Wednesday, January 20, 2021

Mal-PEG-PLGA/PEG-PLGA from PolySciTech Used in Development of immune-modulating treatment for multiple sclerosis

 

Several diseases in the human body are driven by a pathological over-reaction of the human immune system. Examples of this include crohn’s disease, and multiple schlerosis. In the case of multiple sclerosis the immune system attacks the nerve coverings leading to severe, chronic disease. Recently, researchers at Drexel University and University of Pennsylvania used Mal-PEG-PLGA (AI020) and mPEG-PLGA (AK037) from PolySciTech (www.polyscitech.com) division of Akina, Inc. to create antigen decorated nanoparticles to prevent the immune system from attacking the nerve tissue. This research holds promise to provide for development of immune tolerance as a treatment for autoimmune diseases. Read more: Li, Peter Y., Frank Bearoff, Pu Zhu, Zhiyuan Fan, Yucheng Zhu, Mingyue Fan, Laura Cort, Taku Kambayashi, Elizabeth P. Blankenhorn, and Hao Cheng. "PEGylation enables subcutaneously administered nanoparticles to induce antigen-specific immune tolerance." Journal of Controlled Release. https://www.sciencedirect.com/science/article/pii/S0168365921000225

“Abstract: The development of nanomaterials to induce antigen-specific immune tolerance has shown promise for treating autoimmune diseases. While PEGylation has been widely used to reduce host immune responses to nanomaterials, its tolerogenic potential has not been reported. Here, we report for the first time that a subcutaneous injection of PEGylated poly(lactide-co-glycolide) (PLGA) nanoparticles containing auto-antigen peptide MOG35–55 without any tolerogenic drugs is sufficient to dramatically ameliorate symptoms after disease onset in an antigen-specific manner in a mouse model of multiple sclerosis. Neither free MOG35–55 nor particles without PEG exhibit this efficacy. Interestingly, mechanistic studies indicate that PEGylation of nanoparticles does not reduce dendritic cell activation through direct nanoparticle-cell interactions. Instead, PEGylated nanoparticles induce lower complement activation, neutrophil recruitment, and co-stimulatory molecule expression on dendritic cells around the injection sites than non-PEGylated PLGA nanoparticles, creating a more tolerogenic microenvironment in vivo. We further demonstrate that the locally recruited dendritic cells traffic to lymphoid organs to induce T cell tolerance. These results highlight the critical role of surface properties of nanomaterials in inducing immune tolerance via subcutaneous administration. Keywords: Immunotherapy Local immune modulation Immune cell recruitment Anergy Experimental autoimmune encephalomyelitis Biomaterials”

Friday, January 15, 2021

PLGA from PolySciTech used in development of antibiotic releasing surgical clip

 


Whenever an incision is made in a patient as part of surgery there is a potential for infection to spread as bacteria grow in the wound. Typical surgical-practice measures (sterilization of instruments, scrubbing-in, wearing of surgical masks, etc.) minimize the potential for bacteria to invade the space, however post-surgical infections still occur as it is nearly impossible to completely eliminate all bacteria from a given area. Recently, researchers at Drexel University and Exponent Inc. used PLGA (AP075) from PolySciTech (www.polyscitech.com) to create a surgical clip that releases vancomycin (antibiotic) to prevent post-surgical infections. This research holds promise to improve surgical outcomes. Read more: Schachtner, J., R. Nathan, M. Rajaghatta, B. Shah, A. Suarez, N. Hickok, and S. Kurtz. "3D-Printed Bioresorbable Antibiotic Spacer Clip for the Prevention of Spinal Surgical Site Infection." Antimicrobial Combination Devices: 65-74. https://www.astm.org/DIGITAL_LIBRARY/STP/PAGES/STP163020190143.htm

