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Synthesis and Characterization of Folate-Targeted Dextran/Retinoic Acid Micelles for Doxorubicin Delivery in Acute Leukemia Publisher Pubmed



Varshosaz J1 ; Hassanzadeh F2 ; Sadeghi Aliabadi H3 ; Nayebsadrian M1 ; Banitalebi M1 ; Rostami M2
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutics, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan 81746-73461, P.O. Box 81745-359, Iran
  2. 2. Department of Medicinal Chemistry, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan 81746-73461, P.O. Box 81745-359, Iran
  3. 3. Department of Biotechnology, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan 81746-73461, P.O. Box 81745-359, Iran

Source: BioMed Research International Published:2014


Abstract

Folate and retinoic acid grafted/dextran (FA-RA/DEX) copolymers with different molecular weight of DEX were synthesized using carbonyldiimidazole and dimethylaminopyridine for targeted delivery of doxorubicin (DOX) in acute myelogenous leukemia (AML). The copolymers structure was confirmed by 1H NMR and FTIR. Critical micelle concentration (CMC) of each copolymer was determined using pyrene as a fluorescent probe. DOX was loaded in micelles by the direct dissolution method. Physical properties of micelles, including particle size, zeta potential, drug loading efficiency, and drug release profiles, were examined. The orientation of the folate ligand on the surface of the micelles was studied by X-ray photoelectron spectroscopy (XPS) technique. The cytotoxicity of micelles loaded with DOX at different concentrations was studied in KG1 cells using MTT assay and their cellular uptake by flow cytometry technique. FTIR and 1H NMR spectra confirmed successful production of the targeted micelles and XPS spectra showed the surface orientation of folate. R15D10F7 copolymer produced micelles with particle size of 82.86 nm, polydispersity index of 0.3, zeta potential of -4.68 mV, drug loading efficiency of 96%, and release efficiency of 63%. DOX loaded in folate-targeted micelles of RA/DEX was more toxic than that in nontargeted micelles and free drug and seems promising in reducing drug resistance in AML. © 2014 J. Varshosaz et al.
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