title: Polymeric micelles with water-insoluble drug as hydrophobic moiety for drug delivery.
abstract: The hydrophobic block of polymeric micelles formed by amphiphilic copolymers has no direct therapeutical effect, and the metabolites of these hydrophobic segments might lead to some unexpected side effects. Here the hydrophobic core of polymeric micelles is replaced by highly water-insoluble drugs themselves, forming a new micellar drug delivery system. By grafting hydrophobic drugs of paclitaxel (PTX) onto the surface of hydrophilic hyperbranched poly(ether-ester) (HPEE), we constructed an amphiphilic copolymer (HPEE-PTX). HPEE-PTX could self-assemble into micellar nanoparticles in aqueous solution with tunable drug contents from 4.1 to 10.7%. Moreover, the hydrolysis of HPEE-PTX in serum resulted in the cumulative release of PTX. In vivo evaluation indicated that the dosage toleration of PTX in mice had been improved greatly and HPEE-PTX micellar nanoparticles could be used as an efficient prodrug with satisfactory therapeutical effect. We believe that most of the lipophilic drugs could improve their characters through this strategy.
authors.affiliation: School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
authors.forename: Guolin
authors.initials: G
authors.lastname: Li
authors.forename: Jinyao
authors.initials: J
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Pang
authors.forename: Ruibin
authors.initials: R
authors.lastname: Wang
authors.forename: Limin
authors.initials: L
authors.lastname: Mao
authors.forename: Deyue
authors.initials: D
authors.lastname: Yan
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D041681:NIH 3T3 Cells; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D011091:Polyesters / Q000138:chemical synthesis*; D051381:Rats; D012995:Solubility; D013501:Surface-Active Agents / Q000138:chemical synthesis*; D014867:Water
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D011091:Polyesters; D013501:Surface-Active Agents; D014867:Water; D017239:Paclitaxel