Monday, November 19, 2018

mPEG-PLGA and PLGA from PolySciTech used in development of nanoparticle combination therapy for brain-cancer treatment


Glioblastoma is a form of brain-cancer that is highly aggressive with a 15-16 month median patient survival rate. Use of nanoparticles which may cross the blood-brain-barrier, along with combination therapeutic approaches, may provide further treatment options. Recently, researchers at University of Massachusetts Lowell used mPEG-PLGA (PolyVivo AK037) and PLGA (AP041) from PolySciTech (www.polyscitech.com) to create nanoparticles loaded with a combination of photosensitizers and chemotherapy agents for treatment against this disease. This research holds promise to provide for improved therapeutic options against this fatal disease. Read more: Kydd, Janel, Rahul Jadia, and Prakash Rai. "Co-Administered Polymeric Nano-Antidotes for Improved Photo-Triggered Response in Glioblastoma." Pharmaceutics 10, no. 4 (2018): 226. https://www.mdpi.com/1999-4923/10/4/226/htm

“Abstract: Polymer-based nanoparticles (NPs) are useful vehicles in treating glioblastoma because of their favorable characteristics such as small size and ability to cross the blood–brain barrier, as well as reduced immunogenicity and side effects. The use of a photosensitizer drug such as Verteporfin (BPD), in combination with a pan-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), Cediranib (CED), encapsulated in NPs will provide the medical field with new research on the possible ways to treat glioblastoma. Concomitant administration of BPD and CED NPs have the potential to induce dual photocytotoxic and cytostatic effects in U87 MG cells by (1) remotely triggering BPD through photodynamic therapy by irradiating laser at 690 nm and subsequent production of reactive oxygen species and (2) inhibiting cell proliferation by VEGFR interference and growth factor signaling mechanisms which may allow for longer progression free survival in patients and fewer systemic side effects. The specific aims of this research were to synthesize, characterize and assess cell viability and drug interactions for polyethylene-glycolated (PEGylated) polymeric based CED and BPD NPs which were less than 100 nm in size for enhanced permeation and retention effects. Synergistic effects were found using the co-administered therapies compared to the individual drugs. The major goal of this research was to investigate a new combination of photodynamic-chemotherapy drugs in nano-formulation for increased efficacy in glioblastoma treatment at reduced concentrations of therapeutics for enhanced drug delivery in vitro. Keywords: drug delivery; cancer; polymer; nanomedicine; angiogenesis; blood–brain barrier”

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Wednesday, November 14, 2018

Block-copolymers from PolySciTech used in the development of nano-emulsion based ultra-sound mediated noninvasive targeted drug delivery

Due to the circulatory nature of the human bloodstream, any agent introduced into the bloodstream at any location is quickly spread throughout the human body. This is good for drugs which need to be spread throughout the human body (i.e. systemic dosage) however is not very efficient for drugs whose location of action is only in one particular region. Researchers at Stanford University and Massachusetts General Hospital used several PEG-PCL, PEG-PLA, PEG-PLGA copolymers (Polyvivo AK073, AK001, AK052, AK090, AK004, and AK003) from PolySciTech (www.polyscitech.com) to generate nanoparticles with perfluorocarbons that could be activated using ultrasound. In this way the drug can be administered systemically but then released (uncaged) in the desired location of action. This research holds promise to enable targeted drug delivery with minimal side-effects. Read more: Zhong, Qian, Byung C. Yoon, Muna R. Aryal, Jeffrey B. Wang, Ananya Karthik, and Raag D. Airan. "Polymeric perfluorocarbon nanoemulsions are ultrasound-activated wireless drug infusion catheters." bioRxiv (2018): 315044. https://www.biorxiv.org/content/early/2018/09/10/315044.short