“Abstract: Surgical site infections (SSIs) are serious complications of spinal fusion surgery and are often difficult to eradicate due to the formation of bacterial biofilms on the implanted hardware. SSIs affect 1% to 8.5% of patients after spinal surgery, with a 2.1% SSI rate after lumbar spinal fusion surgery. The objective of this study is to aid in the prevention of spinal SSIs by designing an adjunct to spinal hardware that contains a reservoir for the bolus release and extended release of prophylactic antibiotics in order to reduce the consequences of these painful, costly, and life-threatening infections. A clip was designed with a dual wall that includes an inner structural layer of polylactic acid (PLA) to contain vancomycin and an outer composite layer of poly(lactic-co-glycolic acid) (PLGA) and vancomycin. The inner well is ruptured by ultrasound to allow the bolus vancomycin release. An extended release of vancomycin then continues as the material of the clip degrades. The clip was printed using a dual-head three-dimensional (3D) printer to enable two separate types of filament—a coextruded PLGA/vancomycin composite for the outer wall and a medical-grade PLA for structural support. The PLGA/vancomycin material was evaluated for its efficacy against Staphylococcus aureus and its ability to prevent biofilm formation. This material was tested against three control groups, and the processed antibiotic was shown to be as effective as the unprocessed vancomycin solution. To understand the extended-release profile of the material, tests were conducted to study the zones of inhibition of the antibiotic eluted from the clip in PBS over a period of 10 days. This study presents an opportunity for the development of antimicrobial devices in 3D printing and the possibility of different antibiotic and polymer composite materials. Keywords: 3D printing, fused filament fabrication, bioresorbable polymer, surgical site infection, PLGA, Staphylococcus aureus, vancomycin, antimicrobial”

Thursday, January 14, 2021

PEG-PLA from PolySciTech used to investigate the impact of chemotherapy delivery during pregnancy

 


Treatment of breast cancer during pregnancy can be problematic as care must be taken to ensure the therapy applied doesn’t damage either mother or child. Unfortunately, many of the conventional chemotherapeutic agents used to prevent the growth of cancer can also negatively impact the growing fetus. Recently, researchers at University of Texas used mPEG-PLA (AK069) from PolySciTech (www.polyscitech.com) to investigate the effects of nanoparticle formulations on placental uptake in pregnant women. This research highlights the need for diligence and care with treating breast cancer in pregnant women without causing damage to other areas. Read more: Ali, Shariq, Norah A. Albekairi, Sanaalarab Al-Enazy, Mansi Shah, Svetlana Patrikeeva, Tatiana N. Nanovskaya, Mahmoud S. Ahmed, and Erik Rytting. "Formulation effects on paclitaxel transfer and uptake in the human placenta." Nanomedicine: Nanotechnology, Biology and Medicine: 102354. https://www.sciencedirect.com/science/article/pii/S1549963420302082

“Highlights: Nanoparticle formulations of drugs alter their permeability across human placenta. Encapsulation of paclitaxel in micelles prevents placental efflux by P-glycoprotein. Reduced efflux of paclitaxel leads to increased placental accumulation. Abstract: Diagnosis and treatment of breast cancer in pregnancy can result in morbidity and mortality for the mother and fetus. Many new paclitaxel nanoformulations commercially available worldwide for breast cancer treatment are being adopted due to favorable dosing regimens and side effect profiles, but their transplacental transport and resultant fetal exposure remains unknown. Here, we examine three formulations: Taxol (paclitaxel dissolved in Kolliphor EL and ethanol); Abraxane (albumin nanoparticle); and Genexol-PM (polymeric micelle). In the ex vivo dually perfused human placental cotyledon, placental accumulation of Genexol-PM is higher than Taxol, and both nanoformulations have lower maternal concentrations of paclitaxel over time. In vitro studies of these formulations and fluorescent nanoparticle analogs demonstrate that Genexol-PM allows paclitaxel to overcome P-glycoprotein efflux, but Abraxane behaves as a free drug formulation. We anticipate that these findings will impact future development of rational and safe treatment strategies for pregnancy-associated breast cancer and other diseases.”

PLGA from PolySciTech used in development of Gel-Microparticle Erlotinib delivery system for cancer therapy

 


Many therapeutic agents which are effective against cancer also have negative side effects in other parts of the body which leads to a need for a localized delivery system. Recently, researchers at University of California Los Angeles and Kangwon National University (Korea) used PLGA (AP045) from PolySciTech (www.polyscitech.com) to make ERT loaded microparticles for testing their cancer treatment potentials in a gel system. This research holds promise for improved cancer therapies. Read more: Lee, Song Yi, Mingyu Yang, Ji-Hye Seo, Da In Jeong, ChaeRim Hwang, Han-Jun Kim, Junmin Lee, KangJu Lee, JiHye Park, and Hyun-Jong Cho. "Serially pH-Modulated Hydrogels Based on Boronate Ester and Polydopamine Linkages for Local Cancer Therapy." ACS Applied Materials & Interfaces. https://pubs.acs.org/doi/abs/10.1021/acsami.0c16199

