Unimolecular micelles based on hydrophobically derivatized hyperbranched polyglycerols: biodistribution studies.
We recently reported the synthesis and testing of a new class of unimolecular micelles based on hyperbranched polyglycerols as second generation synthetic plasma expanders and as general drug delivery vehicles. A detailed biodistribution study of two derivatized hyperbranched polyglycerols of different molecular weights derivatized with hydrophobic groups and short poly(ethylene glycol) chains is reported in this article. In mice, these materials are nontoxic with circulation half-lives as high as 31 h, controllable by manipulating the molecular weight and the degree of PEG derivatization. Organ accumulation is low, presumably due to the "pegylation" effect. Thermal degradation and hydrolysis data suggest that these polymers are highly stable with a long shelf life, a major advantage for a pharmaceutical product. Degradation under acidic conditions has been observed for these polymers.
Department of Pathology and Laboratory Medicine, Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada.
Rajesh Kumar
RK
Kainthan
Donald E
DE
Brooks
D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D005260:Female; D005990:Glycerol / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D013696:Temperature; D014018:Tissue Distribution; D014867:Water / Q000737:chemistry
D001672:Biocompatible Materials; D008823:Micelles; D011108:Polymers; D014867:Water; C043941:polyglycerol; D005990:Glycerol