Design and characterization of paclitaxel-verapamil co-encapsulated PLGA nanoparticles: Potential system for overcoming P-glycoprotein mediated MDR

Paclitaxel (PTX) is one of the most effective drugs for treating a variety of solid tumors. Due to its poor aqueous solubility, Cremophor EL is used as solvent for its marketed formulation which may cause severe side effects in patients. Another problem in PTX delivery is over expression of P-glycoprotein which contributes to the development of multidrug resistance in cancer cells. Considering Verapamil (VER) calcium channels and P-gp pumps inhibiting effects, it seems co-administration of PTX and VER may increase accumulation of PTX inside cancer cells. Polymeric nanoparticles seem to be one of the best carriers for PTX in order to eliminate Cremophor EL in addition to co-encapsulating ability. The aim of this study is to develop and optimize PLGA nanoparticles for co-encapsulation of PTX and VER.Coencapsulated PLGA nanoparticles were evaluated for particles size, zeta potential (ZP), drug loading%, encapsulation efficiency% and in vitro release of drugs. Cell cytotoxicity studies were also performed on MCF-7 cell line. PLGA NPs with 470 nm diameter with acceptable PTX and VER loading and release% presented higher cytotoxicity in some concentrations compared with free-PTX after 72 h. Results suggesting PLGA NPs may potentially be useful drug carrier for co-encapsulation of PTX and VER.

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