Thermosensitive and biocompatible cyclotriphosphazene micelles.
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.
Toti
Udaya S
US
Division of Nano Science, Ewha Womans University, Daehyun-Dong 11 -1, Seodaemun-Ku, Seoul 120-750, Korea.
Moon
Sun Hee
SH
Kim
Hye Young
HY
Jun
Yong Joo
YJ
Kim
Byong Moon
BM
Park
Yong Man
YM
Jeong
Byeongmoon
B
Sohn
Youn Soo
YS
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
D004337:Drug Carriers; D008823:Micelles; D009570:Nitriles; D017553:Phosphorus Compounds; C068226:cyclotriphosphazene ester; D011092:Polyethylene Glycols