title: Fabrication of biodegradable micelles with sheddable poly(ethylene glycol) shells as the carrier of 7-ethyl-10-hydroxy-camptothecin.
abstract: Biodegradable micelles with sheddable poly(ethylene glycol) shells were fabricated based on poly(ethylene glycol)-block-poly(γ-benzyl L-glutamate) (mPEG-SS-PBLG) diblock copolymer and applied as the carrier of 7-ethyl-10-hydroxy-camptothecin (SN-38) in order to enhance its solubility and stability in aqueous media. The diblock polymer was designed to have the hydrophilic PEG moiety and hydrophobic PBLG moiety linked by biodegradable disulfide bond, so in reducing environment the PEG shells can be detached. The polymer was able to form the micelles of nano-scale in aqueous media, suggesting their passive targeting potential to tumor tissue. Water-insoluble antitumor drug, SN-38, was easily encapsulated into mPEG-SS-PBLG nanomicelles by lyophilization method. When setting theoretical drug loading content at 10 wt%, the drug encapsulation efficiency (EE) was assayed as 73.5%. Owing to the disulfide bond in mPEG-SS-PBLG, intense release of SN-38 occurred in the presence of dithiothreitol (DTT) at the concentration of simulating the intracellular condition, however, micelles showed gradual release of SN-38 in the absence of DTT. Also, the mPEG-SS-PBLG micelles effectively protected the active lactone ring of SN-38 from hydrolysis under physiological condition. Compared with free SN-38, SN-38-loaded nanomicelles showed essentially decreased cytotoxicity against L929 cell line in 24h, bare mPEG-SS-PBLG nanomicelles showed almost non-toxicity.
authors: Institute of Drug Discovery and Development, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, PR China.
authors: Qian
authors: Q
authors: Guo
authors: Ping
authors: P
authors: Luo
authors: Yu
authors: Y
authors: Luo
authors: Fang
authors: F
authors: Du
authors: Wei
authors: W
authors: Lu
authors: Shiyuan
authors: S
authors: Liu
authors: Jin
authors: J
authors: Huang
authors: Jiahui
authors: J
authors: Yu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology; D001672:Biocompatible Materials / Q000138:chemical synthesis*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000138:chemical synthesis*; D004220:Disulfides / Q000737:chemistry; D004229:Dithiothreitol / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis*; D004339:Drug Compounding; D005612:Freeze Drying; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D000077146:Irinotecan; D007700:Kinetics; D051379:Mice; D008823:Micelles; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D012995:Solubility; D014867:Water
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004220:Disulfides; D004337:Drug Carriers; D008823:Micelles; D014867:Water; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; D000077146:Irinotecan; D004229:Dithiothreitol; D002166:Camptothecin