Development and evaluation of long-circulating nanoparticles loaded with betulinic acid for improved anti-tumor efficacy

Publication date: 5 October 2017 Source:International Journal of Pharmaceutics, Volume 531, Issue 1 Author(s): Ankit Saneja, Robin Kumar, Amarinder Singh, Ravindra Dhar Dubey, Mubashir J. Mintoo, Gurdarshan Singh, Dilip M. Mondhe, Amulya K. Panda, Prem N. Gupta The clinical application of betulinic acid (BA), a natural pentacyclic triterpenoid with promising antitumor activity, is hampered due to its extremely poor water solubility and relatively short half-life in the systemic circulation. In order to address these issues, herein, we developed betulinic acid loaded polylactide-co-glycolide- monomethoxy polyethylene glycol nanoparticles (PLGA-mPEG NPs). The PLGA-mPEG co-polymer was synthesized and characterized using NMR and FT-IR. BA loaded PLGA-mPEG NPs were prepared by an emulsion solvent evaporation method. The developed nanoparticles had a desirable particle size (∼147nm) and exhibited uniform spherical shape under transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The PLGA-mPEG NPs were able to decrease the uptake by macrophages (i.e. J774A.1 and Raw 264.7 cells) as compared to PLGA nanoparticles. In vitro cytotoxicity in MCF7 and PANC-1 cells demonstrated enhanced cytotoxicity of BA loaded PLGA-mPEG NPs as compared to free BA. The cellular uptake study in both the cell lines demonstrated time dependent uptake behavior. The enhanced cytotoxicity of BA NPs was also supported by increased cellular apoptosis, mitochondrial membrane ...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research