title: Transferrin-conjugated nanoparticles of poly(lactide)-D-alpha-tocopheryl polyethylene glycol succinate diblock copolymer for targeted drug delivery across the blood-brain barrier.
abstract: We developed in this research a nanoparticle system for targeted drug delivery across the blood-brain barrier (BBB), which consists of the transferrin (Tf) conjugated nanoparticles of poly(lactide)-D-alpha-Tocopheryl polyethylene glycol succinate (PLA-TPGS) diblock copolymer. The NPs were prepared by the nanoprecipitation method and characterized for their various physicochemical and pharmaceutical properties. Cellular uptake and cytotoxicity of the Tf-conjugated PLA-TPGS NPs formulation of coumarin 6 as a model imaging agent or Docetaxel as a model drug were investigated in close comparison with those for the PLGA NPs formulation, the bare PLA-TPGS NPs formulation as well as with the clinical Taxotere. The Tf-conjugated PLA-TPGS NPs formulation demonstrated great advantages over the other two NPs formulations and the original imaging/therapeutic agents. IC50 data showed that the Tf-conjugated PLA-TPGS NPs formulation of Docetaxel could be 23.4%, 16.9% and 229% more efficient than the PLGA NPs, the PLA-TPGS NPs formulations and Taxotere after 24 h treatment, respectively. Moreover, our preliminary ex vivo biodistribution investigation demonstrated that although not as satisfactory, the Tf-conjugated PLA-TPGS NPs formulation could be able to deliver imaging/therapeutic agents across the BBB.
authors.affiliation: Department of Chemical & Biomolecular Engineering, National University of Singapore, Singapore.
authors.forename: Chee Wee
authors.initials: CW
authors.lastname: Gan
authors.forename: Si-Shen
authors.initials: SS
authors.lastname: Feng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D003374:Coumarins / Q000737:chemistry / Q000378:metabolism; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008297:Male; D008422:Materials Testing; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013386:Succinates / Q000737:chemistry* / Q000378:metabolism; D043823:Taxoids / Q000737:chemistry / Q000378:metabolism; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism; D014018:Tissue Distribution; D014168:Transferrin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D003374:Coumarins; D004337:Drug Carriers; D013386:Succinates; D043823:Taxoids; D013844:Thiazoles; D014168:Transferrin; C517282:coumarin 6; C514223:poly(lactide)-tocopheryl polyethylene glycol succinate; D000077143:Docetaxel; D011092:Polyethylene Glycols