The core-forming blocks of amphiphilic diblock copolymers based on methoxypoly(
ethylene oxide)-block-poly(
L-aspartate), PEO-b-p(L-Asp), were derivatized to incorporate
stearate side chains. The effects of
stearate esterification were assessed in terms of
micelle stability and
amphotericin B (AmB) encapsulation/release. The level of
stearate esterification modulates the relative self-aggregation state of encapsulated AmB as evidenced by absorption spectroscopy. When AmB is physically loaded into polymeric
micelles, the onset of hemolytic activity toward bovine erythrocytes is delayed relative to that of the free
drug. Furthermore, the extent of esterification (0, 46, or 91%) appears to have profound influence on the time-dependent hemolytic profile of AmB toward bovine erythrocytes. Particularly in the case of highly substituted
stearate ester micelles, incomplete and gradual build-up of
hemolysis was observed over a period of 24 h. On the basis of the corresponding absorption spectra, we speculate that encapsulated AmB may interact strongly with
stearate side chains, resulting in sustained release. In a neutropenic murine model of disseminated
candidiasis, kidney colony-forming unit determination revealed dose-dependent efficacy for the polymeric
micelle/AmB formulation, which was not significantly different from that of
Fungizone at doses of 0.2, 0.3, and 0.6 mg/kg (p = 0.7). Thus, AmB administered via a polymeric
micelle formulation retained potent in vivo activity.