Publisher's Synopsis
Revision with unchanged content. The potential of polymeric micelles formed from biocompatible or generally regarded as safe (GRAS) materials as sustained release nanocarriers for amphotericin B has been evaluated in this dissertation as further development can proceed without an explicit concern for biocompatibility which may slow progress of particulate carriers prepared from novel synthetic polymers. PEG-phospholipid (PEG-DSPE) micelles clearly prevented AmB induced toxicity pointing to stable drug incorporation, in vitro. However, drug release and absorption kinetics revealed that AmB was rapidly dissociated from PEG-DSPE micelles in serum albumin, a likely situation in vivo. Cholesterol co-incorporation influenced properties of PEG-DSPE micelles and slowed AmB release in serum albumin raising promise as long circulating carriers for AmB delivery. Further, AmB in PEG-DSPE micelles was stable in saline when combined with 5-fluorocytosine and solubilized rapamycin. Hence, PEG-DSPE micelles represent an interesting alternative to deoxycholate-AmB, particularly in combination therapy involving AmB with optional continuous infusion or sodium supplementation.
