Monday, March 1, 2021

PLGAs from PolySciTech used in development of periodontal-simulating test chamber for drug release assays


PLGA microparticles are routinely used for delivery of long-acting injectable drugs. For these formulations, the drug is encapsulated in the biodegradable PLGA and elutes out slowly due to drug diffusion and polymer degradation. A rather critical question is at what rate the drug elutes out and this depends on the formulation parameters and polymer type used. In order to test this, however, a system must be designed which replicates the important components of the human body and allows for the drug elution to be measured using HPLC or other analytical techniques. Arestin is a unique formulation in that it is designed to go into the periodontal pocket (gumline) around teeth and slowly release antibacterial agents for localized activity. Due to the location of this formulation (as opposed to typical intra-muscular injection sites in the shoulder or buttocks used for conventional LAR formulations) it has a rather unique local environment in the gumline which is difficult to replicate. Recently, researchers at University of Pittsburgh, Magee-Women’s Research Institute, Qrono Inc, and Food and Drug Administration used multiple PLGAs (AP125, AP037, AP081, AP030, AP150) purchased from PolySciTech (www.polyscitech.com) to develop a variety of PLGA-minocycline formulations and test these out on a novel flow-release chamber used to represent the periodontal pocket release. This research holds promise to improve analytical techniques applied for testing long-acting injectable formulations. Read more: Patel, Sravan Kumar, Ashlee C. Greene, Stuti M. Desai, Sam Rothstein, Iman Taj Basha, James Scott MacPherson, Yan Wang et al. "Biorelevant and screening dissolution methods for minocycline hydrochloride microspheres intended for periodontal administration." International Journal of Pharmaceutics 596 (2021): 120261. https://www.sciencedirect.com/science/article/pii/S037851732100065X

“Abstract: Currently, there is no compendial-level method to assess dissolution of particulate systems administered in the periodontal pocket. This work seeks to develop dissolution methods for extended release poly(lactic-co-glycolic acid) (PLGA) microspheres applied in the periodontal pocket. Arestin®, PLGA microspheres containing minocycline hydrochloride (MIN), is indicated for reduction of pocket depth in adult periodontitis. Utilizing Arestin® as a model product, two dissolution methods were developed: a dialysis set-up using USP apparatus 4 and a novel apparatus fabricated to simulate in vivo environment of the periodontal pocket. In the biorelevant method, the microspheres were dispersed in 250 μL of simulated gingival crevicular fluid (sGCF) which was enclosed in a custom-made dialysis enclosure. sGCF was continuously delivered to the device at a biorelevant flow rate and was collected daily for drug content analysis using UPLC. Both methods could discriminate release characteristics of a panel of MIN-loaded PLGA microspheres that differed in composition and process conditions. A mechanistic model was developed, which satisfactorily explained the release profiles observed using both dissolution methods. The developed methods may have the potential to be used as routine quality control tools to ensure batch-to-batch consistency and to support evaluation of bioequivalence for periodontal microspheres. Keywords: Dissolution PLGA Minocycline Biorelevant Microspheres Periodontal Modeling”

Wednesday, February 24, 2021

PLGA-PEG-Biotin from PolySciTech used in development of multifunctional Janus nanoparticles

 

In ancient Roman mythology, Janus is the god of doors and gates. He is depicted as having two faces because he is both looking outward and inward at the same time. Having a dual nature is a property which would be desirable for nanoparticles as this will enable the ability for more complicated functions. Recently, researchers at University of California San Francisco used PLGA-PEG-Biotin (AI167) and PLGA (AP061) to create long, tubular nanoparticles with different functionalities based on orientation. This research holds promise to allow more complicated nanotechnology operations by having higher control over the shape and geospatial considerations of nanoparticles. Read more: Finbloom, Joel A., Yiqi Cao, and Tejal A. Desai. "Bioinspired Polymeric High Aspect Ratio Particles with Asymmetric Janus Functionalities." Advanced NanoBiomed Research: 2000057. https://onlinelibrary.wiley.com/doi/abs/10.1002/anbr.202000057

