Biodegradable nano-architectural PEGylated approach for the improved stability and anticancer efficacy of bendamustine

Bendamustine is a drug of choice for the treatment of several cancers including non- Hodgkin lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL). The unstable nature of the drug, however, offers a major obstacle in its effective formulation development. The present study was aimed to achieve improved stability and efficacy of bendamustine via co-polymeric PEG-PLGA nanoparticulate approach. PEG-PLGA co-polymeric conjugate was synthesized and characterized by FT-IR and H-1 NMR spectroscopy. Bendamustine loaded nanoparticles (PLGA and PEG-PLGA) were prepared, optimized and characterized for size, zeta and electron microscopy (SEM and TEM). The average size, pdi (polydispersity index), zeta potential and entrapment efficiency for bendamustine loaded PEG-PLGA nanoparticles (PPBNP 15) was 297.3 +/- 2.055 nm, 0.256 +/- 0.012, -6.62 +/- 0.081 mV and 52.30 +/- 3.66%, respectively. The in vitro release studies displayed sustained release nature of bendamustine. The Krosmeyer-Peppas model was the best fit model as a result of kinetic modelling for in vitro release. The ex vivo hemolytic toxicity of the PPBNP 15 was significantly less (approx. 11%; 4 folds) compared to pure drug (p <0.05). The cytotoxicity study showed significantly higher anticancer activity against MCF-7, T47D and PC-3 cells (p < 0.05) compared to naive bendamustine. The developed biodegradable nanoparticles improved the stability of bendamustine and were equally stable, less toxic and highly effective against different cancerous cells. (C) 2016 Elsevier B.V. All rights reserved.