustained release manner over time. On macrophages, they exhibited no cell toxicity for a wide range of concentrations (from 1 to 100 μg/mL), demonstrating the safety of NC-PA. In addition, the nanoconjugate was efficiently taken up by RAW 264.7 cells over 6 hours reaching a maximum value after 3 hours of incubation. In conclusion, innovative nanoconjugates are a promising alternative to deliver drugs directly to the lungs and contributing to improving tuberculosis therapy.”

PLGA from PolySciTech used in development of small-scale melt-processing system.

Wednesday, September 18, 2019, 10:28 AM ET

Melt processing is the process by which a polymer is heated to a fluid state and then forced into a mold or through a cavity to adapt into a specific shape. This includes many common techniques for generating products from polymers or plastic such as blow-molding, extrusion, injection molding, and vacuum forming. The vast majority of melt-processing equipment is designed to process kilo’s to metric tons of polymers and are designated for manufacturing. This creates a condition which is prohibitive to researchers looking to perform melt-processing on polymers at small scale for testing and development. Recently, researchers at University of California used PLGA (AP041) from PolySciTech (www.polyscitech.com) in their development of a small-scale melt-processing system. This research holds promise to enable research and development of materials made by this processing method. Read more: Wirth, David M., and Jonathan K. Pokorski. "Design and fabrication of a low-cost pilot-scale melt-processing system." Polymer (2019): 121802. https://www.sciencedirect.com/science/article/pii/S0032386119308080

“Highlights: Schematics for facile assembly of a lab scale mini-injection molding system. Less than $500 in raw materials, melt processes polymers at up to 250 °C with 100 MPa pressure. Ideal for small samples 50–500 mg total mass with low dead volume. Non-newtonian modeling of shear rate inside melt processing system. Abstract: Melt processing of polymeric materials is a ubiquitous technique for forming, shaping, refining and homogenizing polymers and polymer composites. Melt-processing techniques are the primary manufacturing method of consumer and industrial thermoplastic parts, especially when using commodity polymers with high-throughput production. Melt-processing, however, is underutilized in academic laboratories when developing high value-added materials due to the capital expense of the equipment and relatively large-scale required to carry out such processing. These concerns make pilot-scale melt-processing challenging, particularly for the development of new polymers or polymer composites where materials can only be generated in small-scale at reasonable costs. The current study designs and evaluates a bench-top, sub-milliliter volume extrusion and injection-molding device, which sources parts from current 3D printer technology at minimal expense. The plans presented will open this convenient technique to academic research laboratories interested in pilot-scale experiments. A systematic approach to melt processing of PLA, PLGA, and PCL polymer composites is demonstrated. Characterization of the dispersion of pharmaceuticals, small molecules and nanoparticles in melt processed polymers is presented as a demonstration of potential utility. Keywords: Melt processing Composites Injection molding Polymer engineering”

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

BPCR Registration Deadlines Approaching

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

2019 CRS Meeting Update: Posters and Presentations available

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

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

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.45428395271301 seconds)


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