Monday, March 14, 2016

PEG-PLGA nanoparticles investigated for delivery of orlistat and antisense miRNA for triple-negative breast cancer therapy

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable research polymers including PEG-PLGA block copolymers for drug-delivery applications. Recently, these types of polymers were used to generate nanoparticles loaded with Orlistat along with doxorubicin or antisense-miR-21. Orlistat is traditionally used to treat obesity, as it acts as a gastric lipase inhibitor. However, it also inhibits the thioesterase domain of fatty acid synthase, which is an enzyme involved in cancer cell proliferation. When this drug was delivered via nanoparticles it more effectively inhibited growth of breast-cancer cells than when delivered as loose drug. When it was co-delivered in a PEG-PLGA nanoparticle formulation along with conventional chemotherapeutic doxorubicin or antisense miR-21, an inhibitor of microRNA-21 which is a cancer-related RNA sequence that affects cancer migration, apoptosis, and growth, the combined drugs had a powerful synergistic effect against cancer proliferation. Read more: Bhargava-Shah, Aarohi, Kira Foygel, Rammohan Devulapally, and Ramasamy Paulmurugan. "Orlistat and antisense-miRNA-loaded PLGA-PEG nanoparticles for enhanced triple negative breast cancer therapy." Nanomedicine 0 (2016). http://www.futuremedicine.com/doi/abs/10.2217/nnm.15.193

“Abstract: Background: This study explores the use of hydrophilic poly(ethylene glycol)-conjugated poly(lactic-co-glycolic acid) nanoparticles (PLGA-PEG-NPs) as delivery system to improve the antitumor effect of antiobesity drug orlistat for triple-negative breast cancer (TNBC) therapy by improving its bioavailability. Materials & methods: PLGA-PEG-NPs were synthesized by emulsion-diffusion-evaporation method, and the experiments were conducted in vitro in MDA-MB-231 and SKBr3 TNBC and normal breast fibroblast cells. Results: Delivery of orlistat via PLGA-PEG-NPs reduced its IC50 compared with free orlistat. Combined treatment of orlistat-loaded NPs and doxorubicin or antisense-miR-21-loaded NPs significantly enhanced apoptotic effect compared with independent doxorubicin, anti-miR-21-loaded NPs, orlistat-loaded NPs or free orlistat treatments. Conclusion: We demonstrate that orlistat in combination with antisense-miR-21 or current chemotherapy holds great promise as a novel and versatile treatment agent for TNBC.”
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