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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N3-PEG-PLGA, Fluorescent-PLGAs from PolySciTech used in development of targeted nanoparticles as part of cancer immunotherapy

Wednesday, July 8, 2020, 3:29 PM ET

Immunotherapy against cancer is a promising field in which the human body’s own immune system is used to target the cancer directly. Recently, researchers at University of North Carolina at Chapel Hill and Levine Cancer Institute used N3-PEG-PLGA (AI091), PEG-PLGA (AK104), FITC-PLGA (AV016), and CY5-PLGA (AV032) from PolySciTech (www.polyscitech.com) to produce targeted nanoparticles to target immune cells and induce them to attack cancer cells. This research holds promise to provide for improved therapies against this fatal class of diseases. Read more: Au, Kin Man, Steven I. Park, and Andrew Z. Wang. "Trispecific natural killer cell nanoengagers for targeted chemoimmunotherapy." Science Advances 6, no. 27 (2020): eaba8564. https://advances.sciencemag.org/content/6/27/eaba8564.abstract

“Abstract: Activation of the innate immune system and natural killer (NK) cells has been a key effort in cancer immunotherapy research. Here, we report a nanoparticle-based trispecific NK cell engager (nano-TriNKE) platform that can target epidermal growth factor receptor (EGFR)–overexpressing tumors and promote the recruitment and activation of NK cells to eradicate these cancer cells. Moreover, the nanoengagers can deliver cytotoxic chemotherapeutics to further improve their therapeutic efficacy. We have demonstrated that effective NK cell activation can be achieved by the spatiotemporal coactivation of CD16 and 4-1BB stimulatory molecules on NK cells with nanoengagers, and the nanoengagers are more effective than free antibodies. We also show that biological targeting, either through radiotherapy or EGFR, is critical to the therapeutic effects of nanoengagers. Last, EGFR-targeted nanoengagers can augment both NK-activating agents and chemotherapy (epirubicin) as highly effective anticancer agents, providing robust chemoimmunotherapy.”

PLGA from PolySciTech used in development of treatment for MRSA infected wounds

Wednesday, July 8, 2020, 3:27 PM ET

Methicillin-resistant Staphylococcus aureus (MRSA) is a wound-infecting pathogen that leads to significant causes of morbidity and mortality which is difficult to treat due to its resistance against most common antibiotics. Recently, researchers at Pusan National University (Korea) used PLGA (AP037) from PolySciTech (www.poyscitech.com) to develop nitrosoglutathione delivery nanoparticles to provide for treatment against wound infection. This research holds promise to provide for more effective treatments against MRSA infections in the future. Read more: Lee, Juho, Dongmin Kwak, Hyunwoo Kim, Jihyun Kim, Shwe Phyu Hlaing, Nurhasni Hasan, Jiafu Cao, and Jin-Wook Yoo. "Nitric Oxide-Releasing S-Nitrosoglutathione-Conjugated Poly (Lactic-Co-Glycolic Acid) Nanoparticles for the Treatment of MRSA-Infected Cutaneous Wounds." Pharmaceutics 12, no. 7 (2020): 618.

“Abstract: S-nitrosoglutathione (GSNO) has emerged as a potent agent for the treatment of infected cutaneous wounds. However, fabrication of GSNO-containing nanoparticles has been challenging due to its high hydrophilicity and degradability. The present study aimed to fabricate nanoparticles using newly synthesized GSNO-conjugated poly(lactic-co-glycolic acid) (PLGA) (GSNO-PLGA; GPNPs). Since hydrophilic GSNO was covalently bound to hydrophobic PLGA, loss of GSNO during the nanoparticle fabrication process was minimized, resulting in sufficient loading efficiency (2.32% of GSNO, 0.07 μmol/mg of NO). Real-time NO release analysis revealed biphasic NO release by GPNPs, including initial burst release within 3 min and continuous controlled release for up to 11.27 h, due to the differential degradation rates of the –SNO groups located at the surface and inside of GPNPs. Since GPNPs could deliver NO more efficiently than GSNO in response to increased interaction with bacteria, the former showed enhanced antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA) at the same equivalent concentrations of NO. Finally, the facilitating effects of GPNPs on infected wound healing were demonstrated in MRSA-challenged full-thickness wound mouse model. Collectively, the results suggested GPNPs as an ideal nanoparticle formulation for the treatment of MRSA-infected cutaneous wounds. Keywords: S-nitrosoglutathione (GSNO); poly(lactic-co-glycolic acid) (PLGA); nitric oxide; nitric oxide-releasing nanoparticles; GSNO-conjugated PLGA; methicillin-resistant Staphylococcus aureus (MRSA); infected wound healing”

PLGA-PEG-PLGA Thermogel used in Ocular Drug Delivery Application

Wednesday, July 8, 2020, 3:26 PM ET

There are many diseased which affect the eyes and can lead to blindness including secondary cataracts. Delivery of medicines to the ocular region is difficult due to limited flow. Recently, researchers at Rowan University used PLGA-PEG-PLGA (AK097) from PolySciTech (www.polyscitech.com) to create an injectable ocular gel for drug delivery applications. This research holds promise to prevent disease-related blindness. Read more: Osorno, Laura L. "Novel injectable PLGA-PEG-PLGA self-assembled hydrogels for the extended and controlled release of DNA nanocarriers to prevent secondary cataracts." Rowan University PhD Thesis (2020). https://rdw.rowan.edu/etd/2822/

“Cataracts are the second leading cause of blindness worldwide. There are over 20 million cataract surgeries each year, and these cases are expected to double within the next ten years. Over 40% of adults and nearly all children develop secondary cataracts, or posterior capsule opacification (PCO), following cataract surgery. Currently, Nd:YAG laser therapy is used to treat PCO; however, laser therapy is not available worldwide and treatment may have adverse effects on surrounding ocular tissues. Thus, there is a considerable unmet need for more efficacious and convenient treatments to prevent PCO. Injectable, stimuli-responsive gels were designed using poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)) triblock copolymer and poly(L-Lysine). Hydrogel formulations with lactic acid to glycolic acid ratio of 15/1, at compositions between 14 and 25% (w/v), PLGA/PEG ratio of 2/1, and PLL concentrations between 10 and 40% (w/v) allowed for over 90% light transmittance, gel formation at 35 °C, and controlled release of 3DNA® nanocarriers loaded with doxorubicin with the G8 monoclonal antibody conjugated (3DNA®:DOX:G8) for over four weeks. The physical and morphological states of this novel, thermo-sensitive hydrogel can be easily tailored for the purpose of modulating drug delivery utilizing nucleic acids. This technology offers a more effective and efficient method of ocular therapy by providing controlled delivery of 3DNA conjugates designed to specifically target cells that cause PCO. Our US patent pending technology has high potential as a more efficacious delivery method for a wide range of other therapeutics to treat a number of ocular diseases.”

