title: Apamin-mediated actively targeted drug delivery for treatment of spinal cord injury: more than just a concept.
abstract: Faced with the complex medical challenge presented by spinal cord injuries (SCI) and considering the lack of any available curative therapy, the development of a novel method of delivering existing drugs or candidate agents can be perceived to be as important as the development of new therapeutic molecules. By combining three ingredients currently in clinical use or undergoing testing, we have designed a central nervous system targeted delivery system based on apamin-modified polymeric micelles (APM). Apamin, one of the major components of honey bee venom, serves as the targeting moiety, poly(ethylene glycol) (PEG) distearoylphosphatidylethanolamine (DSPE) serves as the drug-loaded material, and curcumin is used as the therapeutic agent. Apamin was conjugated with NHS (N-hydroxysuccinimide)-PEG-DSPE in a site-specific manner, and APM were prepared by a thin-film hydration method. A formulation comprising 0.5 mol % targeting ligand with 50 nm particle size showed strong targeting efficiency in vivo and was evaluated in pharmacodynamic assays. A 7-day treatment by daily intravenous administration of low doses of APM (corresponding to 5 mg/kg of curcumin) was performed. Significantly enhanced recovery and prolonged survival was found in the SCI mouse model, as compared to sham-treated groups, with no apparent toxicity. A single dose of apamin-conjugated polymers was about 700-fold lower than the LD50 amount, suggesting that APM and apamin have potential for clinical applications as spinal cord targeting ligand for delivery of agents in treatment of diseases of the central nervous system.
authors.affiliation: College of Pharmaceutical Sciences, Southwest University , Chongqing, 400715, P. R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wu
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Qiuyan
authors.initials: Q
authors.lastname: Bi
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Luo
authors.forename: Jianjun
authors.initials: J
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhangbao
authors.initials: Z
authors.lastname: Chen
authors.forename: Chong
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D001030:Apamin / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003474:Curcumin / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D051379:Mice; D008823:Micelles; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D013388:Succinimides / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008823:Micelles; D010714:Phosphatidylethanolamines; D011108:Polymers; D013388:Succinimides; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D001030:Apamin; D011092:Polyethylene Glycols; D003474:Curcumin; C001426:N-hydroxysuccinimide