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.
Jones
Marie-Christine
MC
Canada Research Chair in Drug Delivery, Faculty of Pharmacy, University of Montreal, P.O. Box 6128, Downtown Station, Montreal, Quebec H3C3J7, Canada.
Gao
Hui
H
Leroux
Jean-Christophe
JC
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