Cyclodextrin Stabilized Freeze-Dried Silica/Chitosan Nanoparticles for Improved Terconazole Ocular Bioavailability

Area of Science:

• Materials Science
• Pharmaceutical Sciences
• Nanotechnology

Background:

• Terconazole is a poorly water-soluble antifungal agent.
• Ocular drug delivery faces challenges with poorly soluble drugs.
• Nanoparticle-based systems offer potential for improved ocular drug delivery.

Purpose of the Study:

• To develop and optimize silica/chitosan nanoparticles (SCNs) for ocular delivery of terconazole.
• To assess the physicochemical properties and in vitro performance of terconazole-loaded SCNs.
• To evaluate the in vivo pharmacokinetic profile and safety of SCNs for ocular application.

Main Methods:

• Fabrication of SCNs using tetraethyl ortho silicate (TEOS) and chitosan HCl.
• Optimization using a 2^3.3^1 full factorial design.
• Characterization by particle size, PDI, yield, drug loading, DSC, XRD, FTIR, and morphology.
• In vitro release studies and in vivo pharmacokinetic assessment in rabbits.

Main Results:

• Nanoparticle size and yield were influenced by water and TEOS content.
• Optimized SCNs exhibited good mucoadhesion and safety in rabbit eyes.
• In vivo studies showed higher Cmax and AUC0-24 with longer tmax for SCNs compared to terconazole suspension.

Conclusions:

• SCNs are effective carriers for ocular delivery of poorly water-soluble drugs like terconazole.
• The developed SCNs demonstrate potential for enhanced ocular bioavailability and sustained drug release.
• This formulation offers a promising approach for treating ocular fungal infections.