title: Construction and cellular uptake behavior of redox-sensitive docetaxel prodrug-loaded liposomes.
abstract: A redox-responsive docetaxel (DTX) prodrug consisting of a disulfide linkage between DTX and vitamin E (DTX-SS-VE) was synthesized in our laboratory and was successfully formulated into liposomes. The aim of this study was to optimize the formulation and investigate the cellular uptake of DTX prodrug-loaded liposomes (DPLs). The content of DTX-SS-VE was determined by ultrahigh-performance liquid chromatography (UPLC). The formulation and process were optimized using entrapment efficiency (EE), drug-loading (DL), particle size and polydispersity index (PDI) as the evaluation indices. The optimal formulation was as follows: drug/lipid ratio of 1:12, cholesterol/lipid ratio of 1:10, hydration temperature of 40 °C, sonication power and time of 400 W and 5 min. The EE, DL and particle size of the optimized DPLs were 97.60 ± 0.03%, 7.09 ± 0.22% and 93.06 ± 0.72 nm, respectively. DPLs had good dilution stability under the physiological conditions over 24 h. In addition, DPLs were found to enter tumor cells via different pathways and released DTX from the prodrug to induce apoptosis. Taken together, the optimized formulation and process were found to be a simple, stable and applicable method for the preparation of DPLs that could successfully escape from lysosomes.
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Shanxi Medical University , Shanxi , China.
authors.forename: Guolian
authors.initials: G
authors.lastname: Ren
authors.affiliation: b Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Mengjuan
authors.initials: M
authors.lastname: Jiang
authors.affiliation: b Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Weiling
authors.initials: W
authors.lastname: Guo
authors.affiliation: b Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Bingjun
authors.initials: B
authors.lastname: Sun
authors.affiliation: b Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: He
authors.initials: H
authors.lastname: Lian
authors.affiliation: b Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: b Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001692:Biological Transport; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D010084:Oxidation-Reduction / Q000187:drug effects*; D010316:Particle Size; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry*; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry*; D014810:Vitamin E / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D011355:Prodrugs; D043823:Taxoids; D014810:Vitamin E; D000077143:Docetaxel
keywords: Docetaxel; cellular uptake; formulation; liposome; optimization