Daptomycin Proliposomes for Oral Delivery: Formulation, Characterization, and In Vivo Pharmacokinetics

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Nanotechnology

Background:

• Daptomycin (DAP) is a lipopeptide antibiotic primarily administered intravenously.
• Oral delivery of DAP is challenging due to poor bioavailability and stability.
• Proliposomes offer a promising strategy to improve oral drug delivery.

Purpose of the Study:

• To develop and characterize proliposomal formulations of daptomycin (DAP) for enhanced oral delivery.
• To evaluate the impact of phospholipids and charge modifiers on DAP encapsulation.
• To assess the in vitro and in vivo performance of the optimized DAP proliposomes.

Main Methods:

• Proliposomes were prepared using the thin film hydration method with various phospholipids (SPC, HEPC, DSPC) and cholesterol.
• Surface charge modifiers (DCP, SA) were incorporated to improve drug encapsulation.
• Physical characteristics (particle size, zeta potential, encapsulation efficiency) were assessed.
• In vitro drug release studies were conducted using USP type II apparatus.
• In vivo pharmacokinetic studies were performed in Sprague-Dawley rats.

Main Results:

• Soy-phosphatidylcholine (SPC)-based proliposomes showed higher entrapment efficiency compared to HEPC or DSPC.
• Optimized SPC-SA proliposomes achieved 92% encapsulation efficiency and a zeta potential of +28 mV.
• In vitro release demonstrated sustained drug retention, with <20% release in 60 min and 42% in 2 hours.
• Oral administration of SPC-SA proliposomes significantly increased DAP bioavailability in rats compared to drug solution.

Conclusions:

• Incorporating charge modifiers like stearylamine (SA) into soy-phosphatidylcholine (SPC) proliposomes enhances daptomycin (DAP) loading and oral delivery.
• The developed proliposomal formulation represents an attractive and effective carrier for oral administration of daptomycin.
• This approach holds potential for improving the therapeutic efficacy of daptomycin through oral administration.