title: Redox-sensitive micelles assembled from amphiphilic mPEG-PCL-SS-DTX conjugates for the delivery of docetaxel.
abstract: Docetaxel (DTX) can produce anti-tumor effects by inhibiting cell growth and inducing apoptosis. However, the poor solubility of DTX restricts its application and its clinical formulation has caused serious adverse reaction due to the use of Tween-80. In the present study, DTX was conjugated to an amphiphilic di-block polymer to solve these problems. Methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) was selected as the polymer skeleton and a redox sensitive disulfide bond was used as the linker between DTX and mPEG-PCL. The synthesized mPEG-PCL-SS-DTX conjugates were characterized by (1)H-nuclear magnetic resonance ((1)H NMR) and Fourier transform infrared spectroscopy (FTIR). Interestingly, the mPEG-PCL-SS-DTX conjugates could self-assemble into micelles in aqueous solution. The critical micelle concentration (CMC) of mPEG-PCL-SS-DTX micelles was about 2.3mgL(-1) determined using pyrene molecule fluorescent probe method while the size of mPEG-PCL-SS-DTX micelles was determined to be ca. 17.6nm and 116.0nm with a bimodal distribution by dynamic light scattering (DLS). The in vitro release results indicated that the as-prepared micelles exhibited a sustained release profile with good redox sensitive properties. In particular, the hemolytic toxicity test indicated the as-prepared mPEG-PCL-SS-DTX micelles had negligible hemolytic activity, demonstrating their safety in drug delivery system. Cytotoxicity assay of the mPEG-PCL-SS-DTX micelles verified their highly enhanced cytotoxicity to MCF-7/A and A549 cells. These results thus demonstrated that the present redox-sensitive mPEG-PCL-SS-DTX micelle was an efficient and safe sustained drug delivery system in the biomedical area.
authors.affiliation: School of Pharmaceutical Science, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province 250012, PR China.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Science, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province 250012, PR China.
authors.forename: Kaiming
authors.initials: K
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Science, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province 250012, PR China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Science, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province 250012, PR China.
authors.forename: Wenxiu
authors.initials: W
authors.lastname: He
authors.affiliation: Key Lab of Colloid & Interface Chemistry, Shandong University, Ministry of Education, 250100, PR China.
authors.forename: Aixin
authors.initials: A
authors.lastname: Song
authors.affiliation: School of Pharmaceutical Science, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province 250012, PR China. Electronic address: yuxialuan@sdu.edu.cn.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Luan
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D065546:Drug Liberation; D019008:Drug Resistance, Neoplasm; D004912:Erythrocytes; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D061986:MCF-7 Cells; D008823:Micelles; D010084:Oxidation-Reduction; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000378:metabolism; D011721:Pyrenes / Q000737:chemistry; D011817:Rabbits; D012995:Solubility; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008823:Micelles; D011091:Polyesters; D011721:Pyrenes; D043823:Taxoids; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D000077143:Docetaxel; D011092:Polyethylene Glycols; C030984:pyrene
keywords: Docetaxel; Drug delivery; MPEG-PCL; Polymeric micelle; Redox-sensitive