“Abstract: Catheter-based intra-arterial drug therapies have proven effective for a range of oncologic, neurologic, and cardiovascular applications. However, these procedures are limited by their invasiveness, as well as the relatively broad drug spatial distribution that is achievable with selective arterial catheterization. The ideal technique for local pharmacotherapy would be noninvasive and would flexibly deliver a given drug to any region of the body. Combining polymeric perfluorocarbon nanoemulsions with existent clinical focused ultrasound systems could in principle enable noninvasive targeted drug delivery, but it has not been clear whether these nanoparticles could provide the necessary drug loading, stability, and generalizability across a range of drugs to meet these needs, beyond a few niche applications. Here, we directly address all of those challenges and fully develop polymeric perfluorocarbon nanoemulsions into a generalized platform for ultrasound-targeted drug delivery with high potential for clinical translation. We demonstrate that a wide variety of drugs may be effectively uncaged with ultrasound using these nanoparticles, with drug loading increasing with hydrophobicity. We also set the stage for clinical translation by delineating production protocols that hew to clinical standards and yield stable and optimized ultrasound-activated drug-loaded nanoemulsions. Finally, as a new potential clinical application for these nanoemulsions, we exhibit their in vivo efficacy and performance for cardiovascular applications, by achieving local vasodilation in the highest flow vessel of the body, the aorta. This work establishes the power of polymeric perfluorocarbon nanoemulsions as a clinically-translatable platform for effective noninvasive ultrasonic drug uncaging for myriad targets in the brain and body.”

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PLGA from PolySciTech used in development of mixing system for rapid generation of nanoparticles

Nanoparticles are generally created by a controlled nanoprecipitation of polymer into a non-solvent. There are many different ways to generate nanoparticles which fundamentally differ mostly on how the mixing of polymer solution and non-solvent is accomplished. Recently, researchers at San Jose State University used PLGA (multiple types) from PolySciTech (www.polyscitech.com) to generate nanoparticles by a rapid and inexpensive technique using a 3D printed mixer. This research holds promise to enable rapid and simple creation of PLGA nanoparticles in a cost-effective manner. Read more: Le, Lan, Anuja Bokare, and Folarin Erogbogbo. "Hand Powered, cost effective, 3D printed nanoparticle synthesizer: Effects of polymer end caps, drugs, and solvents on lipid polymer hybrid nanoparticles." Materials Research Express (2018). http://iopscience.iop.org/article/10.1088/2053-1591/aaed72/meta

“Abstract: Lipid polymer hybrid nanoparticles (LPHNPs) consisting PLGA polymer as a core and DSPE-PEG as a lipid shell have been synthesized by nanoprecipitation method using hand powered, 3D printed Multi Inlet Vortex Mixer (MIVM). This method is relatively fast, simple and cost-effective as compared to other methods used for the synthesis of LPHNPs. Considering the importance of particle size in the nanoparticle mediated drug delivery, synthesis of LPHNPs with desired size has been attempted by examining various formulation variables. The synthesis conditions such as PLGA end caps, amount of drug and the type of organic solvent have been optimized to obtain LPHNPs of desired size. The formation of core-shell like structure of LPHNPs is confirmed by TEM analysis. The resulting LPHNPs were proven to have long term stability and controlled drug release properties.”

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PLGA from PolySciTech used in developing DP44mt loaded nanoparticles for cancer therapy against resistant cancers


DP44mt is a chelator molecule that binds iron and removes it from the intracellular environment. In cancer cells, this agent acts to induce cancer-cell death through upregulation of AMPK pathway and through corrupting autophagic mechanisms. One of the benefits of this therapeutic molecule is that it works against strains of cancers which are resistant to conventional chemotherapy. Recently, researchers at University of Houston purchase PLGA (AP041) from PolySciTech (www.polyscitech.com) for use in developing nanoparticles loaded with DP44mt. This research holds promise to provide for improved therapies against chemoresistant tumors. Read more: Holley, C. K., S. Alkhalifah, and S. Majd. "Fabrication and Optimization of Dp44mT-Loaded Nanoparticles." In 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), pp. 5733-5736. IEEE, 2018. https://ieeexplore.ieee.org/abstract/document/8513598/

