Development and optimization of cilostazol loaded transethosomal gel for improved performance

Area of Science:

• Pharmaceutical Sciences
• Nanotechnology
• Drug Delivery Systems

Background:

• Deep vein thrombosis (DVT) is a significant cause of mortality, with oral cilostazol (CLZ) being a common treatment.
• Oral CLZ administration presents challenges including gastrointestinal side effects and extensive first-pass metabolism.
• Transdermal drug delivery offers a potential alternative to overcome oral administration limitations.

Purpose of the Study:

• To develop and optimize CLZ-loaded transethosomes (CLZ-TEs) incorporated into a chitosan gel (CLZ-TEG) for transdermal administration.
• To evaluate the physicochemical properties, in vitro release, permeation, skin irritation, and pharmacokinetic profile of the CLZ-TEG formulation.
• To compare the efficacy of CLZ-TEG with conventional oral formulations.

Main Methods:

• CLZ-TEs were optimized using Box-Behnken Design Expert software.
• Characterization included particle size, polydispersity index, zeta potential, entrapment efficiency, Transmission Electron Microscopy (TEM), and Fourier Transform Infrared Spectroscopy (FTIR).
• In vitro release, permeation studies, skin irritation tests, and pharmacokinetic evaluations were performed.

Main Results:

• Optimized CLZ-TEs exhibited favorable characteristics: 174 nm particle size, 0.173 PDI, -30 mV zeta potential, and 99% entrapment efficiency.
• TEM confirmed spherical nanovesicles, and FTIR indicated good excipient compatibility.
• CLZ-TEG demonstrated sustained release, enhanced CLZ permeation, and significantly improved bioavailability compared to oral CLZ formulations (p < 0.05).

Conclusions:

• CLZ-TEG is a promising transdermal formulation for DVT management.
• This formulation overcomes the limitations of oral CLZ administration.
• CLZ-TEG offers improved bioavailability and potentially reduced side effects for DVT patients.