Amphotericin B‐loaded poly(ethylene glycol)–poly(lactide) micelles: Preparation, freeze‐drying, and in vitro release

Abstract

Polymeric micelles prepared from a series of poly(ethylene glycol)-poly(lactide) (PEG-PLA) diblock copolymers with various PLA chain lengths were designed as drug carriers for water insoluble drug amphotericin B (AmB). Physicochemical properties of AmB-loaded micelles were evaluated. Micelles were freeze-dried to obtain long-time stable formulations. The redispersibility of the freeze-dried samples was poor when the weight ratio of PLA block was bigger than the PEG block of the copolymer. Various types of lyoprotectants including saccharides and PEGs with different molecular weight were tested to improve the redispersion performance of the freeze-dried samples. PEG was proved to be more effective than saccharides on stabilizing the micelles during lyophilization when the weight ratio of PLA block was bigger than PEG block. The sustained release in vitro of AmB was evidenced. About 80% of AmB was released in 80 h. The in vitro release behavior could be best described by the first-order equation. The release rate was reduced as enhancing PLA chain length due to the stronger interaction between poorly water-soluble AmB and longer hydrophobic chain length of PLA.

New delivery systems for amphotericin B applied to the improvement of leishmaniasis treatment

“…Such delivery systems for AmpB have been examined; Yang et al (40) formulated polymeric micelles prepared from a series of poly(ethylene glycol)-poly(lactide) (PLA) co-polymers with various polylactide chain lengths for AmpB. Shao et al (41) designed polymeric micelles using a formulation of 1,2-distearoyl-glycerol-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (PE-PEG)-based micelles loaded with AmpB, and they evaluated the presence and concentration of this drug in the brains of Sprague-Dawley rats.…”

Self-assembled amphotericin B-loaded polyglutamic acid nanoparticles: preparation, characterization and in vitro potential against Candida albicans

“…76 The stability of encapsulated AmB in serum has been extensively studied in other systems, including ones derived from polymers. 80,81 The AmB−PGA formulation showed better stability in PBS (pH 7.4) than AmB polymeric micelle systems, such as AmB-PEG-PLA (∼45% of AmB was released after 24 hours), 82 AmB-poly-lactic glycolic acid/dextran micelles (∼20% AmB released after 24 hours), AmB-PEG-PLA polymersomes (∼50% AmB released after 24 hours), 83 and AmB-poly(2-ethyl-2-oxazoline)-block-poly-(aspartic acid) polyion complex micelles (∼40% AmB released after 24 hours). 84 Furthermore, the stability of these polymeric micelle systems was only examined in PBS, and there have been no data available for serum.…”

Polymeric micelles: authoritative aspects for drug delivery

“…Drugs or copolymers prone to hydrolytic cleavage in aqueous systems may as well pose stability problems. However, lyophilized polymeric micelle formulations have shown to possess improved long-term stability for intravenously administered preparations [44][45][46].…”