Reverse polymeric micelles for pharmaceutical applications.
Star-shaped (4- to 8-arms) and linear poly(glycidyl methacrylate)s were synthesized by atom transfer radical polymerization as precursors of poly(glycerol methacrylate)s (PG(OH)MAs). The water-soluble PG(OH)MA backbones were modified through the esterification of pendant hydroxyl functions with acyl chlorides (12 to 18 carbons). Alkyated PG(OH)MAs were shown to self-assemble into reverse micelles (RMs) in organic solvents and/or oil. The resulting nanosized aggregates (20-60 nm) were able to reversibly extract anionic dyes from water and solubilise them in an organic phase. Furthermore, the encapsulation of vasopressin, a model peptide, in RMs significantly improved its solubility in an oily vehicle. This observation led to the development of water-free peptide formulations. In vitro release studies showed that the entrapped peptide slowly diffused out of an oily RM solution (<15% in 7 days). The release rate could be significantly increased upon emulsification of the oleaginous phase. In vivo, the subcutaneous administration of loaded RMs to rats significantly prolonged the pharmacological effect of vasopressin (>48 h vs. 8-10 h for an aqueous solution). These results highlight the ability of RMs to act as solubilizers for hydrophilic solutes in organic media, a property that may be exploited for applications in organic chemistry and pharmaceutical technology.
Canada Research Chair in Drug Delivery, Faculty of Pharmacy, University of Montreal, P.O. Box 6128, Downtown Station, Montreal, Quebec H3C3J7, Canada.
Marie-Christine
MC
Jones
Hui
H
Gao
Jean-Christophe
JC
Leroux
D000284:Administration, Oral; D000818:Animals; D050034:Antidiuretic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D004339:Drug Compounding; D007279:Injections, Subcutaneous; D007700:Kinetics; D008297:Male; D008823:Micelles; D015394:Molecular Structure; D053758:Nanoparticles; D009821:Oils / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000138:chemical synthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013501:Surface-Active Agents / Q000138:chemical synthesis*; D013678:Technology, Pharmaceutical / Q000379:methods; D014554:Urination / Q000187:drug effects; D014667:Vasopressins / Q000008:administration & dosage* / Q000737:chemistry
D050034:Antidiuretic Agents; D008823:Micelles; D009821:Oils; D011109:Polymethacrylic Acids; D012997:Solvents; D013501:Surface-Active Agents; D014667:Vasopressins; C042535:polyglycidyl methacrylate