Jun-Pil Jee1, Aaron McCoy, Sandro Mecozzi. 1. School of Pharmacy, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, USA.
Abstract
PURPOSE: PEG-phospholipid-based micelles have been successfully used for the solubilization of several hydrophobic drugs but generally lack sustained stability in blood. Our novel PEG-Fluorocarbon-DSPE polymers were designed to increase stability and improve time-release properties of drug-loaded micelles. METHODS: Novel ABC fluorous copolymers were synthesized, characterized, and used for encapsulation release of amphotericin B. FRET studies were used to study micelle stability. RESULTS: The micelles formed by the new polymers showed lower critical micelle concentrations and higher viscosity cores than those formed by the polymers lacking the fluorous block. FRET studies indicated that fluorocarbon-containing micelles had increased stability in presence of human serum. Physicochemical properties and in vitro release profile of micelles loaded with Amphotericin B (AmB) were studied. CONCLUSIONS: The effect of PEG length and fluorocarbon incorporation were investigated. The shorter hydrophilic PEG2K induced greater stability than PEG5K by decreasing the proportion of hydrophilic block of the polymer. The fluorocarbon placed between hydrophilic and hydrophobic block formed a fluorous shell contributing to the enhanced thermodynamic stability of micelles and to the drug sustained release. Polymer mPEG2K-F(10)-DSPE, bearing both a fluorocarbon block and a shorter mPEG, showed the greatest stability and the longest half-life for AmB release.
PURPOSE:PEG-phospholipid-based micelles have been successfully used for the solubilization of several hydrophobic drugs but generally lack sustained stability in blood. Our novel PEG-Fluorocarbon-DSPE polymers were designed to increase stability and improve time-release properties of drug-loaded micelles. METHODS: Novel ABCfluorous copolymers were synthesized, characterized, and used for encapsulation release of amphotericin B. FRET studies were used to study micelle stability. RESULTS: The micelles formed by the new polymers showed lower critical micelle concentrations and higher viscosity cores than those formed by the polymers lacking the fluorous block. FRET studies indicated that fluorocarbon-containing micelles had increased stability in presence of human serum. Physicochemical properties and in vitro release profile of micelles loaded with Amphotericin B (AmB) were studied. CONCLUSIONS: The effect of PEG length and fluorocarbon incorporation were investigated. The shorter hydrophilic PEG2K induced greater stability than PEG5K by decreasing the proportion of hydrophilic block of the polymer. The fluorocarbon placed between hydrophilic and hydrophobic block formed a fluorous shell contributing to the enhanced thermodynamic stability of micelles and to the drug sustained release. Polymer mPEG2K-F(10)-DSPE, bearing both a fluorocarbon block and a shorter mPEG, showed the greatest stability and the longest half-life for AmB release.
Authors: Bushra T Al-Quadeib; Mahasen A Radwan; Lidija Siller; Benjamin Horrocks; Matthew C Wright Journal: Saudi Pharm J Date: 2014-11-20 Impact factor: 4.330