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

Tuesday, June 30, 2020, 9:11 AM ET

Liver cancer is a very common and often fatal form of cancer that has limited treatment options outside of surgical resection. Recently, researchers at Johns Hopkins University utilized mPEG-PLGA (AK037) from PolySciTech (www.polyscitech.com) to create bortezomib-loaded nanoparticles as a treatment option for liver cancer. This research holds promise for improved therapies against this fatal disease. Read more: Zhou, Yang. "Development of Bortezomib-Loaded Nanoparticles for Locoregional Treatment of Hepatocellular Carcinoma." PhD diss., Johns Hopkins University, 2020. https://jscholarship.library.jhu.edu/handle/1774.2/62729

“Abstract: Hepatocellular carcinoma (HCC) is the 6th most common cancer and the 4th leading cause of carcinoma-related death worldwide; yet there no curative chemotherapy strategy available for unresectable HCC. Bortezomib (BTZ) is a proteasome inhibitor that is FDA-approved for multiple myeloma and certain subtypes of chronic myelogenous leukemia; and in drug screening tests it shows promising potency in HCC cells. Systemic administration at required doses proves to be toxic in mice, however, repeated intra-tumoral injections results in tumor regression. The objective of this study is to develop a BTZ-loaded nanoparticle that can lower the systemic toxicity through local release of BTZ over several days. The BTZ-loaded nanoparticles were prepared by a facile assembly technique combining flash nanocomplexation (FNC) and flash nanoprecipitation (FNP), achieving high uniformity, stability, and adjustability by controlling the input parameters during preparation process. In the pilot in vivo study, the BTZ-loaded nanoparticles demonstrated local retention for more than 10 days in tumor tissue following intratumoral injection and exerted similar tumor-killing effect with same dose, yet less injection frequency as compared to free BTZ. The BTZ-loaded nanoparticles exhibited potential as a locoregional delivery system to provide a new therapeutic modality for future HCC treatment”

Mal-PEG-PLGA from PolySciTech used in development of bevacizumab-nanoparticle based therapy for treatment of colorectal cancer

Friday, June 26, 2020, 10:00 AM ET

Colorectal cancer is one of the most common cancers in the world and is very difficult to treat effectively. Recently, Researchers at i3S, INEB, and Universidade do Porto (Portugal) used PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) as part of development of targeted nanoparticles loaded with bevacizumab to treat colon cancer. This research holds promise to improve therapies against this disease. Read more: Baião, Ana, Flávia Sousa, Ana Vanessa Oliveira, Carla Oliveira, and Bruno Sarmento. "Effective intracellular delivery of bevacizumab via PEGylated polymeric nanoparticles targeting the CD44v6 receptor in colon cancer cells." Biomaterials Science (2020). https://pubs.rsc.org/en/content/articlelanding/2020/bm/d0bm00556h/unauth#!divAbstract

“Abstract: Colorectal cancer (CRC) is one of the most common and deadly cancers in the world, mainly due to its metastatic and metabolic ability. The CD44 receptor isoform containing exon 6 (CD44v6) is a transmembrane protein that plays an important role in the establishment of tumors and metastasis, which make this molecule a potential target for therapy and diagnosis of tumors. Aiming at a targeted therapy, the anti-VEGF monoclonal antibody (mAb) bevacizumab was loaded into poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) functionalized with an antibody fragment (Fab) specific for CD44v6-expressing human cancer cells. The sizes of NPs were in the range of 150–250 nm and they had a negative charge between −5 and −10 mV, with an association efficiency (AE) of bevacizumab of 86%. v6 Fab-PLGA-PEG NPs containing bevacizumab specifically bonded to the CD44v6 cell surface receptor and exhibited higher internalization into CD44v6+ epithelial cells than bare and (−) Fab-PLGA-PEG NPs. To understand the biological effect of NP targeting, the intracellular levels of bevacizumab and VEGF were evaluated after the incubation of targeted and untargeted NPs. The intracellular levels of bevacizumab were significantly higher in cells incubated with v6 Fab-PLGA-PEG NPs and these NPs resulted in a significant decrease in the intracellular VEGF compared to untargeted NPs and free bevacizumab. PLGA-PEG NPs, surface-functionalized with a v6-specific Fab, have the potential to intracellularly deliver bevacizumab into CD44v6 expressing cancer cells.”

PLGA from PolySciTech used in development of laser-activated ocular delivery implant

Monday, June 22, 2020, 4:27 PM ET

Several chronic ocular diseases can be treated by direct delivery of medicinal molecules into the ocular space. However, performing repeat ocular injections is inconvenient for both patient and practitioner. Recently, researchers at University of Cincinnati used PLGA (AP049) from PolySciTech (www.polyscitech.com) to create a laser-triggered implant for delivery of controlled dosage drugs against macular degeneration and other ocular diseases. This research holds promise to prevent blindness. Read more: He, Xingyu, Zheng Yuan, Samantha Gaeke, Winston W. Kao, Daniel Miller, Basil Williams, and Yoonjee Park. "Laser-activated drug implant for controlled release to the posterior segment of the eye." bioRxiv (2020). https://www.biorxiv.org/content/10.1101/2020.06.17.111641v1.abstract

“Abstract: Posterior segment eye diseases such as age-related macular degeneration (AMD), diabetic macular edema (DME) and proliferative vitreoretinopathy (PVR) are serious choric diseases that may result in vision loss. The current standard of care for the posterior segment eye diseases involves frequent intravitreal injections or intravitreally injectable sustained-release implants. However, dosage is not controllable once the implant is inserted in the vitreous, resulting in serious local side effects, such as elevated intraocular pressure and cataract formation. We previously developed a size-exclusive nanoporous biodegradable PLGA capsule and combined with light-activatable drug-encapsulated liposomes, to create a lightactivated dose-controllable implant for posterior eye disease treatment. We demonstrated the stability and safety of the implant in rabbit eyes for 6 months. In this study, we focused on the drug release from the dose-controllable implant by laser irradiation both in vitro and in vivo. Drug release kinetics upon laser irradiation were analyzed with two different total dosages. Drug release by laser irradiation in the rabbit eyes was determined by fluorescence intensity. Optical and histology examination confirmed no damage on the retina. The results demonstrated feasibility of using the implant as a on-demand dose-controllable drug delivery system to the posterior segment of the eye.”

PLGA from PolySciTech used in development of Rifampicin-loaded nanoparticles for tuberculosis treatment with reduced liver toxicity

Wednesday, June 10, 2020, 1:50 PM ET

Some medicines are limited in their usefulness due to their organ-specific toxic side-effects. Notably, rifampicin, an antibiotic against tuberculosis, has liver toxicity which limits the quantity which can be prescribed. Recently, researchers at Assiut University (Egypt) and University of Cincinnati (USA) used PLGA (AP104) from PolySciTech (www.polyscitech.com) to provide for nanoparticle delivery system of rifampicin with reduced liver toxicity. This research holds promise to improve treatment of tuberculosis. Read more: Hetta, Helal F., Esraa A. Ahmed, Ahmed G. Hemdan, Heba EM El-Deek, Saida Abd-Elregal, and Noura H. Abd Ellah. "Modulation of rifampicin-induced hepatotoxicity using poly (lactic-co-glycolic acid) nanoparticles: a study on rat and cell culture models." Nanomedicine 0 (2020). https://www.futuremedicine.com/doi/abs/10.2217/nnm-2020-0001

