title: The effect of fatty acid substitution on the in vitro release of amphotericin B from micelles composed of poly(ethylene oxide)-block-poly(N-hexyl stearate-L-aspartamide).
abstract: The effect of fatty acid substitution on the in vitro release of amphotericin B (AmB) from micelles composed of poly(ethylene oxide)-block-poly[N-(6-hexyl stearate)-L-aspartamide] (PEO-b-PHSA) was investigated. PEO-b-PHSA at 11, 50 and 70% of stearic acid substitution self assembled into micelles that effectively encapsulate AmB by solvent evaporation and dialysis methods. The sustained release of AmB from PEO-b-PHSA micelles was evidenced, by measuring the transfer of the drug to lipid vesicles [dipalmitoyl phosphatidylcholine:cholesterol:dimyristoyl phosphatidyglycerol (3:1:0.25)]. The release of AmB for PEO-b-PHSA micelles was markedly influenced by the degree of fatty acid substitution--as it increased, the release of AmB slowed. Accordingly, drug release was found to correlate with haemolysis induced by AmB encapsulated in PEO-b-PHSA micelles. At 11% stearic acid substitution, encapsulation of AmB had little effect on the drug's ability to induce untoward haemolysis. In contrast, AmB stably encapsulated in PEO-b-PHSA micelles at 50 and 70% caused no hemolysis up to 20 microg/ml. Lastly, PEO-b-PHSA micelles at 50 and 70% were able to elute entirely as micelles during size-exclusion chromatography, indicating their stability toward dissociation after dilution. The results point to a nanoscopic drug depot that may release AmB at controlled rates.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Alberta T6G 2N8, Edmonton, Canada.
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Lavasanifar
authors.forename: John
authors.initials: J
authors.lastname: Samuel
authors.forename: Glen S
authors.initials: GS
authors.lastname: Kwon
mesh_terms: D000666:Amphotericin B / Q000737:chemistry / Q000493:pharmacokinetics*; D000935:Antifungal Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical; D005227:Fatty Acids / Q000737:chemistry* / Q000493:pharmacokinetics; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics*; D013228:Stearates / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D005227:Fatty Acids; D008823:Micelles; D013228:Stearates; D011092:Polyethylene Glycols; D000666:Amphotericin B