RESUMO
Fungal infections (FIs) affect majority of the population, but the current treatments face challenges in terms of their effectiveness. This study focused on specific fungal targets, including dihydrofolate reductase (DHFR), acetohydroxy-acid synthase (AHAS), farnesyltransferase and endoglucanase. The docking studies were conducted with the drug voriconazole (VCZ), comparing it with Fluconazole (FCZ) and Amphotericin B (ATB) against 11 protein data bank (PDB) IDs (IDYR, 3NZB, 6DEQ, 1KS5, 7T0C, 1FY4, 5AJH, 7R79, 6TZ6 and 6IDY). Molecular dynamics (MD) analysis, including RMSD, RMSF, PCA and FEL, confirmed the stability of VCZ. The solubility of VCZ was a problem, so nanostructured lipid carriers (NLCs) were developed to improve ocular penetration. VCF5 was the optimized formulation by using 32 full factorial design. VCZF5-NLCs were the best in terms of nanoparticle size (126.6 nm), Zeta potential (33.5 mV), drug content (DC; 97.38 ± 0.210), encapsulation efficiency (EE; 88.01 ± 0.272) and extended drug release. The results of the ex-vivo corneal diffusion study indicate that VCZ-NLC-loaded in-situ gel (VCZ-NLC-IG3) exhibited DC of 88.25% and drug entrapment (DE) of 74.2%. The results of the zone of inhibition indicated that VCZ-NLC-IG3 had superior efficacy compared to ATB. Network pharmacology showed VCZ interacts with the genes which are responsible for fungus ergosterol biosynthesis, including lanosterol 14-alpha demethylase inhibitors (ERG11), ergosterol biosynthesis protein 5 (ERG5), dimethylallyltransferase 2 (DIT2), ketosynthase (KCN), methylsterol monooxygenase (MSMO1), lamin B receptor (LBR), squalene epoxidase (SQLE), 3-hydroxy-3-methylglutaryl-coenzyme A Reductase (MGCR), 3-hydroxy-3-methylglutaryl-coenzyme A Synthase (HMGCS) and 3-keto-steroid reductase (HSD17B7). In conclusion, the optimized VCZ-loaded NLCs present a promising approach to treat ocular FIs.Communicated by Ramaswamy H. Sarma.
RESUMO
Currently, various kinds of research are going in the evolution of the Novel Drug Delivery System. NDDS mainly emphasizes the development of a system with improved sustained, controlled, and targeted drug delivery with minimum toxicity. Proniosomes are dry free-flowing formulation that minimizes the drawbacks associated with liposomes and niosomes. Proniosomes are carrier particles that are water-soluble and covered with a surfactant which, upon hydration in a hot aqueous medium with agitation, gives niosomal dispersion. Proniosomes derived niosomes are superior substitutes as compared to other vesicular delivery due to preferable physicochemical properties and improved chemical stability. The proniosomes deliver additional convenience of transportation, storage, distribution, and dosing, which makes dry niosomes a versatile commercial product. This illustrated review emphasizes the components, method of preparation, factors affecting the formation of proniosomes, characterization, and various routes of administration of proniosomes. This review will help to explore the efficacy and functionality of proniosomes in different fields for their upcoming supremacy in the field of drug delivery.