“Aim: Hepatotoxicity is the most serious adverse effect of rifampicin (RIF). We aimed to investigate the potential hepatoprotective effect of mannose-functionalized poly(lactic-co-glycolic acid)(PLGA)/RIF nanoparticles (NPs) in rats as a possible promising approach to minimize RIF-induced hepatotoxicity. Materials & methods: Mannose-functionalized PLGA/RIF NPs were fabricated and characterized in vitro, then the hepatoprotective effect of optimized NPs was studied on rat and cell culture models. Results: Following intraperitoneal administration of RIF NPs into rats, highly significant differences in levels of serum transaminases and oxidative stress markers, associated with significant differences in expression of Bax and Bcl-2 genes between NPs- and free RIF-treated groups, revealing the hepatoprotective potential of NPs. Conclusion: RIF NPs may represent a promising therapeutic approach for tuberculosis via reducing dose frequency and consequently, RIF-induced hepatotoxicity. Keywords: hepatotoxicity mannose nanoparticles PLGA rifampicin tuberculosis”

PLGA-PEG-NHS/PLGA-PEG-COOH from PolySciTech used in development of nanoparticles for pancreatic cancer treatment

Wednesday, June 10, 2020, 1:47 PM ET

In the early stages of development, pancreatic cancer presents relatively little in terms of symptoms which unfortunately makes it very difficult to detect until later stages when it may be too late to effectively treat. This means pancreatic cancer treatment requires aggressive interventions and targeting in order to be effective. Recently, researchers at Queen's University Belfast, Dublin City University (Ireland), State University of New York, and Roswell Park Comprehensive Cancer Center (USA) used PLGA-PEG-NHS (AI064) and PLGA-PEG-COOH (AI034) from PolySciTech (www.polyscitech.com) to produce targeted nanoparticles against pancreatic cancer. This research holds promise to provide for improved therapies against this often fatal form of cancer in the future. Read more: Johnston, M.C., Nicoll, J.A., Redmond, K.M., Smyth, P., Greene, M.K., McDaid, W.J., Chan, D.K.W., Crawford, N., Stott, K.J., Fox, J.P. and Straubinger, N.L., 2020. DR5-targeted, chemotherapeutic drug-loaded nanoparticles induce apoptosis and tumor regression in pancreatic cancer in vivo models. Journal of Controlled Release. https://www.sciencedirect.com/science/article/pii/S0168365920303230

“Highlights: The death receptor 5 pathway is upregulated in pancreatic cancer and correlates with poorer prognosis. Conjugation of AMG 655 to the nanoparticle surface renders it capable of inducing apoptosis via death receptor 5 in pancreatic cancer cell lines. FLIP downregulation increases response to TRAIL and nanoparticle conjugated AMG 655. Camptothecin entrapment causes downregulation of FLIP. CRISPR targeting shows conjugated AMG 655 efficacy is FADD and caspase 8 dependent. Abstract: Pancreatic cancer is usually advanced and drug resistant at diagnosis. A potential therapeutic approach outlined here uses nanoparticle (NP)-based drug carriers, which have unique properties that enhance intra-tumor drug exposure and reduce systemic toxicity of encapsulated drugs. Here we report that patients whose pancreatic cancers express elevated levels of Death Receptor 5 (DR5) and its downstream regulators/effectors FLIP, Caspase-8, and FADD had particularly poor prognoses. To take advantage of elevated expression of this pathway, we designed drug-loaded NPs with a surface-conjugated αDR5 antibody (AMG 655). Binding and clustering of the DR5 is a prerequisite for efficient apoptosis initiation, and the αDR5-NPs were indeed found to activate apoptosis in multiple pancreatic cancer models, whereas the free antibody did not. The extent of apoptosis induced by αDR5-NPs was enhanced by down-regulating FLIP, a key modulator of death receptor-mediated activation of caspase-8. Moreover, the DNA topoisomerase-1 inhibitor camptothecin (CPT) down-regulated FLIP in pancreatic cancer models and enhanced apoptosis induced by αDR5-NPs. CPT-loaded αDR5-NPs significantly increased apoptosis and decreased cell viability in vitro in a caspase-8- and FADD-dependent manner consistent with their expected mechanism-of-action. Importantly, CPT-loaded αDR5-NPs markedly reduced tumor growth rates in vivo in established pancreatic tumor models, inducing regressions in one model. These proof-of-concept studies indicate that αDR5-NPs loaded with agents that downregulate or inhibit FLIP are promising candidate agents for the treatment of pancreatic cancer.”

Mal-PEG-PLGA/PEG-PLGA from PolySciTech used in development of nanoparticle-adjuvant vaccines

Wednesday, June 10, 2020, 1:46 PM ET

Vaccines act to induce the human immune system to recognize and attack pathogens preventing future infections. The role of an adjuvant in a vaccine is to ensure that the appropriate immune response is elicited by the vaccine to provide for the protection. Recently, researchers at Royal Melbourne Institute of Technology, Monash University (Australia), Johns Hopkins School of Medicine, and University of Florida used mPEG-PLGA (AK101) and Mal-PEG-PLGA (AI109) from PolySciTech (www.polyscitech.com) to create nanoparticles for immune response. This research holds promise to enable the development of more effective vaccine strategies. Read more: Wilson, Kirsty L., Gregory P. Howard, Heather Coatsworth, Rhoel R. Dinglasan, Hai-Quan Mao, and Magdalena Plebanski. "Biodegradable PLGA-b-PEG Nanoparticles Induce T Helper 2 (Th2) Immune Responses and Sustained Antibody Titers via TLR9 Stimulation." Vaccines 8, no. 2 (2020): 261. https://www.mdpi.com/2076-393X/8/2/261

“Abstract: Sustained immune responses, particularly antibody responses, are key for protection against many endemic infectious diseases. Antibody responses are often accompanied by T helper (Th) cell immunity. Herein we study small biodegradable poly (ethylene glycol)-b-poly (lactic-co-glycolic acid) nanoparticles (PEG-b-PLGA NPs, 25–50 nm) as antigen- or adjuvant-carriers. The antigen carrier function of PEG-b-PLGA NPs was compared against an experimental benchmark polystyrene nanoparticles (PS NPs, 40–50 nm), both conjugated with the model antigen ovalbumin (OVA-PS NPs, and OVA-PEG-b-PLGA NPs). The OVA-PEG-b-PLGA NPs induced sustained antibody responses to Day 120 after two immunizations. The OVA-PEG-b-PLGA NPs as a self-adjuvanting vaccine further induced IL-4 producing T-helper cells (Th2), but not IFN-γ producing T-cells (Th1). The PEG-b-PLGA NPs as a carrier for CpG adjuvant (CpG-PEG-b-PLGA NPs) were also tested as mix-in vaccine adjuvants comparatively for protein antigens, or for protein-conjugated to PS NPs or to PEG-b-PLGA NPs. While the addition of this adjuvant NP did not further increase T-cell responses, it improved the consistency of antibody responses across all immunization groups. Together these data support further development of PEG-b-PLGA NPs as a vaccine carrier, particularly where it is desired to induce Th2 immunity and achieve sustained antibody titers in the absence of affecting Th1 immunity. Keywords: nanoparticle; adjuvant; vaccine; antibody; immune response”

