Abstract
Propofol is a water-insoluble intravenous anesthetic agent that is actually formulated as a water-in-oil emulsion with known drawbacks such as pain on injection, microorganism growth support and stability. We report on the properties of formulations of propofol in poly (N-vinyl-2-pyrrolidone)-block-poly(D,L-lactide), PVP-PLA, polymeric micelles (Propofol-PM). Microbial growth in these formulations was evaluated with Pseudomonas aeruginosa (ATCC 9027), Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 25922) and Candida albicans (ATCC 10231). Sleep-recovery studies in female Sprague-Dawley rats, at a dose of 10mg/kg were performed to compare pharmacodynamic profiles of the new Propofol-PM formulations with those of Diprivan, a commercially available lipid based propofol formulation. Growth of microorganisms was not supported in the Propofol-PM formulations tested. No significant differences in times to unconsciousness, awakening, recovery of righting reflex and full recovery were observed between Propofol-PM formulations and Diprivan. Propofol loaded in PVP-PLA micelles (Propofol-PM) is not significantly different in terms of pharmacodynamic but demonstrates no microorganism growth support and improved stability that opens up the door to pain on injection reduction strategy.
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