“Abstract: Polymeric particles with intricate morphologies and properties have been developed based on bioinspired designs for applications in regenerative medicine, tissue engineering, and drug delivery. However, the fabrication of particles with asymmetric functionalities remains a challenge. Janus polymeric particles are an emerging class of material with asymmetric functionalities; however, they are predominantly spherical in morphology, made from non‐biocompatible materials, and made using specialized fabrication techniques. We therefore set out to fabricate nonspherical Janus particles inspired by high aspect ratio filamentous bacteriophage using polycaprolactone polymers and standard methods. Janus high aspect ratio particles (J‐HARPs) were fabricated with a nanotemplating technique to create branching morphologies selectively at one edge of the particle. J‐HARPs were fabricated with maleimide handles and modified with biomolecules such as proteins and biotin. Regioselective modification was observed at the tips of J‐HARPs, likely owing to the increased surface area of the branching regions. Biotinylated J‐HARPs demonstrated cancer cell biotin receptor targeting, as well as directional crosslinking with spherical particles via biotin‐streptavidin interactions. Lastly, maleimide J‐HARPs were functionalized during templating to contain amines exclusively at the branching regions and were dual‐labeled orthogonally, demonstrating spatially separated bioconjugation. Thus, J‐HARPs represent a new class of bioinspired Janus material with excellent regional control over biofunctionalization.”

Monday, February 22, 2021

PLA-PEG-PLA diacrylate from PolySciTech Used in testing of crosslinked rituximab-loaded nanoparticles for treatment of non-Hodgkin’s lymphoma in novel mouse model

 


Replicating the human body conditions in another animal is not a trivial task however necessary for creating therapies against complex diseases such as cancer which can not be replicated using cell-cultures or other benchtop techniques. Recently, researchers at University of California Los Angeles and University of Alabama used PLA-PEG-PLA-diacrylate (AI102) from PolySciTech (www.polyscitech.com) to form crosslinked particles loaded with Rituximab as a cancer therapy and tested these against a novel mouse model. This research holds promise to improve both therapies and testing of those therapies for treatment of cancer. Read more: Wen, Jing, Lan Wang, Jie Ren, Emiko Kranz, Shilin Chen, Di Wu, Toshio Kanazawa, Irvin Chen, Yunfeng Lu, and Masakazu Kamata. "Nanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model." Journal for ImmunoTherapy of Cancer 9, no. 2 (2021): e001524. https://jitc.bmj.com/content/9/2/e001524.abstract

“Abstract: Background Despite the numerous applications of monoclonal antibodies (mAbs) in cancer therapeutics, animal models available to test the therapeutic efficacy of new mAbs are limited. NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice are one of the most highly immunodeficient strains and are universally used as a model for testing cancer-targeting mAbs. However, this strain lacks several factors necessary to fully support antibody-mediated effector functions—including antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity (CDC)—due to the absence of immune cells as well as a mutation in the Hc gene, which is needed for a functional complement system. Methods: We have developed a humanized mouse model using a novel NSG strain, NOD.Cg−Hc1Prkdcscid Il2rgtm1Wjl/SzJ (NSG−Hc1), which contains the corrected mutation in the Hc gene to support CDC in addition to other mechanisms endowed by humanization. With this model, we reevaluated the anticancer efficacies of nanoencapsulated rituximab after xenograft of the human Burkitt lymphoma cell line 2F7-BR44. Results: As expected, xenografted humanized NSG−Hc1 mice supported superior lymphoma clearance of native rituximab compared with the parental NSG strain. Nanoencapsulated rituximab with CXCL13 conjugation as a targeting ligand for lymphomas further enhanced antilymphoma activity in NSG−Hc1 mice and, more importantly, mediated antilymphoma cellular responses. Conclusions: These results indicate that NSG−Hc1 mice can serve as a feasible model for both studying antitumor treatment using cancer targeting as well as understanding induction mechanisms of antitumor cellular immune response.”

Wednesday, February 17, 2021

PLGA from PolySciTech used in development of HER2-targeted doxycycline-based nanoparticle therapy for breast cancer.

 

With the exclusion of very specific types of breast cancer, such as triple-negative breast cancer lines, most breast cancers present human epidermal growth factor receptor 2 (HER2) marker on their surface. The use of compounds which selectively attach to this marker (such as Trastuzumab (TZB)) allows for delivery of materials specifically to the tumor cells to treat the cancer. Recently, researchers at Universidad de Guadalajara, Universidad de Sonora (Mexico), Universidad Tecnológica Metropolitana, Universidad de Chile, and Advanced Center for Chronic Diseases (Chile) used PLGA (AP081) from PolySciTech (www.polyscitech.com) to create doxycycline-loaded nanoparticles coated with HER2 targeting ligand as a treatment for breast cancer. This research holds promise to improve therapies against this potentially fatal disease in the future. Read more: Escareño, Noé, Natalia Hassan, Marcelo J. Kogan, Josué Juárez, Antonio Topete, and Adrián Daneri-Navarro. "Microfluidics-Assisted Conjugation of Chitosan-Coated Polymeric Nanoparticles with Antibodies: Significance in Drug Release, Uptake, and Cytotoxicity in Breast Cancer Cells." Journal of Colloid and Interface Science (2021). https://www.sciencedirect.com/science/article/pii/S0021979721001648