Thermogelling PLGA-PEG-PLGA from PolySciTech used in development of ocular treatment against secondary cataract formation

Tuesday, June 2, 2020, 10:15 AM ET

Cataracts are a common ocular problem and can lead to blindness. Unfortunately, even after cataract removal, there is a common incidence of secondary cataracts which can also obstruct vision. Recently, researchers at Rowan University used PLGA-PEG-PLGA (AK097) from PolySciTech (www.polyscitech.com) to develop an ocular Thermogel system for treatment of secondary cataracts. This research holds promise to improve therapies against development of blindness even after cataract removal. Read more: Osorno, Laura L., Jamie DR Medina, Daniel E. Maldonado, Robert J. Mosley, and Mark E. Byrne. "Extended Release of Doxorubicin-Loaded 3DNA Nanocarriers from In-Situ Forming, Self-Assembled Hydrogels." Journal of Ocular Pharmacology and Therapeutics (2020). https://www.liebertpub.com/doi/abs/10.1089/jop.2019.0145

“Purpose: Cataracts are the leading cause of blindness worldwide, resulting in over 30 million surgeries each year. These cases are expected to double within the next 10 years. About 25% of all patients develop secondary cataracts or posterior capsule opacification (PCO) postsurgery. PCO is a vision impairment disorder that develops from myofibroblasts migration and contraction that deforms the capsule surrounding the lens. Currently, Nd:YAG laser therapy is used to treat PCO; however, laser is not available worldwide and adverse side effects may arise. Thus, there is a considerable unmet need for more efficacious and convenient preventive treatments for PCO. Our work focuses on engineering an innovative, prophylactic sustained release platform for DNA-based nanocarriers to further reduce the incidence of PCO. Methods: Novel, optically clear, self-assembled poly(d,l-lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-PEG) triblock copolymer hydrogels were used for the sustained release of the DNA-based nanocarriers (3DNA®) loaded with cytotoxic doxorubicin (DOX) and targeted with a monoclonal antibody called G8 (3DNA:DOX:G8), which is specific to cells responsible for PCO. Results: The 29 (w/v)% polymer hydrogels with the 3DNA nanocarriers presented over 80% of light transmittance, soft mechanical properties (

PLGA from PolySciTech used in research on Polymer-Magnesium composite stents for treatment of heart disease

Wednesday, May 27, 2020, 2:45 PM ET

Heart disease is the leading cause of death in USA and is often characterized by closing of arteries feeding oxygenated blood to the heart leading to a heart attack. Non-resorbable stents have been applied to hold the vessels open, but these have drawbacks for long-term usage due to tissue reaction against the stents leading to reclosure of the vessel. Recently, researchers at University of California Riverside used PLGA (AP089) from PolySciTech (www.polyscitech.com) to create polymer-magnesium composite vascular stents for use in treatment of heart disease. This research holds promise to improve cardiovascular therapies in the future. Read more: Jiang, Wensen, Chaoxing Zhang, Larry Tran, Sebo Gene Wang, Ammar Dilshad Hakim, and Huinan Hannah Liu. "Engineering Nano-to-micron Patterned Polymer Coatings on Bioresorbable Magnesium for Controlling Human Endothelial Cell Adhesion and Morphology." ACS Biomaterials Science & Engineering (2020). https://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.0c00642

“Abstract: Surface patterning is an attractive approach to modify the surface of biomaterials for modulating cell activities and enhancing performance of medical implants without involving typical chemical changes to the implants such as adding growth factors, antibiotics, and drugs. In this study, nano-to-micron patterns were engineered on thermoplastic and thermoset polymer coatings on bioresorbable magnesium (Mg) substrates to control the cellular responses and material degradation, for vascular applications. Capillary force lithography (CFL) was modified and integrated with spray coating to fabricate well-aligned nano-to-micron patterns on the thermoplastic poly(lactic-co-glycolic acid) (PLGA) and thermoset poly(glycerol sebacate) (PGS) coatings on Mg substrates. Specifically, a new process of molding-curing CFL was revised from the conventional CFL to successfully create nano-to-submicron patterns on thermoset PGS for the first time. The nano-to-micron patterned polymer coatings of PLGA and PGS on Mg were carefully characterized, and their effects on cell adhesion and morphology were investigated through direct culture with human umbilical vein endothelial cells (HUVECs) in vitro. The results showed that the 3000-nm parallel grooves could effectively elongate the HUVECs while the 740-nm parallel grooves tended to reduce the spreading of HUVECs. The PLGA coatings reduced the degradation of Mg substrates more than that of the PGS coatings in the direct culture with HUVECs in vitro. CFL-based methods coupled with spray coating should be further studied as a non-chemical approach for creating nano-to-micron patterned polymer coatings on Mg-based substrates of various size and shape, which may present a new direction for improving the performance of Mg-based bioresorbable vascular devices toward potential clinical translation.”

PLGA from PolySciTech used in development of Rapamycin-delivery microparticles for arthritis treatment

Wednesday, May 13, 2020, 3:09 PM ET

Arthritis is a disease driven by several causes but categorized by an immune response in the cartilidge which leads to damage of the tissue. Rapamycin modulates this immune response and can reduce the progression of arthritis. Recently, researchers at Indian Institute of Science (India) used PLGA (AP041) from PolySciTech (www.polyscitech.com) to develop Rapamycin-releasing microparticles. This research holds promise to provide for treatment against arthritis. Read more: Dhanabalan, Kaamini M., Vishal K. Gupta, and Rachit Agarwal. "Rapamycin-PLGA microspheres induce autophagy and prevent senescence in chondrocytes and exhibit long in vivo residence." bioRxiv (2020). https://www.biorxiv.org/content/10.1101/2020.04.06.027136v1.abstract

“Osteoarthritis (OA) is a joint disease that results in progressive destruction of articular cartilage and the adjoining subchondral bone. The current treatment is focused on symptomatic relief due to the absence of disease-modifying drugs. The primary cells of the cartilage, chondrocytes, have limited regenerative capacity and when they undergo stress due to trauma or with aging, they senesce or become apoptotic. Autophagy, a cellular homeostasis mechanism has a protective role in OA during stress but gets downregulated in OA. Rapamycin, a potent immunomodulator, has shown promise in OA treatment by autophagy activation 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. Hence, there is a need to develop suitable delivery carriers that can result in sustained and controlled release of the drug in the joint. In this study, 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 drug for several weeks. Rapamycin-microparticles protected in-vitro cartilage mimics from degradation, allowing sustained production of sGAG, and demonstrated a prolonged senescence preventive effect in vitro under oxidative and genomic stress conditions. These microparticles also exhibited a long residence time of more than 19 days in the joint after intra-articular injections in murine knee joints. Such particulate systems are a promising candidate for intra-articular delivery of rapamycin for treatment of osteoarthritis.”

