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Synthesis of Biotin-Targeted Chitosan/Poly (Methyl Vinyl Ether- Alt -Maleic Acid) Copolymeric Micelles for Delivery of Doxorubicin Publisher



Varshosaz J1 ; Khabbazian E1 ; Hassanzadeh F2 ; Sadeghi Aliabadi H3 ; Rostami M2 ; Taymouri S1
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutics, Faculty of Pharmacy, Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, 81745-359, Iran
  2. 2. Department of Medicinal Chemistry, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 81745-359, Iran

Source: IET Nanobiotechnology Published:2017


Abstract

Biotinylated chitosan/poly(methyl vinyl ether-alt-maleic acid) (PMVEMA) copolymer was synthesised by an amide reaction in two steps. Structural characterisation was performed using 1HNMR and Fourier transform infra-red (FTIR) spectra. Critical micelle concentration (CMC) of the copolymer was determined by pyrene as a fluorescent probe. Doxorubicin (DOX) was loaded in the micelles by the direct dissolution method. The effects of different variables including type of copolymer, copolymer concentration, stirring rate and stirring time were studied on the physicochemical properties of the micelles including: particle size, zeta potential, release efficiency and loading efficiency of nanoparticles using an irregular factorial design. The in vitro cytotoxicity of DOX-loaded biotin-targeted micelles was studied in HepG2 cells which over express biotin receptors by 3, 5-[dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide assay. The successful synthesis of the biotinylated copolymer of chitosan/PMVEMA was confirmed by FTIR and 1HNMR. The optimised micelles showed the CMC of 33 μg/ml, particle size of 247 ± 2 nm, zeta potential of +9.46 mV, polydispersity index of 0.22, drug-loading efficiency of 71% and release efficiency of 84.5 ± 1.6%. The synthesised copolymer was not cytotoxic. The cytotoxicity of DOX-loaded in targeted micelles on HepG2 cell line was about 2.2-fold compared with free drug. © The Institution of Engineering and Technology 2017.
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