“Elaborately and serially pH-modulated hydrogels possessing optimized viscoelastic natures for short gelation time and single syringe injection were designed for peritumoral injection of an anticancer agent. Boronate ester bonds between phenylboronic acid (PBA) (installed in HA-PBA (HP)) and dopamine (included in HA-dopamine (HD)) along with self-polymerization of dopamine (via interactions between HD conjugates) were introduced as the main cross-linking strategies of a hyaluronic acid (HA) hydrogel. Considering pKa values (8.0–9.5) of PBA and dopamine, the pH of each polymer dispersion was controlled elaborately for injection through a single syringe, and the final pH was tuned nearby the physiological pH (pH 7.8). The shear-thinning behavior, self-healing property, and single syringe injectability of a designed hydrogel cross-linked nearby physiological pH may provide its convenient application to peritumoral injection and prolonged retention in local cancer therapy. Erlotinib (ERT) was encapsulated in a microsphere (MS), and it was further embedded in an HP/HD-based hydrogel for sustained and locoregional delivery. A rheologically tuned hydrogel containing an ERT MS exhibited superior tumor-suppressive efficiencies compared to the other groups in A549 tumor-bearing mice. A designed injectable hydrogel through a single syringe system may be efficiently applied to local cancer therapy with lower toxicities to healthy organs.”

PEG-PLGA from PolySciTech used in development of Parkinson’s disease therapy

 

Parkinson’s disease affects the nervous system and leads to decreased motor control. A treatment for this disease is Levodopa however this drug has cardiovascular side effects which makes targeted delivery preferable to system. Recently, researchers at Sun Yat-sen University (China), Ocean University of China, and Johns Hopkins University, Used mPEG-PLGA (AK101) from PolySciTech (www.polyscitech.com) to investigate nanoparticle formulations for treatment of Parkinson’s disease by delivery of levodopa. This research holds promise to improve therapies against Parkinson’s disease. Read more: Nie, Tianqi, Zhiyu He, Jinchang Zhu, Kuntao Chen, Gregory P. Howard, Jesus Pacheco-Torres, Il Minn et al. "Non-invasive delivery of levodopa-loaded nanoparticles to the brain via lymphatic vasculature to enhance treatment of Parkinson’s disease." Nano Research: 1-13. https://link.springer.com/article/10.1007/s12274-020-3280-0

“Abstract: Levodopa (L-DOPA), a precursor of dopamine, is commonly prescribed for the treatment of the Parkinson’s disease (PD). However, oral administration of levodopa results in a high level of homocysteine in the peripheral circulation, thereby elevating the risk of cardiovascular disease, and limiting its clinical application. Here, we report a non-invasive method to deliver levodopa to the brain by delivering L-DOPA-loaded sub-50 nm nanoparticles via brain-lymphatic vasculature. The hydrophilic L-DOPA was successfully encapsulated into nanoparticles of tannic acid (TA)/polyvinyl alcohol (PVA) via hydrogen bonding using the flash nanocomplexation (FNC) process, resulting in a high L-DOPA-loading capacity and uniform size in a scalable manner. Pharmacodynamics analysis in a PD rat model demonstrated that the levels of dopamine and tyrosine hydroxylase, which indicate the dopaminergic neuron functions, were increased by 2- and 4-fold, respectively. Movement disorders and cerebral oxidative stress of the rats were significantly improved. This formulation exhibited a high degree of biocompatibility as evidenced by lack of induced inflammation or other pathological changes in major organs. This antioxidative and drug-delivery platform administered through the brain-lymphatic vasculature shows promise for clinical treatment of the PD.”