PLGA-PEG-NH2 from PolySciTech used in development of photodynamic/x-ray therapy against colorectal cancer

Wednesday, May 13, 2020, 11:53 AM ET

Researchers at University of New South Wales, The University of Sydney, and Macquarie University (Australia) used PLGA-PEG-NH2 (AI058) from PolySciTech (www.polyscitech.com) to create photosentizing nanoparticles to apply in conjunction with X-ray therapy to treat cancer cells. This research holds promise to provide for improved cancer therapies. Read more: Deng, Wei, Kelly J. McKelvey, Anna Guller, Alexey Fayzullin, Jared M. Campbell, Sandhya Clement, Abbas Habibalahi et al. "Application of Mitochondrially Targeted Nanoconstructs to Neoadjuvant X-ray-Induced Photodynamic Therapy for Rectal Cancer." ACS Central Science (2020). https://pubs.acs.org/doi/abs/10.1021/acscentsci.9b01121

“In this work, we brought together two existing clinical techniques used in cancer treatment—X-ray radiation and photodynamic therapy (PDT), whose combination termed X-PDT uniquely allows PDT to be therapeutically effective in deep tissue. To this end, we developed mitochondrially targeted biodegradable polymer poly(lactic-co-glycolic acid) nanocarriers incorporating a photosensitizer verteporfin, ultrasmall (2–5 nm) gold nanoparticles as radiation enhancers, and triphenylphosphonium acting as the mitochondrial targeting moiety. The average size of the nanocarriers was about 160 nm. Upon X-ray radiation our nanocarriers generated cytotoxic amounts of singlet oxygen within the mitochondria, triggering the loss of membrane potential and mitochondria-related apoptosis of cancer cells. Our X-PDT strategy effectively controlled tumor growth with only a fraction of radiotherapy dose (4 Gy) and improved the survival rate of a mouse model bearing colorectal cancer cells. In vivo data indicate that our X-PDT treatment is cytoreductive, antiproliferative, and profibrotic. The nanocarriers induce radiosensitization effectively, which makes it possible to amplify the effects of radiation. A radiation dose of 4 Gy combined with our nanocarriers allows equivalent control of tumor growth as 12 Gy of radiation, but with greatly reduced radiation side effects (significant weight loss and resultant death).”

PLGA from PolySciTech used in development of nanoparticle therapy for skin cancer

Wednesday, May 13, 2020, 11:52 AM ET

Photodynamic therapy is a process in which cancer cells are targeted with a chemical substance that remains dormant until it is illuminated by a specific wavelength of light which activates it killing the cell. This two-step process minimizes damage to healthy cells which is a common side-effect of conventional chemotherapy. Recently, researchers at Wroclaw University (Poland) used PLGA (AP022) from PolySciTech (www.polyscitech.com) to develop photosensitizing nanoparticles which are uptaken into melanoma (skin cancer) cells. This research holds promise to provide for improved cancer therapies in the future. Read more: Bazylińska, Urszula, Dominika Wawrzyńczyk, Anna Szewczyk, and Julita Kulbacka. "Engineering and biological assessment of double core nanoplatform for co-delivery of hybrid fluorophores to human melanoma." Journal of Inorganic Biochemistry (2020): 111088. https://www.sciencedirect.com/science/article/pii/S0162013420301161

“Abstract: We investigated new development in photodynamic therapy (PDT) aiming at enhanced tumor selectivity and biocompatibility, which included application of a third-generation photosensitizing agent, i.e. xanthene-origin Rose Bengal (RB) co-encapsulated with up-converting NaYF4 nanoparticles (NPs) co-doped with lanthanide ions: Er3+ (2%) and Yb3+ (20%). The hybrid fluorophores were applied as components of double core nanocarriers (NCs) obtained by double (multiple) emulsion solvent evaporation process. Next to improve the biocompatibility and photodynamic activity, biodegradable polymer: poly(lactide-co-glycolide) – PLGA and non-ionic surfactants with different hydrophobicity: Span 80 and Cremophor A25, were used. After the engineering process, controlled by dynamic light scattering (DLS) measurements, ζ-potential evaluation, transmission electron and atomic force microscopy (TEM and AFM) imaging, as well as optical analysis provided by measurements of the up-conversion emission spectra and luminescence kinetics for encapsulated only NaYF4:Er3+,Yb3+ NPs and co-encapsulated RB + NaYF4:Er3+,Yb3+ molecules, spherical polyester NCs with average size

PLGA, PLGA-NH2, PLGA-NHS from PolySciTech used in development of brain-cancer treating nanoparticle

Wednesday, May 13, 2020, 11:51 AM ET

Glioblastoma (a form of brain cancer) is often a fatal disease with poor prognosis. Recently, researchers at Indiana University Purdue University Indianapolis (IUPUI) used PLGA (AP060), PLGA-NH2 (AI062), and PLGA-NHS (AI116) from PolySciTech (www.polyscitech.com) to create temozolomide loaded nanoparticles for brain-cancer therapy. This research holds promise to provide for improved therapy against this fatal disease. Read more: Smiley, Shelby B. "Targetable Multi-Drug Nanoparticles for Treatment of Glioblastoma with Neuroimaging Assessment." PhD dissertation, IUPUI, 2020. https://scholarworks.iupui.edu/handle/1805/22683

“Glioblastoma (GBM) is a deadly, malignant brain tumor with a poor long-term prognosis. The current median survival is approximately fifteen to seventeen months with the standard of care therapy which includes surgery, radiation, and chemotherapy. An important factor contributing to recurrence of GBM is high resistance of GBM cancer stem cells (CSCs), for which a systemically delivered single drug approach will be unlikely to produce a viable cure. Therefore, multi-drug therapies are needed. Currently, only temozolomide (TMZ), which is a DNA alkylator, affects overall survival in GBM patients. CSCs regenerate rapidly and over-express a methyl transferase which overrides the DNA-alkylating mechanism of TMZ, leading to drug resistance. Idasanutlin (RG7388, R05503781) is a potent, selective MDM2 antagonist that additively kills GBM CSCs when combined with TMZ. By harnessing the strengths of nanotechnology, therapy can be combined with diagnostics in a truly theranostic manner for enhancing personalized medicine against GBM. The goal of this thesis was to develop a multi-drug therapy using multi-functional nanoparticles (NPs) that preferentially target the GBM CSC subpopulation and provide in vivo preclinical imaging capability. Polymer-micellar NPs composed of poly(styrene-b-ethylene oxide) (PS-b-PEO) and poly(lactic-co-glycolic) acid (PLGA) were developed investigating both single and double emulsion fabrication techniques as well as combinations of TMZ and RG7388. The NPs were covalently bound to a 15 base-pair CD133 aptamer in order to target a specific epitope on the CD133 antigen expressed on the surface of GBM CSC subpopulation. For theranostic functionality, the NPs were also labelled with a positron emission tomography (PET) radiotracer, zirconium-89 (89Zr). The NPs maintained a small size of less than 100 nm, a relatively neutral charge and exhibited the ability to produce a cytotoxic effect on CSCs. There was a slight increase in killing with the aptamer-bound NPs compared to those without a targeting agent. This work has provided a potentially therapeutic option for GBM specific for CSC targeting and future in vivo biodistribution studies.”

