title: Thermosensitive and biocompatible cyclotriphosphazene micelles.
abstract: A new class of thermosensitive micellar cyclotriphosphazenes has been synthesized by stepwise nucleophilic substitutions of hexachlorocyclotriphosphazene with a hydrophilic methoxy poly(ethylene glycol) (MPEG) and a hydrophobic oligopeptide selected from tetra- to hexapeptides, and characterized by means of multinuclear ((1)H, (31)P) NMR spectroscopy, elemental analysis, and dynamic light scattering (DLS) method. All the amphiphilic trimers were found to form stable micelles by self-assembly in aqueous solution and to exhibit a lower critical solution temperature in the range of 20-48 degrees C in water depending on the hydrophilic to hydrophobic balance of the side groups. The micelles formed from the trimers bearing MPEG350 and a tetra- or pentapeptide were found to have a mean diameter of 13-14 nm, while, surprisingly, the trimers bearing longer MPEG550 and hexapeptides have shown remarkable contraction of their micelle size to a mean diameter of 7-8 nm, probably due to the strong intermolecular hydrophobic interactions among the hexapeptide groups of the trimers. The local tolerance tests using rabbits have shown excellent biocompatibility of the trimers. Also a promising in vitro releasing profile was obtained for local delivery of human growth hormone (hGH) as a model protein drug.
authors: Division of Nano Science, Ewha Womans University, Daehyun-Dong 11 -1, Seodaemun-Ku, Seoul 120-750, Korea.
authors: Udaya S
authors: US
authors: Toti
authors: Sun Hee
authors: SH
authors: Moon
authors: Hye Young
authors: HY
authors: Kim
authors: Yong Joo
authors: YJ
authors: Jun
authors: Byong Moon
authors: BM
authors: Kim
authors: Yong Man
authors: YM
authors: Park
authors: Byeongmoon
authors: B
authors: Jeong
authors: Youn Soo
authors: YS
authors: Sohn
mesh_terms: D000818:Animals; D001682:Biological Availability; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008823:Micelles; D009570:Nitriles / Q000737:chemistry* / Q000493:pharmacokinetics*; D017553:Phosphorus Compounds / Q000737:chemistry* / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics; D011817:Rabbits; D013696:Temperature
chemical_list: D004337:Drug Carriers; D008823:Micelles; D009570:Nitriles; D017553:Phosphorus Compounds; C068226:cyclotriphosphazene ester; D011092:Polyethylene Glycols