The Entrapment of Paclitaxel in PLGA Nanoparticles Increases its Cytotoxicity against Multiresistant Cell Line
Vanya Bojat *
Department of Pharmacology of Pharmaceutical Faculty, I.M. Sechenov First Moscow State Medical University (MSMU), Moscow, Russia.
Vadim Balabanyan
Department of Pharmacology of Pharmaceutical Faculty, I.M. Sechenov First Moscow State Medical University (MSMU), Moscow, Russia.
Renad Alyautdin
Department of Pharmacology of Pharmaceutical Faculty, I.M. Sechenov First Moscow State Medical University (MSMU), Moscow, Russia.
*Author to whom correspondence should be addressed.
Abstract
Paclitaxel (Ptx) is a taxane anticancer mitotic inhibitor, widely used in oncology for the last 20 years. Poor solubility of Ptx, as a consequence using of toxic solvents such as Cremofor EL, high affinity to P-glycoprotein are associated with serious side effects due to hypersensitivity reactions, low bioavailability and low therapeutic index. Development of new delivery solvent-free forms of Ptx is one of the key research problems in modern cancer chemotherapy.
Ptx loaded into polylactic-co-glycolic acid (PLGA) nanoparticles (Ptx-PLGA-Nps) (size 200-300 nm) have been prepared using nanoprecipitation method. Impact of technological parameters on Ptx encapsulation efficacy and in vitro drug release was investigated. Drug encapsulation was determined using HPLC. Citotoxic activity and cell accumulation of nanosomal formulation of Ptx was studied on multiresistant cell line Jurkat WT (cells of human Т-limphoblastic leucosis). Obtained results suggest that formulation of PLGA Ptx nanoparticles have above 90-98% drug encapsulation efficacy, higher cell accumulation and cytotoxic activity.
Keywords: Paclitaxel, nanoparticles, multiresistance, P-glycoprotein