Tuesday, June 30, 2020

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

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”

Friday, June 26, 2020

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

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.”

Monday, June 22, 2020

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

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.”

Wednesday, June 10, 2020

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

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

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

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”

Tuesday, June 2, 2020

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

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 (