PLGA-Rhodamine B from PolySciTech used in development of novel macrophage-training immunotherapy cancer treatment

Wednesday, May 13, 2020, 11:50 AM ET

Cancer cells apply a wide range of biochemical methods of avoiding detection and elimination by the human immune system. Immunotherapy is a process by which the existing human immune system is induced to seek out and destroy cancer cells and stands as one of the most promising therapeutic approaches today. Recently, researchers at Harvard University used fluorescent PLGA-Rhodamine (AV011) from PolySciTech (www.polyscitech.com) to develop traceable particle backpacks which adhere to macrophages (immune cells) and induce the immune cells to attack cancer cells. This research holds promise to provide for a new treatment option against cancer. Read more: Shields, C. Wyatt, Michael A. Evans, Lily Li-Wen Wang, Neil Baugh, Siddharth Iyer, Debra Wu, Zongmin Zhao et al. "Cellular backpacks for macrophage immunotherapy." Science Advances 6, no. 18 (2020): eaaz6579. https://advances.sciencemag.org/content/6/18/eaaz6579?utm_source=yxnews&utm_medium=desktop&utm_referrer=https%3A%2F%2Fyandex.by%2Fnews

“Abstract: Adoptive cell transfers have emerged as a disruptive approach to treat disease in a manner that is more specific than using small-molecule drugs; however, unlike traditional drugs, cells are living entities that can alter their function in response to environmental cues. In the present study, we report an engineered particle referred to as a “backpack” that can robustly adhere to macrophage surfaces and regulate cellular phenotypes in vivo. Backpacks evade phagocytosis for several days and release cytokines to continuously guide the polarization of macrophages toward antitumor phenotypes. We demonstrate that these antitumor phenotypes are durable, even in the strongly immunosuppressive environment of a murine breast cancer model. Conserved phenotypes led to reduced metastatic burdens and slowed tumor growths compared with those of mice treated with an equal dose of macrophages with free cytokine. Overall, these studies highlight a new pathway to control and maintain phenotypes of adoptive cellular immunotherapies.”

PLGA from PolySciTech used in development of MRSA targeting nanoparticles for antibacterial applications.

Wednesday, May 13, 2020, 11:48 AM ET

Due to its resistance to most common antibiotics, Methicillin-resistant Staphylococcus aureus (MRSA) is an extremely difficult bacterial infection to treat. Recently, researchers at Temple University (Philadelphia, PA, USA) used PLGA (AP063) from PolySciTech (www.polyscitech.com) to create nanoparticles for attacking MRSA inside bone and biofilms. This research holds promise to provide for improved therapies against antibiotic resistant bacteria. Read more: Guo, Pengbo, Bettina A. Buttaro, Hui Yi Xue, Ngoc T. Tran, and Ho Lun Wong. "Lipid-polymer hybrid nanoparticles carrying linezolid improve treatment of methicillin-resistant Staphylococcus aureus (MRSA) harbored inside bone cells and biofilms." European Journal of Pharmaceutics and Biopharmaceutics (2020). https://www.sciencedirect.com/science/article/pii/S0939641120301041

“Methicillin-resistant Staphylococcus aureus (MRSA) is the most prevalent pathogen causing osteomyelitis. The tendency of MRSA to evade standard antibiotic treatment by hiding inside bone cells and biofilms is a major cause of frequent osteomyelitis recurrence. In this study, we developed a lipid-polymer hybrid nanoparticle loading the antibiotic linezolid (LIN-LPN), and focused on evaluating if this new nanoantibiotic can achieve significant in vitro activities against these intracellular and biofilm-embedded MRSA. The optimal LIN-LPN formulation demonstrated both high linezolid payload (12.0% by weight of nanoparticles) and controlled release characteristics (gradually released the entrapped antibiotic in 120 h). Although it achieved lower activities against bacteria including USA300-0114, CDC-587, RP-62A in planktonic form, it was substantially superior against the intracellular MRSA reservoir inside osteoblast cells. The differences of intracellular activities between LIN-LPN and linezolid were 87.0-fold, 12.3-fold, and 12.6-fold in CFU/ml (p < 0.05 or < 0.01) at 2 µg/ml, 4 µg/ml, and 8 µg/ml linezolid concentrations, respectively. LIN-LPN also suppressed the MRSA biofilm growth to 35–60% of the values achieved with free linezolid (p < 0.05). These enhanced intracellular and anti-biofilm activities of LIN-LPN were likely contributed by the extensive accumulation of LIN-LPN inside the MRSA-infected osteoblasts and biofilms as revealed in the confocal microscope images. The study thus validates the feasibility of exploiting the good nanoparticle-host cell and nanoparticle-biofilm interactions for improving the antibiotic drug activities against the poorly accessible bacteria, and supports LIN-LPN as a new alternative therapy for preventing the recurrence of MRSA-mediated bone infections. Keywords Osteomyelitis Nanoparticles Antibiotic Drug-resistant bacteria”

PLGA-PEG-NHS and mPEG-PLGA from PolySciTech used in development of targeted HIV therapy

Tuesday, May 12, 2020, 3:10 PM ET

HIV is a viral disease which attacks the immune system however targeted therapy can be applied to aid the immune system in fighting the virus which, along with anti-retroviral drugs, may present the potential to cure HIV. Recently, researchers at Creighton University used mPEG-PLGA (AK107) and PLGA-PEG-NHS (AI111) in development of anti-HIV nanoparticles. Read more: Mandal, Subhra, Shawnalyn W. Sunagawa, Pavan Kumar Prathipati, Michael Belshan, Annemarie Shibata, and Christopher J. Destache. "Targeted immuno-antiretroviral HIV therapeutic approach to provide dual protection and boosts cellular immunity: A proof-of-concept study." bioRxiv (2020). https://www.biorxiv.org/content/10.1101/2020.04.20.050849v1.abstract

“Human immunodeficiency virus (HIV)-infected active and latent CCR5 expressing long-lived T-cells are the primary barrier to HIV/AIDS eradication. Broadly neutralizing antibodies and latency-reversing agents are the two most promising strategies emerging to achieve ‘functional cure’ against HIV infection. Antiretrovirals (ARVs) have shown to suppress plasma viral loads to non-detectable levels and above strategies have demonstrated a ‘functional cure’ against HIV infection is achievable. Both the above strategies are effective at inducing direct or immune-mediated cell death of latent HIV+ T-cells but have shown respective limitations. In this study, we designed a novel targeted ARVs-loaded nanoformulation that combines the CCR5 monoclonal antibody and antiretroviral drugs (ARV) as a dual protection strategy to promote HIV ‘functional cure’. The modified CCR5 monoclonal antibody (xfR5 mAb) surface-coated dolutegravir (DTG) and tenofovir alafenamide (TAF) loaded nanoformulation (xfR5-D+T NPs) were uniformly sized

