title: Development and in vitro/in vivo evaluation of a novel targeted polymeric micelle for delivery of paclitaxel.
abstract: In this study a novel receptor-targeted micelle delivery system based on tocopherol succinate-chitosan-polyethylene glycol-folic acid (TS-CS-PEG-FA) was synthesized and loaded with paclitaxel (PTX). Physicochemical properties of the micelles such as critical micelle concentration, micelle size, entrapment efficiency, stability, release properties, cellular uptake and in vitro cytotoxicity were investigated in detail. Furthermore, the pharmacokinetics and tissue distributions of PTX-loaded micelles were evaluated in Balb/c mice and compared with Anzatax(®) (PTX in Cremophor EL(®)). Particle sizes and zeta potentials of the micelles were in the range of 162.3-277.1 nm and 18.5-28.3 mV, respectively. The drug entrapment efficiencies of the micelles were within 53.6-82.5% (w/w). Cytotoxicity assay demonstrated increased cytotoxic activity of PTX-loaded TS-CS-PEG-FA micelles compared to free PTX. The Vd and t1/2β of PTX-loaded TS-CS-PEG-FA were increased by 2.76- and 2.05-fold, respectively, while the plasma AUC of the micelles was only 0.76-fold lower than those of Anzatax(®) As demonstrated by tissue distribution, the PTX/TS-CS-PEG-FA micelles increased accumulation of PTX in tumor tissue. Therefore, the targeted chitosan derived micelle offered a stable and effective delivery system for PTX cancer chemotherapy.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Science, Isfahan, Iran.
authors.forename: Jaber
authors.initials: J
authors.lastname: Emami
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Science, Isfahan, Iran. Electronic address: rezazade@pharm.mui.ac.ir.
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Rezazadeh
authors.affiliation: Department of Medical Chemistry, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Science, Isfahan, Iran.
authors.forename: Farshid
authors.initials: F
authors.lastname: Hasanzadeh
authors.affiliation: Department of Biotechnology, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Science, Isfahan, Iran.
authors.forename: Hojjat
authors.initials: H
authors.lastname: Sadeghi
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Science, Isfahan, Iran.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Mostafavi
authors.affiliation: Department of Pharmacology, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Science, Isfahan, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Minaiyan
authors.affiliation: Department of Medical Chemistry, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Science, Isfahan, Iran.
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Rostami
authors.affiliation: Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Neal
authors.initials: N
authors.lastname: Davies
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D005260:Female; D006207:Half-Life; D006801:Humans; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008823:Micelles; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; D017239:Paclitaxel
keywords: Paclitaxel; Pharmacokinetics; Polymeric micelle