Proliposomes as a drug delivery system to decrease the hepatic first-pass metabolism: case study using a model drug

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Biopharmaceutics

Background:

• Highly metabolized drugs often undergo significant first-pass metabolism, reducing oral bioavailability.
• Lovastatin, a common statin, is subject to extensive hepatic metabolism.
• Novel drug delivery systems are needed to overcome pharmacokinetic limitations of such drugs.

Purpose of the Study:

• To develop proliposomal formulations for lovastatin.
• To decrease the hepatic first-pass metabolism of lovastatin.
• To enhance the oral bioavailability of lovastatin.

Main Methods:

• Proliposomes were prepared using soy phosphatidylcholine (SPC), hydrogenated egg phosphatidylcholine (HEPC), and dimyristoyl phosphatidylglycerol (DMPG) with lovastatin and cholesterol.
• In vitro characterization included drug release studies and parallel artificial membrane permeability assay (PAMPA).
• In vivo studies in rats assessed the relative bioavailability of the optimized proliposomal formulation compared to pure lovastatin.

Main Results:

• Proliposomal formulations showed significantly higher in vitro drug release (85-96%) compared to pure lovastatin (48%) within 30 minutes.
• The optimized proliposomal formulation (F9) achieved a 162% relative bioavailability in rats after oral administration.
• Proliposomes effectively reduced the hepatic first-pass effect of lovastatin.

Conclusions:

• Proliposomes serve as an effective drug delivery system for improving the oral bioavailability of highly metabolized drugs like lovastatin.
• This approach can mitigate hepatic first-pass metabolism, offering a promising strategy for drug development.
• The developed proliposomal formulation demonstrates potential for clinical application in enhancing drug efficacy.