PLGA-thiol and Fol-PEG-COOH from PolyScitech used in nanoparticle cancer therapy

Tuesday, May 12, 2020, 3:10 PM ET

Cytochrome-c can be used to induce apoptosis (cell-death) in cancer cells. Recently, researchers at University of Puerto Rico, Universidad Central del Caribe, and Florida International University used PLGA-SH (AI025) and Folate-PEG-COOH (AE003) from PolySciTech (www.polyscitech.com) as part of their development of a cytochrome c delivery system for treatment of non-small cell lung cancer. Read more: Barcelo-Bovea, Vanessa, Irivette Dominguez-Martinez, Freisa Joaquin-Ovalle, Luis A. Amador, Elizabeth Castro-Rivera, Kristofer Medina-Alvarez, Anthony McGoron, Kai Griebenow, and Yancy Ferrer-Acosta. "Optimization and Characterization of Protein Nanoparticles for the Targeted and Smart Delivery of Cytochrome c to Non-Small Cell Lung Carcinoma." (2020). https://www.preprints.org/manuscript/202004.0221

“The delivery of Cytochrome c (Cyt c) to the cytosol stimulates apoptosis in cells were its release from mitochondria and apoptosis induction is inhibited. We developed a drug delivery system consisting of Cyt c nanoparticles decorated with folate-poly(ethylene glycol)-poly(lactic-co-glycolic acid)-thiol (FA-PEG-PLGA-SH) to deliver Cyt c into cancer cells and test their targeting in the Lewis Lung Carcinoma (LLC) mouse model. Cyt c-PLGA-PEG-FA nanoparticles (NPs) of 253 ± 55 and 354 ± 11 nm were obtained by Cyt c nanoprecipitation, followed by surface decoration with the co-polymer SH-PLGA-PEG-FA, and compared to a nanoparticle-free formulation. Overexpression of FA in LLC cells and internalization of Cyt c-PLGA-PEG-FA nanoparticles (NPs) was confirmed by confocal microscopy. Caspase activation assays show NPs retain 88-96% Cyt c activity. The NP formulations were more efficient in decreasing LLC cell viability than the NP-free formulation, with IC50: 49.2 to 70.1 μg/ml versus 129.5 μg/ml, respectively. Our NP system is thrice as selective towards cancerous than normal cells. In-vivo studies using tagged nanoparticles show accumulation in mouse LLC tumor 5 min post-injection. In conclusion, our NP delivery system for Cyt c shows superiority over the NP-free formulation and reaches a folic acid-overexpressing tumor in an immune-competent animal model.”

PLGA from PolySciTech used in study on drug delivery systems.

Tuesday, May 12, 2020, 3:09 PM ET

Understanding the mechanisitic properties which drive drug delivery systems is critical in designing long-acting injectable formulations. Recently, researchers at University of Connecticut, Qrono Inc, and FDA used PLGA (AP125) from PolySciTech (www.polyscitech.com) as part of their study into drug release mechanisms. Read more: Kohno, Moe, Janki V. Andhariya, Bo Wan, Sam Rothstein, Michael Hezel, Yan Wang, and Diane J. Burgess. "The Effect of PLGA Molecular Weight Differences on Risperidone Release from Microspheres." International Journal of Pharmaceutics (2020): 119339. (https://www.sciencedirect.com/science/article/pii/S0378517320303239)

“Abstract: The objective of the present study was to investigate the effect of molecular weight differences of poly (lactic-co-glycolic acid) (PLGA) on the in vitro release profile of risperidone microspheres. Four different PLGA molecular weights were investigated and all the microsphere formulations were prepared using the same manufacturing process. Physicochemical properties (particle size, drug loading, morphology and molecular weight) as well as in vitro degradation profiles of the prepared microspheres were investigated in addition to in vitro release testing. The in vitro release tests were performed using a previously developed flow through cell (USP apparatus 4) method. The particle size of the four prepared microsphere formulations varied, however there were no significant differences in the drug loading. Interestingly, the in vitro release profiles did not follow the molecular weight of the polymers used. Instead, the drug release appeared to be dependent on the glass transition temperature of the polymers as well as the porosity of the prepared formulations. The catalytic effect of risperidone (an amine drug) on PLGA during manufacturing and release testing, minimized the differences in the molecular weights of the four formulations, explaining the independence of the release profiles on PLGA molecular weight.”

PolySciTech Polymers used in development of novel anti-cancer therapy.

Tuesday, May 12, 2020, 3:08 PM ET

One solution to cancer therapy is to create a condition which starves the cancer so that it can not metabolize and grow. Recently, researchers at Chinese Academy of Sciences and Yangzhou university used polymers from PolySciTech (www.polyscitech.com) to create a nanoparticle therapy which acts to starve cancer. Read more: Wang, Huihui, Lu Cheng, Shang Ma, Liming Ding, Wei Zhang, Zhuobin Xu, Dandan Li, and Lizeng Gao. "Self-assembled multiple enzyme composites for enhanced synergistic cancer starving-catalytic therapy." ACS Applied Materials & Interfaces (2020). https://pubs.acs.org/doi/abs/10.1021/acsami.0c02006

“Abstract: Inspired by the particularity of tumor microenvironments, including acidity and sensibility to reactive oxygen species (ROS), advanced and smart responsive nanomaterials have recently been developed. The present study synthesized tumor-targeted and pH-sensitive supramolecular micelles that self-assembled via host–guest recognition. The micelles consumed intratumoral glucose and lactate via loading with glucose oxidase (GOD) and lactate oxidase (LOD). Intratumoral glucose and lactate were converted into hydrogen peroxide (H2O2) and were sequentially reduced to highly toxic hydroxyl radicals (▪OH) via the peroxidase (POD)-like activity of the loaded C-dot nanozymes. Tumor-killing effects were observed via cascade catalytic reactions. After intravenous injection, the nanocomposite exhibited an excellent tumor-targeted ability with good biocompatibility, which demonstrated its effective antitumor effect. The nanocomposite effectively combined starvation and catalytic therapy and exerted a synergistic anticancer effect with minimal side effects and without external addition.”

PLGA from PolySciTech used in development of donepezil-delivery system as treatment for Alzheimer’s disease

Monday, April 13, 2020, 9:59 AM ET

Donepezil is a drug often prescribed for treatment of Alzheimer’s disease however its oral administration in pill form is complicated by its gastric-irritation side effects and lack of patient compliance. For these reasons, a long-acting formulation would be preferable. Recently, researchers at Kangwon National University, Seoul National University (Korea), and UCLA used PLGA (AP059) as a donepezil-entrapment particle to be loaded into HA-Fe based hydrogel to provide for a long-lasting drug delivery system. This research holds promise to provide for improved therapies against Alzheimer’s disease. Read more: Lee, Song Yi, Ju-Hwan Park, Mingyu Yang, Min-Jun Baek, Min-Hwan Kim, Junmin Lee, Ali Khademhosseini, Dae-Duk Kim, and Hyun-Jong Cho. "Ferrous sulfate-directed dual-cross-linked hyaluronic acid hydrogels with long-term delivery of donepezil." International Journal of Pharmaceutics (2020): 119309. https://www.sciencedirect.com/science/article/pii/S0378517320302933

