Block copolymer micelles for the encapsulation and delivery of amphotericin B.
OBJECTIVE
To assess the effect of fatty acid substitution of a micelle-forming poly(ethylene oxide)-block-poly(N-hexyl stearate-L-aspartamide) (PEO-b-PHSA) on the encapsulation, hemolytic properties and antifungal activity of amphotericin B (AmB).


METHODS
PEO-b-PHSA with three levels of stearic acid substitution were synthesized and used to encapsulate AmB by a solvent evaporation method. Size exclusion chromatography and UV spectroscopy were used to confirm and measure levels of encapsulated AmB. The hemolytic activity of encapsulated AmB toward human red blood cells and its minimum inhibitory concentration against Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans were obtained and compared to AmB alone.


RESULTS
An increase in the level of stearic acid substitution on PEO-b-PHSA improved the encapsulation of AmB while reducing its hemolytic activity. PEO-b-PHSA micelles having 50% and 70% stearic acid substitution (mol fatty acid: mol reacted and unreacted hydroxyls) were completely non-hemolytic at 22 microg/ml. At 11% stearic acid substitution, AmB caused 50% hemolysis at 1 microg/ml. AmB in PEO-b-PHSA micelles was as effective as AmB alone against pathogenic fungi.


CONCLUSIONS
PEO-b-PHSA micelles with a high level of stearic acid side chain substitution can effectively solubilize AmB, reduce its hemolytic activity yet retain its potent antifungal effects.
Lavasanifar
Afsaneh
A
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Samuel
John
J
Sattari
Saeed
S
Kwon
Glen S
GS
D000666:Amphotericin B / Q000008:administration & dosage* / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008823:Micelles; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry
D008823:Micelles; D011108:Polymers; D000666:Amphotericin B