Journal
JOURNAL OF CONTROLLED RELEASE
Volume 79, Issue 1-3, Pages 165-172Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0168-3659(01)00537-5
Keywords
block copolymer micelles; controlled release; drug delivery; amphotericin B
Funding
- NIAID NIH HHS [AI43346-01] Funding Source: Medline
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The effect of tatty 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 phasphatidyglycerol (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 mug/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. (C) 2002 Elsevier Science B.V. All rights reserved.
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