“Nanoparticle-based drug delivery systems, in combination with high-affinity disease-specific targeting ligands, provide a sophisticated landscape in cancer theranostics. Due to their high diversity and specificity to target cells, antibodies are extensively used to provide bioactivity to a plethora of nanoparticulate systems. However, controlled and reproducible assembly of nanoparticles (NPs) with these targeting ligands remains a challenge. In this context, determinants such as ligand density and orientation, play a significant role in antibody bioactivity; nevertheless, these factors are complicated to control in traditional bulk labeling methods. Here, we propose a microfluidic-assisted methodology using a PDMS (polydimethylsiloxane) Y-shaped microreactor for the covalent conjugation of Trastuzumab (TZB), a recombinant antibody targeting HER2 (human epidermal growth factor receptor 2) to doxorubicin-loaded PLGA/Chitosan NPs (PLGA/DOX/Ch NPs) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysulfosuccinimide (sNHS) mediated bioconjugation reactions. Our labeling approach led to smaller and less disperse nanoparticle-antibody conjugates providing differential performance when compared to bulk-labeled NPs in terms of drug release kinetics (fitted and analyzed with DDSolver), cell uptake/labeling, and cytotoxic activity on HER2+ breast cancer cells in vitro. By controlling NP-antibody interactions in a laminar regime, we managed to optimize NP labeling with antibodies resulting in ordered coronas with optimal orientation and density for bioactivity, providing a cheap and reproducible, one-step method for labeling NPs with globular targeting moieties. Keywords: Microfluidics polymeric nanoparticles PLGA nanoparticles chitosan antibody antibody-nanoparticle conjugate”

Tuesday, February 16, 2021

Weather Closure 2-16-2021

 Due to extreme winter weather, Akina Inc. is closed for operations 2-16-2021. Orders placed at this time will be filled the next available business day.

Monday, February 15, 2021

Weather Advisory 2/15/2021

Weather Advisory 2/15/2021: Due to severe winter weather, Akina Inc. will be operating at limited capacity and will be unable to ship orders placed today and tomorrow. Orders placed during this time will be sent out at next available business day.

PLGA from PolySciTech Used in development of antibacterial surfaces for surgical implants to prevent infection

 


A common problem with surgical interventions is the potential for bacterial infections to grow and spread particularly along the surfaces of implanted materials. In addition to conventional asceptic surgical practices the use of surfaces which release antibiotics and have antimicrobial properties can prevent such infections. Recently, researchers at Università di Perugia (Italy) used PLGA (AP020) from PolySciTech (www.polyscitech.com) along with zirconium phosphate to produce polymeric composites which released antibacterial and other compounds to prevent infection. This research holds promise to reduce surgery-related infections. Read more: Pica, Monica, Nicla Messere, Tommaso Felicetti, Stefano Sabatini, Donatella Pietrella, and Morena Nocchetti. "Biofunctionalization of Poly (lactide-co-glycolic acid) Using Potent NorA Efflux Pump Inhibitors Immobilized on Nanometric Alpha-Zirconium Phosphate to Reduce Biofilm Formation." Materials 14, no. 3 (2021): 670. https://www.mdpi.com/982146

“Abstract: Polymeric composites, where bioactive species are immobilized on inorganic nanostructured matrix, have received considerable attention as surfaces able to reduce bacterial adherence, colonization, and biofilm formation in implanted medical devices. In this work, potent in-house S. aureus NorA efflux pump inhibitors (EPIs), belonging to the 2-phenylquinoline class, were immobilized on nanometric alpha-zirconium phosphate (ZrP) taking into advantage of acid-base or intercalation reactions. The ZrP/EPI were used as filler of poly(lactide-co-glycolic acid) (PLGA) to obtain film composites with a homogeneous distribution of the ZrP/EPI fillers. As reference, PLGA films loaded with ZrP intercalated with thioridazine (TZ), that is recognized as both a NorA and biofilm inhibitor, and with the antibiotic ciprofloxacin (CPX) were prepared. Composite films were characterized by X-ray diffraction, scanning electron microscopy, and thermogravimetric analysis. The ability of the composite films, containing ZrP/EPI, to inhibit biofilm formation was tested on Staphylococcus aureus ATCC 29213 and Staphylococcus epidermidis ATCC 12228, and it was compared with that of the composite loaded with ZrP/TZ. Finally, the antibacterial activity of CPX intercalated in ZrP was evaluated when used in combination with ZrP/EPI in the PLGA films. Keywords: zirconium phosphate; PLGA; Efflux pump inhibitors; biofilm inhibition; composites”