Publication

Abstract :

Aim

Voriconazole (VRZ) is highly effective in treating invasive pulmonary aspergillosis (IPA), in addition to hepatotoxicity. Therefore, the current study focuses on the development and characterization of voriconazole-loaded microspheres (VRZ@PCL MSPs) to augment pulmonary localization and antifungal efficacy.

Methods

VRZ@PCL MSPs were fabricated by using the o/w emulsion method. The optimized F3VRZ@PCL MSPs were subjected to physicochemical characterization, in vitro release, hemocompatibility, antifungal efficacy as well as pharmacokinetic and biodistribution evaluation.

Results

The optimized F3VRZ@MSPs exhibited a particle size (10.90 ± 2.61 µm), entrapment efficiency (19.35 ± 2.47%), drug loading (3.22 ± 0.41%) with sustained release behavior up to 24 h and hemocompatibility upto 50 µg/mL. Results of antifungal testing indicated the superior antifungal potential of F3VRZ@PCL MSPs as compared to free VRZ and nystatin. In vivo pharmacokinetic evaluation in Sprague-Dawley rats displayed 12.5-fold and 4.5-fold increments, respectively, in t_1/2 and AUC_0-t of F3VRZ@PCL MSPs as compared to free VRZ. Moreover, F3VRZ@PCL MSPs displayed relatively higher lung targeting with a drug targeting index (DTI) of 0.213 as compared to DTI of 0.037 of free VRZ.

Conclusion

In conclusion, F3VRZ@PCL MSPs offer a promising approach for sustained and targeted delivery of VRZ and hold the potential to offer high therapeutic efficacy in the treatment of IPA.