Development of Chitosan-Based Nanoemulsion Gel Containing Microbial Secondary Metabolite with Effective Antifungal Activity: In vitro and in vivo Characterizations

Abstract

Purpose Microbial resistance to antibiotics is one of the most important public health concerns of the 21 st century. We isolated, purified, and structurally elucidated antifungal secondary metabolites from red soil microbes and encapsulated them into chitosan (CS)-based nanoemulsion (NE) gel (NEG). Methods Three compounds were isolated and purified of which only one compound (Pure 2) showed potent antifungal activity (MFC: 8–132 µg/mL), which was also significantly ( P <0.05) more efficient than fluconazole (MFC: 32–132 µg/mL). Pure 2 was structurally elucidated using 1D- and 2D-NMR before its incorporation into NEG. The formulations were prepared by high-speed homogenization technique. Physicochemical and pharmacological characterizations of formulations (ie, droplet size, PDI, zeta potential, drug content, viscosity, SEM, FTIR, spreadability, in vitro drug release, ex vivo permeation, in vitro antifungal and in vivo antifungal activities) were assessed. Results NMR analyses identified the compound as a derivative of phthalic acid ester (PAE). The optimized formulations displayed a droplet size <100 nm, -ve zeta potential, and PDI <0.45. The drug content was within the official limit of pharmacopeia (ie, 100±10%). Insignificant changes ( P >0.05) in the viscosity of the formulations stored were observed. The morphology of the formulations indicated mesh-like structure. The FTIR study indicated that there were no interactions between the drug and other ingredients of the formulations. Optimum spreadability was observed in all formulations. NEG released 75.3±1.12% of Pure 2 after 12 hrs while NE released 85.33±1.88% of the compound. The skin permeation of F2 (71.15±1.28%) was significantly different ( P <0.05) from F3 (81.80±1.91%) in rabbits. Complete and apparently safe recovery from the fungal infection was achieved in rabbits treated topically with Pure 2-loaded NEGs. Conclusion Hence, the NEG-loaded PAE isolated from Pseudomonas fluorescens represents a possible alternative for the treatment of fungal infections as compared to available therapies.

Formulation and Characterization of Chitosan-Decorated Multiple Nanoemulsion for Topical Delivery In Vitro and Ex Vivo

“…The zeta potential value of prepared nanoemulsions was in the range of 2.88–3.61 mV. The positive value of zeta potential was accredited by the addition of chitosan [ 30 ]. The higher zeta potential value was credited to the addition of two surfactants (tween 80 and span 20) and a co-surfactant (PEG 400) to the formulation ( Table 2 ).…”

“…The drug content of the prepared MNE was 90 ± 2% on average, which was higher than the SNE and CNE. This showed good drug-loading capability for the prepared MNE, which was an important requirement for the nanoemulsion [ 30 ]. The higher drug content of the MNE was due to incorporation of chitosan and the double emulsion system.…”

Synthesis and In Vitro/Ex Vivo Characterizations of Ceftriaxone-Loaded Sodium Alginate/poly(vinyl alcohol) Clay Reinforced Nanocomposites: Possible Applications in Wound Healing

“…Previous studies showed that as the concentration of the drug is increased, the cumulative drug permeated is decreased. The films with the highest amount of drug gave the lowest values of the permeation [ 33 , 34 ]. We found similar findings (data not shown).…”

“…A CTX permeation study was performed through the rat skin using a Franz Diffusion Cell, following on previously published methods [ 8 , 33 , 34 ].…”

“…Dissolution testing is a requirement for all solid oral dosage forms and is widely used throughout the development life-cycle for evaluating the drug release characteristics and consistency/stability of a pharmaceutical product [ 22 , 28 , 29 , 34 ]. To study the dissolution of the CTX-loaded polymer nanocomposite, 25 mg of films was kept in a beaker containing 100 mL of 1× PBS at 37 °C.…”