Co-Delivery of Paclitaxel and Α-Tocopherol Succinate by Novel Chitosan-Based Polymeric Micelles for Improving Micellar Stability and Efficacious Combination Therapy Publisher Pubmed



Emami J¹ ; Rezazadeh M¹ ; Rostami M² ; Hassanzadeh F² ; Sadeghi H³ ; Mostafavi A¹ ; Minaiyan M⁴ ; Lavasanifar A⁵ Show Affiliations
Source: Drug Development and Industrial Pharmacy Published:2015

Abstract

The aim of this study was to develop chitosan derivative polymeric micelles for co-delivery of paclitaxel (PTX) and α-tocopherol succinate (α-TS) to the cancer cells to improve the therapeutic efficiency and reduce side effects of PTX. In this study, amphiphilic tocopheryl succinate-grafted chitosan oligosaccharide was synthesized and physically loaded by PTX and α-TS with entrapment efficiency of 67.9% and 73.2%, respectively. Physical incorporation of α-TS into the micelles increased the hydrophobic interaction between PTX and the micelles core, which improved micelle stability, reduced the micelle size and also sustained the PTX release from the micelles. The mean particle size and zeta potential of αTS/PTX-loaded micelles were about 133 nm and 25.2 mV, respectively, and PTX release was completed during 6-9 d from the micelles. Furthermore, the cytotoxicity of α-TS/PTX-loaded micelles against human ovarian cancer cell line cancer cell in vitro was higher than that of PTX-loaded micelles and the free drug solution. Half maximal inhibitory concentration values of PTX after 48-h exposure of the cells to the PTX-loaded micelles modified and unmodified with α-TS were 110 and 188 ng/ml, respectively. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.