“This paper describes the modulation of polymeric nanoparticle (NP) preparation to produce an optimal nanocarrier for delivery of the potent anti-tumor iron chelator, Di2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) towards application in cancer therapy. We have previously shown the potential of poly (lactic-co-glycolic acid) (PLGA) NPs as a nano-carrier for delivery of Dp44mT to malignant cells. The focus of this study is to alter the fabrication parameters to improve the characteristics of these NPs as a delivery vehicle for Dp44mT. To this end, PLGA NPs encapsulating Dp44mT are fabricated using the nanoprecipitation method with systematic variations in (i) the amount of surfactant poly (vinyl alcohol) (PVA) in aqueous phase, and (ii) the drug to polymer ratio in organic phase. The resultant NPs are characterized for size, surface potential, encapsulation efficiency, and drug release profile. Results of this study showed that increasing the PVA % (within the examined range of 0.5-4% w/v) and decreasing the Dp44mT to PLGA ratio (within the tested range of 0.0375-0.3: 1 mg/mL) both led to an increase in drug encapsulation efficiency. Focusing on the optimal PVA percentage, we found that the changes in drug to polymer ratio did not have a significant impact on the size distribution and surface potential of Dp44mT-NPs and these NPs remained in the desirable range of 80-120 nm. Lastly, the release of Dp44mT from NPs differed for different Dp44mT: PLGA ratios, providing a means to further optimize the NP formulation for future cancer treatment applications. Keywords: Drugs, Encapsulation, Polymers, Cancer, Fabrication, Nanoparticles, Iron”

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Thursday, November 8, 2018

Get ‘Bezwa-more’ for your Bezwada-branded product purchase placed through PolySciTech with discount code BEZWADA40



In addition to in-house manufactured materials, PolySciTech also carries products by high-quality suppliers with a focus on biomedical and polymer products. Starting from November 8 through December 31, receive an additional 40% discount off the price of Bezwada-Brand products purchased through PolySciTech using the coupon code BEZWADA40. This includes the APB*** series of high molecular weight specialty polyesters for mechanically-demanding applications. Includes polymers of glycolide, caprolactone, dioxanone, lactide, trimethylene carbonate and other monomers with focus on mechanically robust products for implants, sutures, and other applications where strength and elasticity are paramount. Also included are the AEB*** series of Poly(ethylene glycol)-diacrylates are the ideal, cross-linkable hydrogel precursor for use in micropatterning, cell-scaffolds, and biological functions. Simply mixing these polymers with an appropriate solution of commercially available and biocompatible photo-initiator generates a liquid solution which readily forms into a solid gel upon exposure to UV light. Find these products with a competitive discount at www.polyscitech.com.

Tuesday, November 6, 2018

mPEG-PLA and PLA-PEG-COOH from PolySciTech used in the development of nanoparticles to treat colon cancer


Galbanic acid is a naturally occurring compound extracted from Ferula (wild carrots) which has potent activity against cancer, as well as anticoagulative, antiviral, and antibacterial properties. Despite its promising biological activity, it has very poor water solubility, which limits its clinical usefulness. Recently, researchers at Mashhad University of Medical Sciences (Iran) used mPEG-PLA (Cat# AK054) and PLA-PEG-COOH (Cat# AI030) from PolySciTech (www.polyscitech.com) to create galbanic-acid loaded nanoparticles. They assayed these particles against colorectal cancer and found promising results for efficacy against this form of cancer. This research holds promise for improved therapy against cancer with lower side-effects. Read more: Afsharzadeh, Maryam, Khalil Abnous, Rezvan Yazdian–Robati, Armin Ataranzadeh, Mohammad Ramezani, and Maryam Hashemi. "Formulation and evaluation of anticancer and antiangiogenesis efficiency of PLA–PEG nanoparticles loaded with galbanic acid in C26 colon carcinoma, in vitro and in vivo." Journal of cellular physiology (2018). https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.27346

