Development and characterization of optimized sustained release voriconazole-loaded chitosan nanoparticles for ocular delivery

Document Type : Research Article


1 Tehran University of Medical Sciences, International Campus, Tehran, Iran

2 Chemical Engineering Department, Varamin-Pishva Branch, Islamic Azad University, Varamin, Iran

3 School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

5 Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran


Voriconazole is an approved antifungal agent belonging to the triazole family. It is generally used for treating aggressive fungal infections such as invasive candidiasis or aspergillosis, as well as certain fungal infections, in immunocompromised patients. Voriconazole has an oral bioavailability of 96%, and patients can receive the medication either by oral or parenteral routes. To fabricate a topical ocular voriconazole delivery system, we prepared voriconazole-loaded chitosan nanoparticles by ionic gelation of chitosan with the addition of sodium tripolyphosphate (TPP). Three chitosan polymers with different molecular weights were tested by varying chitosan and TPP concentrations, and the produced nanoparticles were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and x-ray powder diffraction (XRD). The obtained data was presented into a Box-Behnken design, which showed a set of optimum parameters that would yield an optimized formulation with the most favourable properties. Subsequently, the optimized formulation was synthesized, and the voriconazole release from this formulation was monitored over 48 hr. Results showed the drug-loaded nanoparticles have high drug loading, show no burst effect, and sustain drug release for up to 48 hr. Therefore, this formulation is a potentially efficient ocular delivery system for voriconazole.

Graphical Abstract

Development and characterization of optimized sustained release voriconazole-loaded chitosan nanoparticles for ocular delivery


  • Particle size of nanoparticles were reduced by decreasing concentration of chitosan at constant pH.
  • At constant pH, by increasing the percentage of TPP from 5 to 20%, the EE% was raised dramatically.
  • The nanoparticles had a high thermal stability that indicated well-establishment of structure.
  • The release pattern indicated a very slow release of drug at each point of time from the nanoparticles.


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