Micelles of poly(ethylene oxide)-block-poly(N-alkyl stearate L-aspartamide): synthetic analogues of lipoproteins for drug delivery.
Stearic acid esters of poly(ethylene oxide)-block-poly(hydroxyethyl L-aspartamide) and poly(ethylene oxide)-block-poly(hydroxyhexyl L-aspartamide) have been synthesized from poly(ethylene oxide)-block-poly(beta-benzyl L-aspartate) by polymer-analogous reactions and self-assembled into a micelle. Transmission electron microscopy and fluorescent probe studies reveal that the micelle mimics structural features of serum lipoproteins: it is nanoscopic, spherical, and has a supramolecular core-shell architecture, where the core is rich in fatty acid esters. As a result, the polymeric micelles effectively solubilize amphotericin B, a key drug for systemic mycoses. Serum lipoproteins solubilize many hydrophobic drugs as a biological transport system besides amphotericin B. A synthetic polymeric analogue may achieve the same aim, but with the ease of structural modification, safety, and stability.
Lavasanifar
A
A
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2N8, Canada.
Samuel
J
J
Kwon
G S
GS
D000666:Amphotericin B / Q000008:administration & dosage / Q000737:chemistry; D001224:Aspartic Acid; D001704:Biopolymers; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008074:Lipoproteins / Q000737:chemistry; D008823:Micelles; D008854:Microscopy, Electron; D015394:Molecular Structure; D011091:Polyesters / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D012995:Solubility
D001704:Biopolymers; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008074:Lipoproteins; D008823:Micelles; D011091:Polyesters; D011506:Proteins; C416208:poly(ethylene oxide)-block-poly(N-ethyl stearate) aspartamide; C416209:poly(ethylene oxide)-block-poly(N-hexyl stearate) aspartamide; C416210:poly(ethylene oxide)-block-poly(beta-benzyl aspartate); D001224:Aspartic Acid; D011092:Polyethylene Glycols; D000666:Amphotericin B