title: Co-delivery of paclitaxel and α-tocopherol succinate by novel chitosan-based polymeric micelles for improving micellar stability and efficacious combination therapy.
abstract: The aim of this study was to develop chitosan derivative polymeric micelles for co-delivery of paclitaxel (PTX) and α-tocopherol succinate (α-TS) to the cancer cells to improve the therapeutic efficiency and reduce side effects of PTX. In this study, amphiphilic tocopheryl succinate-grafted chitosan oligosaccharide was synthesized and physically loaded by PTX and α-TS with entrapment efficiency of 67.9% and 73.2%, respectively. Physical incorporation of α-TS into the micelles increased the hydrophobic interaction between PTX and the micelles core, which improved micelle stability, reduced the micelle size and also sustained the PTX release from the micelles. The mean particle size and zeta potential of αTS/PTX-loaded micelles were about 133 nm and +25.2 mV, respectively, and PTX release was completed during 6-9 d from the micelles. Furthermore, the cytotoxicity of α-TS/PTX-loaded micelles against human ovarian cancer cell line cancer cell in vitro was higher than that of PTX-loaded micelles and the free drug solution. Half maximal inhibitory concentration values of PTX after 48-h exposure of the cells to the PTX-loaded micelles modified and unmodified with α-TS were 110 and 188 ng/ml, respectively.
authors.affiliation: Department of Pharmaceutics .
authors.forename: Jaber
authors.initials: J
authors.lastname: Emami
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Rezazadeh
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Rostami
authors.forename: Farshid
authors.initials: F
authors.lastname: Hassanzadeh
authors.forename: Hojjat
authors.initials: H
authors.lastname: Sadeghi
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Mostafavi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Minaiyan
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Lavasanifar
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D004338:Drug Combinations; D016503:Drug Delivery Systems; D004355:Drug Stability; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D009844:Oligosaccharides / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D010316:Particle Size; D024502:alpha-Tocopherol / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D004338:Drug Combinations; D008823:Micelles; D009844:Oligosaccharides; D048271:Chitosan; D024502:alpha-Tocopherol; D017239:Paclitaxel
keywords: controlled drug release; paclitaxel; synergistic chemotherapy; α-tocopherol succinate