Screening the Most Effective Variables on Physical Properties of Folate-Targeted Dextran/Retinoic Acid Micelles by Taguchi Design

M Nayebsadrian,H Sadeghi,M Rostami,J Varshosaz,F Hassanzadeh,M Banitalebi

doi:10.1155/2012/860691

Abstract

Amphiphilic copolymers with self-assembling properties produce micelles in aqueous solutions and are made of two hydrophilic and hydrophobic segments. The objective of this study was optimization of the production of folate-conjugated dextran/retinoic acid (DEX/RA) micelles of doxorubicin. Micelles were prepared by direct dissolution method, and different effective parameters on their production were studied by a Taguchi design. The studied variables included CMC of the copolymer, polymer and drug contents, DEX Mw, stirring time, and rate and temperature. The effects of variables on responses of particle size, polydispersity index, zeta potential, drug loading, and release efficiency were studied. The most effective factors on particle size were DEX Mw, CMC of the copolymer, and stirring rate. Zeta potential and drug loading were more affected by the polymer content, DEX Mw, stirring time, and drug concentration. Stirring time and rate and also temperature of water were more effective variables on drug release rate. The optimum processing situation for micelles formation was obtained by copolymers with CMC <17 μg/mL and prepared from 20.1 mg copolymers of DEX Mw of 10000 and drug concentration of 15.9%. The optimized temperature for micelles formation was 40.7°C, and stirring time was 1 hr at a rate of 560 rpm.

Highlights

Amphiphilic copolymers with self-assembling properties produce micelles in aqueous solutions and are made of two hydrophilic and hydrophobic segments, with a large solubility difference
Retinoic acid was purchased from Solmag Chemical Company (Italy); doxorubicin HCl (Hangzhou ICH Biopharm Co., Ltd., Zhejiang, China) and folic acid were from Merck Chemical Company (Germany)
In these formulation codes the first digit represents the molecular weight of DEX, the second one stands for the feeding mole of retinoic acid (RA) per each mole of DEX, and the last one shows the feeding mole of the targeting moiety, that is, folic acid (FA)

Summary

Introduction

Amphiphilic copolymers with self-assembling properties produce micelles in aqueous solutions and are made of two hydrophilic and hydrophobic segments, with a large solubility difference. In comparison with other drug delivery systems, polymeric micelles have some advantages such as high stability, low critical micelle concentration (CMC), biodegradability, small particle size, high loading capacity, and prolonged circulation [2, 4]. For producing suitable polymeric micelles as drug delivery systems, development of new materials or improvement of existing materials has been tested over past years. Dextrans have been widely used because of their suitable properties such as nontoxicity, hydrophilic properties, nonimmunogenicity, stability, variety of molecular weights, low cost, and high ability of conjugation with other molecules via their large number of hydroxyl groups

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