Tuesday, January 12, 2021

PLGA from PolySciTech used for development of PEG-protected nanoparticles for enzyme delivery

 

The process of making nanoparticles is fundamentally rooted in precipitation of the polymer in aqeous phase to form the solid. There are a multitude of variables around how this is performed and which components (PLGA, PLGA-PEG, solvents, emulsifying agents) are used. Recently, researchers from University of Washington used PLGA (AP059) from PolySciTech (www.polyscitech.com) to create nanoparticles and study the processing sonication and other parameters on their resultant toxicity and enzyme carrying capabilities. This holds promise to gain futher understanding about the use of nanoparticles as enzymatic carriers. Read more: Liao, Rick, Jessica Pon, Michael Chungyoun, and Elizabeth Nance. "Enzymatic protection and biocompatibility screening of enzyme-loaded polymeric nanoparticles for neurotherapeutic applications." Biomaterials 257 (2020): 120238. https://www.sciencedirect.com/science/article/pii/S0142961220304841

“Abstract: Polymeric nanoparticles provide a non-invasive strategy for enhancing the delivery of labile hydrophilic enzymatic cargo for neurological disease applications. One of the most common polymeric materials, poly(lactic-co-glycolic acid) (PLGA) copolymerized with poly(ethylene glycol) (PEG) is widely studied due to its biocompatible and biodegradable nature. Although PLGA-PEG nanoparticles are generally known to be non-toxic and protect enzymatic cargo from degradative proteases, different formulation parameters including surfactant, organic solvent, sonication times, and formulation method can all impact the final nanoparticle characteristics. We show that 30s sonication double emulsion (DE)-formulated nanoparticles achieved the highest enzymatic activity and provided the greatest enzymatic activity protection in degradative conditions, while nanoprecipitation (NPPT)-formulated nanoparticles exhibited no protection compared to free catalase. However, the same DE nanoparticles also caused significant toxicity on excitotoxicity-induced brain tissue slices, but not on healthy or neuroinflammation-induced tissue. We narrowed the culprit of toxicity to specifically sonication of PLGA-PEG polymer with dichloromethane (DCM) as the organic solvent, independent of surfactant type. We also discovered that toxicity was oxidative stress-dependent, but that increased toxicity was not enacted through increasing oxidative stress. Furthermore, no PEG degradation or aldehyde, alcohol, or carboxylic acid functional groups were detected after sonication. We identified that inclusion of free PEG along with PLGA-PEG polymer during the emulsification phases or replacing DCM with trichloromethane (chloroform) produced biocompatible polymeric nanoparticle formulations that still provided enzymatic protection. This work encourages thorough screening of nanoparticle toxicity and cargo-protective capabilities for the development of enzyme-loaded polymeric nanoparticles for the treatment of disease.”

PLGA from PolySciTech used in development of localized microparticle arthritis treatment

 

Arthritis is a disease in which the cartilage of joints is damaged by immune response as well as trauma and age which leads to damage of chondrocytes. Rapamycin has the ability to help chondrocytes heal cartilage but is limited in use due to systemic toxicity. Recently, researchers at Indian Institute of Science used PLGA (AP041) from PolySciTech (www.polyscitech.com) to create microparticles for localized rapamycin delivery to joint tissue. This research holds promise to provide for improved therapies against arthritis. Read more: Dhanabalan, Kaamini M., Vishal K. Gupta, and Rachit Agarwal. "Rapamycin–PLGA microparticles prevent senescence, sustain cartilage matrix production under stress and exhibit prolonged retention in mouse joints." Biomaterials science 8, no. 15 (2020): 4308-4321. https://pubs.rsc.org/no/content/articlehtml/2020/bm/d0bm00596g

“Osteoarthritis (OA) is a joint disease characterized by progressive damage of articular cartilage and the adjoining subchondral bone. Chondrocytes, the primary cells of the cartilage, have limited regenerative capacity and when they undergo stress due to trauma or with aging, they senesce or become apoptotic. Rapamycin, a potent immunomodulator, has shown promise in OA treatment. It activates autophagy and is known to prevent senescence. However, its clinical translation for OA is hampered due to systemic toxicity as high and frequent doses are required. Here, we have fabricated rapamycin encapsulated poly(lactic-co-glycolic acid) (PLGA) based carriers that induced autophagy and prevented cellular senescence in human chondrocytes. The microparticle (MP) delivery system showed sustained release of the drug for several weeks. Rapamycin microparticles protected in vitro cartilage mimics (micromass cultures) from degradation, allowing sustained production of sGAG, and demonstrated a prolonged senescence preventive effect under oxidative and genomic stress conditions. These microparticles also exhibited a residence time of ∼30 days after intra-articular injections in murine knee joints. Such particulate systems are promising candidates for intra-articular delivery of rapamycin for the treatment of osteoarthritis.”