Friday, August 21, 2015

PLGA from PolySciTech used in developing metronomic delivery of PTX to treat ovarian cancer

PolySciTech (www.polyscitech.com) provides a wide array of PLGA and related products. PLGA degradation speed depends on lactide:glycolide ratio as well as molecular weight. PLGA’s with lower lactide ratios, down to 50%, and lower molecular weights tend to degrade faster as water easily gains access to the relatively short polymer chain and cleaves it into little pieces. Recently one of Akina’s fastest degrading polymers AP037 (PLGA 50:50 Mn 1000-5000) was combined with a very slow degrading PLGA with high molecular weight to create a nanoparticle which had controlled release properties of paclitaxel. This system was found to be less susceptible to cells developing resistance as there was less drug-free time periods in between doses. Read more: Amoozgar, Zohreh, Lei Wang, Tania Brandstoetter, Samuel S. Wallis, Erin M. Wilson, and Michael S. Goldberg. "Dual-layer surface coating of PLGA-based nanoparticles provides slow-release drug delivery to achieve metronomic therapy in a paclitaxel-resistant murine ovarian cancer model." Biomacromolecules 15, no. 11 (2014): 4187-4194. http://pubs.acs.org/doi/abs/10.1021/bm5011933

“Abstact: Development of drug resistance is a central challenge to the treatment of ovarian cancer. Metronomic chemotherapy decreases the extent of drug-free periods, thereby hindering development of drug resistance. Intraperitoneal chemotherapy allows for treatment of tumors confined within the peritoneum, but achieving sustained tumor-localized chemotherapy remains difficult. We hypothesized that modulating the surface properties of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles could enhance their drug retention ability and extend their release profile, thereby enabling metronomic, localized chemotherapy in vivo. Paclitaxel was encapsulated in particles coated with a layer of polydopamine and a subsequent layer of poly(ethylene glycol) (PEG). These particles achieved a 3.8-fold higher loading content compared to that of nanoparticles formulated from linear PLGA–PEG copolymers. In vitro release kinetic studies and in vivo drug distribution profiles demonstrate sustained release of paclitaxel. Although free drug conferred no survival advantage, low-dose intraperitoneal administration of paclitaxel-laden surface-coated nanoparticles to drug-resistant ovarian tumor-bearing mice resulted in significant survival benefits in the absence of any apparent systemic toxicity”


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