“Abstract: Ferrous sulfate (FeSO4)-directed dual-cross-linked hydrogels were designed for application in single-syringe injections. The use of FeSO4, rather than other iron salts, can modulate the gelation time and make it available for subcutaneous injection with a single syringe. These hydrogels are based on hyaluronic acid–dopamine (HA-dp) that contain donepezil (DPZ)-entrapping poly(lactic-co-glycolic acid) (PLGA) microsphere (MS). Although DPZ has been administered orally, its sustained release formulation via subcutaneous injection may reduce the dosing frequency for patients with Alzheimer’s disease. The HA-dp conjugate was synthesized via an amide bond reaction for coordination of dp with a metal ion (Fe2+ or Fe3+) and self-polymerization of dp. The HA-dp/DPZ-loaded PLGA MS (PD MS)/FeSO4 gel system was considerably hardened via both the coordination of the metal ion with HA-dp and covalent bonding of dp. In addition, a quick restoration of the collapsed gel structure and sustained DPZ release from the HA-dp/PD MS/FeSO4 structure were achieved. The pharmacokinetic parameters after its subcutaneous injection in a rat indicate the sustained release and absorption of DPZ from the HA-dp/PD MS/FeSO4 system. The proposed system can be prepared by a simple method and can be efficiently and safely used for the long-term delivery of DPZ after the subcutaneous injection.”

mPEG-PLGA from PolySciTech used in development of ketamine-delivery nanoparticles for reduced-addiction pain therapy

Monday, April 13, 2020, 9:58 AM ET

Typically, as a part of either post-surgical healing or chronic disease states (cancer, back damage, etc.) there is a need for long-lasting pain relief. Unfortunately, the opioid drugs which are conventionally used for this application have a highly addictive effect which has contributed greatly to society-wide opioid addiction issues. Recently, researchers at The University of Queensland (Australia) used mPEG-PLGA (AK026) from PolySciTech (www.polyscitech.com) to develop ketamine-delivery nanoparticles for reduced opioid pain treatment options that are less addictive. Read more: Han, Felicity Y., Yun Liu, Vinod Kumar, Weizhi Xu, Guangze Yang, Chun-Xia Zhao, Trent M. Woodruff, Andrew K. Whittaker, and Maree T. Smith. "Sustained-release ketamine-loaded nanoparticles fabricated by sequential nanoprecipitation." International Journal of Pharmaceutics (2020): 119291. https://www.sciencedirect.com/science/article/pii/S0378517320302751

“Abstract: Ketamine in sub-anaesthetic doses is an analgesic adjuvant with a morphine-sparing effect. Co-administration of a strong opioid with an analgesic adjuvant such as ketamine is a potential treatment option, especially for patients with cancer-related pain. A limitation of ketamine is its short in vivo elimination half-life. Hence, our aim was to develop biocompatible and biodegradable ketamine-loaded poly(ethylene glycol) (PEG)-block-poly(lactic-co-glycolic acid) (PLGA) nanoparticles for sustained release. Ketamine-encapsulated single polymer PEG-PLGA nanoparticles and double polymer PEG-PLGA/shellac (SH) nanoparticles with a high drug loading of 41.8% (drug weight/the total weight of drug-loaded nanoparticles) were prepared using a new sequential nanoprecipitation method. These drug-loaded nanoparticles exhibited a sustained-release profile for up to 21 days in vitro and for more than 5 days after intravenous injection in mice. Our study demonstrates that high drug loading and a sustained release profile can be achieved with ketamine-loaded PEG-PLGA nanoparticles prepared using this new nanoprecipitation method.”

PEG-PCL from PolySciTech used in polymersome drug delivery development.

Saturday, April 11, 2020, 10:52 AM ET

Providing for drug encapsulation greatly improves stability and delivery of therapeutic molecules. Recently, researchers at Ruprecht-Karls-University (Germany) used PEG-PCL (AK128) from PolySciTech (www.polyscitech.com) to create a polymersome system for delivery of model hydrophobic and peptide-based drugs. This research holds promise for improved drug-delivery systems in the future. Read more: Köthe, Tobias, Stefan Martin, Gabriele Reich, and Gert Fricker. "Dual asymmetric centrifugation as a novel method to prepare highly concentrated dispersions of PEG-b-PCL polymersomes as drug carriers." International Journal of Pharmaceutics (2020): 119087. https://www.sciencedirect.com/science/article/pii/S0378517320300715

“Abstract: Polymersomes are vesicles formed by self-assembly from block copolymers. A widely studied biodegradable diblock copolymer that forms polymersomes is poly(ethylene-glycol)-block-poly(ε-caprolactone) (PEG-b-PCL). Polymersomes from this copolymer have been prepared by various methods. Major drawbacks are either the use of organic solvents, the need for post-preparation steps or low polymer concentration in resulting dispersions. Here, we studied the use of dual asymmetric centrifugation (DAC) as alternative and innovative preparation method by which these disadvantages can be overcome. We investigated the influence of process parameters on the size of resulting particles and their morphology. Additionally, the ability of this method to encapsulate both hydrophilic and hydrophobic drugs into polymersomes was assessed to evaluate its usefulness in the manufacture of nano-therapeutics. We found, that depending on process parameters, formation of nanosized vesicles with considerable drug encapsulation is achievable. Interestingly, with DAC polymersomes could also be prepared from a high molecular weight copolymer that was not able to generate vesicles by conventional methods. In addition, no organic solvents are used, no postprocessing is necessary and preparation is done quickly in a single vessel, minimizing product loss. DAC leads to highly concentrated, drug-loaded polymersome dispersions and therefore represents a major step towards their applicability in nanomedicine.”

PEG-PLA from PolySciTech used in development of nanoparticle-based therapy of Lou Gehrig's disease

Wednesday, April 8, 2020, 9:21 AM ET

Lou Gehrig’s disease, or ALS (amyotrophic lateral sclerosis) is a fatal and progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Recently, researchers at Barrow Neurological Institute and University of Texas used PEG-PLA (AK054) and PLGA (AP037) from PolySciTech (www.polyscitech.com) to create adapalene loaded nanoparticles for ALS treatment. This research holds promise for treating this fatal disease. Read more: Medina, David X., Eugene P. Chung, Collin D. Teague, Robert Bowser, and Rachael W. Sirianni. "Intravenously Administered, Retinoid Activating Nanoparticles Increase Lifespan and Reduce Neurodegeneration in the SOD1G93A Mouse Model of ALS." Frontiers in Bioengineering and Biotechnology 8 (2020): 224. https://www.frontiersin.org/articles/10.3389/fbioe.2020.00224/full

“Dysregulation of the retinoic acid (RA) signaling pathway is observed in amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Here, we investigated the therapeutic potential of retinoid activation via the RA receptor β (RARβ) in the SOD1G93A mouse model of ALS. Our approach utilized the RARβ agonist adapalene, which we previously found to be neuroprotective in vitro. Adapalene, like most retinoids, is poorly water soluble, which has thus far prevented effective drug delivery in vivo. To address this challenge, we encapsulated adapalene within nanoparticles (Adap-NPs) composed of poly(lactic acid)-poly(ethylene glycol) (PLA-PEG). Our data demonstrate that intravenous administration of Adap-NPs robustly activates retinoid signaling in the CNS. Chronic administration of Adap-NPs resulted in improved motor performance, prolonged lifespan, and neuroprotection in SOD1G93A mice. This study highlights retinoid signaling as a valuable therapeutic approach and presents a novel nanoparticle platform for the treatment of ALS.”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.5613009929657 seconds)


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