title: Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation.
abstract: The aim of this work was to establish a novel polymeric mixed micelle composed of Pluronic P105 and F127 copolymers loaded with the poorly soluble antitumor drug docetaxel (DTX) against Taxol-resistant non-small cell lung cancer. A central composite design was utilized to optimize the preparation process, helping to improve drug solubilization efficiency and micelle stability. Prepared by a thin-film hydration method, the average size of the optimized mixed micelle was 23 nm, with a 92.40% encapsulation ratio and a 1.81% drug-loading efficiency. The optimized formulation showed high storage stability in lyophilized form, with 95.7% of the drug content remaining after 6 months' storage at 4°C. The in vitro cytotoxicity assay showed that the IC50 values for Taxotere(®) and mixed micelles were similar for A549, while on A549/Taxol cell lines, DTX-loaded P105/F127 mixed micelles showed a superior hypersensitizing effect; their IC50 value (0.059 μg/mL) was greatly reduced compared to those of Taxotere injections (0.593 μg/mL). The in vivo pharmacokinetic study showed that the mixed-micelle formulation achieved a 1.85-fold longer mean residence time in circulation and a 3.82-fold larger area under the plasma concentration-time curve than Taxotere. In addition, therapeutic improvement of mixed micelles in vivo against A549/Taxol was obtained. The tumor inhibition rate of the micelles was 69.05%, versus 34.43% for Taxotere (P < 0.01). Therefore, it could be concluded from the results that DTX-loaded P105/F127 mixed micelles might serve as a potential antitumor drug delivery system to overcome multidrug resistance in lung cancer.
authors: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China.
authors: Liangcen
authors: L
authors: Chen
authors: Xianyi
authors: X
authors: Sha
authors: Xinyi
authors: X
authors: Jiang
authors: Yanzuo
authors: Y
authors: Chen
authors: Qiuyue
authors: Q
authors: Ren
authors: Xiaoling
authors: X
authors: Fang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002152:Calorimetry, Differential Scanning; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D004355:Drug Stability; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D020442:Poloxamer / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D043823:Taxoids; D020442:Poloxamer; D000077143:Docetaxel; C519610:pluronic P105
keywords: docetaxel; multi-drug resistance; pluronic; polymeric micelle