“Abstract: Galbanic acid (GBA) is an active sesquiterpene coumarin derivative, with various medicinal benefits, including anticancer properties. However, the low solubility of GBA is the main limitation of its clinical applications. In this study, we used a nanosystem based on poly (D, l‐lactide)–polyethylene glycol (PLA–PEG), for the delivery of GBA to C26 colon carcinoma cells. The physicochemical characteristics of nanoparticles (NPs) prepared by the emulsification–evaporation method were evaluated. MTT assay was used to compare the anticell proliferation of GBA and PLA–PEG–GBA against C26 cell lines. PLA–PEG‐NPs with an average size of about 140 nm had an enhanced release of GBA at a pH of 5.5 compared with a pH of 7.4. Cytotoxicity studies showed that the IC 50 of the PLA–PEG–GBA NPs (8 µM) was significantly lower than free GBA (15 µM). In the in vivo study, PLA–PEG–GBA NPs exhibited remarkable efficacy and reduced in vivo toxicity in C26 colon carcinoma tumor‐bearing female BALB/c mice. To study the antiangiogenesis effect of the NPs, tumor sections were stained with an anti CD34 antibody. The results show the CD34 (+) vessels were decreased in the GBA and PLA–PEG–GBA treated mice by more than 75% and 90%, respectively. These results suggest that the encapsulation of GBA into the PLA–PEG could potentially be used for the treatment of colorectal cancer.”

Tuesday, October 30, 2018

PLGA from PolySciTech used in development of nanoparticle therapy against non-small cell lung cancer

Non-small cell lung cancer is an extremely common form of cancer, leading to more than 200,000 cases in USA per year. This type of cancer typically responds poorly to chemotherapy and often becomes resistant against many chemotherapeutics. Recently, researchers at Keck Graduate Institute, St. John's University, University of La Verne, and Harvard University used PLGA (PolyVivo AP082) from PolySciTech (www.polyscitech.com) to develop erlotinib loaded nanoparticles and tested these as a means to bypass NSCLC chemotherapy resistance. This research holds promise to provide for more effective treatments against this form of cancer. Read more: Vaidya, Bhuvaneshwar, Vineela Parvathaneni, Nishant S. Kulkarni, Snehal K. Shukla, Jenna K. Damon, Apoorva Sarode, Dipti Kanabar et al. "Cyclodextrin modified erlotinib loaded PLGA nanoparticles for improved therapeutic efficacy against non-small cell lung cancer." International Journal of Biological Macromolecules (2018). https://www.sciencedirect.com/science/article/pii/S0141813018338972

“Abstract: This study was aimed at developing a nanoparticle strategy to overcome acquired resistance against erlotinib in non-small cell lung cancer (NSCLC). To load erlotinib on biodegradable PLGA nanoparticles, erlotinib-cyclodextrin (Erlo-CD) complex was prepared using β-cyclodextrin sulfobutyl ether, which was in turn loaded in the core of PLGA nanoparticles using multiple emulsion solvent evaporation. Nanoparticles were characterized for size distribution, entrapment and loading efficiency, in-vitro release, and therapeutic efficacy against different lung cancer cells. Effect of formulation on cell cycle, apoptosis, and other markers was evaluated using flow cytometry and western blotting studies. The efficacy of optimized nanoformulation was evaluated using a clinically relevant in-vitro 3D-spheroid model. Results showed that Erlo-CD loaded nanoparticles (210 ± 8 nm in size) demonstrated 3-fold higher entrapment (61.5 ± 3.2% vs 21.9 ± 3.7% of plain erlotinib loaded nanoparticles) with ~5% loading efficiency and sustained release characteristics. Developed nanoparticles demonstrated significantly improved therapeutic efficacy against NSCLC cells in terms of low IC50 values and suppressed colony forming ability of cancer cells, increased apoptosis, and autophagy inhibition. Interestingly, 3D spheroid study demonstrated better anticancer activity of Erlo-CD nanoparticles compared to plain erlotinib. Present study has shown a premise to improve therapeutic efficacy against erlotinib-resistant lung cancer using modified nanoErlo formulations. Keywords: Erlotinib Sulfobutylether β-cyclodextrin complex Resistance lung cancer Autophagy 3D spheroids”