Poloxamer 188 stabilized poly (ε-caprolactone) microspheres of voriconazole for targeting pulmonary aspergillosis.

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 and AUC 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.