Synthesis and characterization of folate-targeted dextran/retinoic acid micelles for doxorubicin delivery in acute leukemia.
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 (1)H 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 (1)H 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.
Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, P.O. Box 81745-359, Isfahan 81746-73461, Iran.
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J
Varshosaz
Department of Medicinal Chemistry, School of Pharmacy, Isfahan University of Medical Sciences, P.O. Box 81745-359, Isfahan 81746-73461, Iran.
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F
Hassanzadeh
Department of Biotechnology, School of Pharmacy, Isfahan University of Medical Sciences, P.O. Box 81745-359, Isfahan 81746-73461, Iran.
H
H
Sadeghi Aliabadi
Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, P.O. Box 81745-359, Isfahan 81746-73461, Iran.
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M
Nayebsadrian
Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, P.O. Box 81745-359, Isfahan 81746-73461, Iran.
M
M
Banitalebi
Department of Medicinal Chemistry, School of Pharmacy, Isfahan University of Medical Sciences, P.O. Box 81745-359, Isfahan 81746-73461, Iran.
M
M
Rostami
D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003911:Dextrans / Q000737:chemistry / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005492:Folic Acid / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008823:Micelles; D014212:Tretinoin / Q000737:chemistry / Q000494:pharmacology; D014803:Vitamin B Complex / Q000737:chemistry / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D003911:Dextrans; D004337:Drug Carriers; D008823:Micelles; D014803:Vitamin B Complex; D014212:Tretinoin; D004317:Doxorubicin; D005492:Folic Acid