Formulation, optimization, and nephrotoxicity evaluation of an antifungal in situ nasal gel loaded with voriconazole‒clove oil transferosomal nanoparticles

Abstract

Fungal infections of the paranasal cavity are among the most widely spread illnesses nowadays. The aim of the current study was to estimate the effectiveness of an in situ gel loaded with voriconazole‒clove oil nano-transferosomes (VRC-CO-NT) in enhancing the activity of voriconazole against Aspergillus flavus , which causes rhinosinusitis. The nephrotoxic side effects of voriconazole may be reduced through the incorporation of the clove oil, which has antioxidant activity that protects tissue. The Box‒Behnken design was applied to formulate the VRC-CO-NT. The particle size, entrapment efficiency, antifungal inhibition zone, and serum creatinine concentration were considered dependent variables, and the soybean lecithin, VRC, and CO concentrations were considered independent ones. The final optimized formulation was loaded into a deacetylated gellan gum base and evaluated for its gelation, rheological properties, drug release profile, permeation capabilities, and in vivo nephrotoxicity. The optimum formulation was determined to be composed of 50 mg/mL lecithin, 18 mg/mL VRC, and 75 mg/mL CO, with a minimum particle size of 102.96 nm, an entrapment efficiency of 71.70%, an inhibition zone of 21.76 mm, and a serum creatinine level of 0.119 mmol/L. The optimized loaded in situ gel released 82.5% VRC after 12 hours and resulted in a 5.4-fold increase in drug permeation. The in vivo results obtained using rabbits resulted in a nonsignificant differentiation among the renal function parameters compared with the negative control group. In conclusion, nasal in situ gel loaded with VRC-CO-NT is considered an efficient novel carrier with enhanced antifungal properties with no signs of nephrotoxicity.

Carbon Nanotube Hybrid Materials: Efficient and Pertinent Platforms for Antifungal Drug Delivery

“…through routes such as intravenous, topical, and more. [3,15,32,35,[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] Their antifungal activities have been investigated against a diverse range of fungal species like Candida albicans, Candida tropicalis, Aspergillus flavus, Aspergillus niger, Cryptococcus tropicum, Trichophyton rubrum, Microsporum canis, Aspergillus nidulans, Microsporum gypseum, Microsporum canis, Trichophyton mentagrophytes, Saccharomyces cerevisiae, and others [3,15,32,35,[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] (Table 1).…”

L-Cysteine-Modified Transfersomes for Enhanced Epidermal Delivery of Podophyllotoxin

“…It is well known that the skin may act as a negatively charged membrane [26]. The electrostatic interaction between the negatively charged skin surface and the optimized formulation might cause temporary channels in the skin structure, favoring the delivery and retention of the drug down to the deeper skin [27][28][29]. According to previous studies, negatively charged nanocarriers could improve the skin permeability and retention of drugs in transdermal delivery [30].…”

Excipients Used for Modified Nasal Drug Delivery: A Mini-Review of the Recent Advances

“…In another study, nanotransferosomes were loaded into an in situ gel system for the biphasic release of voriconazole. Initial incomplete gel formation caused drug burst release, but in subsequent stages, gelation occurred and slower drug release was observed [ 51 ].…”