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BioMed Research International
Volume 2013 (2013), Article ID 712678, 18 pages
http://dx.doi.org/10.1155/2013/712678
Research Article

Formulation Development and Evaluation of Hybrid Nanocarrier for Cancer Therapy: Taguchi Orthogonal Array Based Design

Department of Pharmaceutical Science, College of Pharmacy, University of Hawaii at Hilo, 34 Rainbow Drive, Suite 300 Hilo, HI 96720, USA

Received 1 May 2013; Accepted 13 June 2013

Academic Editor: René Holm

Copyright © 2013 Rakesh K. Tekade and Mahavir B. Chougule. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Taguchi orthogonal array design is a statistical approach that helps to overcome limitations associated with time consuming full factorial experimental design. In this study, the Taguchi orthogonal array design was applied to establish the optimum conditions for bovine serum albumin (BSA) nanocarrier (ANC) preparation. Taguchi method with L9 type of robust orthogonal array design was adopted to optimize the experimental conditions. Three key dependent factors namely, BSA concentration (% w/v), volume of BSA solution to total ethanol ratio (v : v), and concentration of diluted ethanolic aqueous solution (% v/v), were studied at three levels 3%, 4%, and 5% w/v; 1 : 0.75, 1 : 0.90, and 1 : 1.05 v/v; 40%, 70%, and 100% v/v, respectively. The ethanolic aqueous solution was used to impart less harsh condition for desolvation and attain controlled nanoparticle formation. The interaction plot studies inferred the ethanolic aqueous solution concentration to be the most influential parameter that affects the particle size of nanoformulation. This method (BSA, 4% w/v; volume of BSA solution to total ethanol ratio, 1 : 0.90 v/v; concentration of diluted ethanolic solution, 70% v/v) was able to successfully develop Gemcitabine (G) loaded modified albumin nanocarrier (M-ANC-G) of size  nm (  mV) as against to  nm (  mV) using conventional method albumin nanocarrier (C-ANC-G). Hybrid nanocarriers were generated by chitosan layering (solvent gelation technique) of respective ANC to form C-HNC-G and M-HNC-G of sizes nm (  mV) and  nm (  mV), respectively. Zeta potential, entrapment, in vitro release, and pH-based stability studies were investigated and influence of formulation parameters are discussed. Cell-line-based cytotoxicity assay (A549 and H460 cells) and cell internalization assay (H460 cell line) were performed to assess the influence on the bioperformance of these nanoformulations.