Oral Gel Loaded by Fluconazole‒Sesame Oil Nanotransfersomes: Development, Optimization, and Assessment of Antifungal Activity

Abstract

Candidiasis is one of the frequently encountered opportunistic infections in the oral cavity and can be found in acute and chronic presentations. The study aimed to develop fluconazole-loaded sesame oil containing nanotransfersomes (FS-NTF) by the thin-layer evaporation technique to improve the local treatment of oral candidiasis. Optimization of the formulation was performed using the Box‒Behnken statistical design to determine the variable parameters that influence the vesicle size, entrapment efficiency, zone of inhibition, and ulcer index. Finally, the formulated FS-NTF was embedded within the hyaluronic acid‒based hydrogel (HA-FS-NTF). The rheological behavior of the optimized HA-FS-NTF was assessed and the thixotropic behavior with the pseudoplastic flow was recorded; this is desirable for an oral application. An in vitro release study revealed the rapid release of fluconazole from the HA-FS-NTF. This was significantly higher when compared with the fluconazole suspension and hyaluronic acid hydrogel containing fluconazole. Correspondingly, the ex vivo permeation was also found to be higher in HA-FS-NTF in sheep buccal mucosa (400 μg/cm2) when compared with the fluconazole suspension (122 μg/cm2) and hyaluronic acid hydrogel (294 μg/cm2). The optimized formulation had an inhibition zone of 14.33 ± 0.76 mm and enhanced antifungal efficacy for the ulcer index (0.67 ± 0.29) in immunocompromised animals with Candida infection; these findings were superior to those of other tested formulations. Hence, it can be summarized that fluconazole can effectively be delivered for the treatment of oral candidiasis when it is entrapped in a nanotransfersome carrier and embedded into cross-linked hyaluronic acid hydrogel.

Development, optimization, and evaluation of a nanostructured lipid carrier of sesame oil loaded with miconazole for the treatment of oral candidiasis

“…It means the SO-to-Compritol ratio and Labrasol concentration of the NLCs could restrict fungal growth in the selected medium with their increased concentrations. The reasons for this were the antifungal activity of SO (Lavaee et al., 2019 ) and the emulsification property of Labrasol, which increased the antifungal activity via the accelerating permeability (Alkhalidi et al., 2021 ) of MZ-SO-loaded NLCs. Additionally, the contour plot and 3D surface plot ( Figure 4 ) exhibited the impacts of independent factors on the inhibition zone of various fabricated NLCs.…”

“…The MZ-SO NLC, MZ suspension, and marketed MZ gel were applied for the first 3 days and at the end of 3 days (Al-Yahya & Asad, 2016 ; Mostofa et al., 2017 ). The mucosal ulceration index was calculated with a score of 0–5, where 0 was the normal architecture of epithelial cells; 1 was the epithelial cells with redness; 2 was ulcers of less than 3 mm, 3 was ulcers of 1–2 mm without hemorrhage, 4 was ulcers of 1–2 mm with hemorrhage, and 5 was ulcers of greater than 2 mm (Alkhalidi et al., 2021 ). The results were recorded, and the effects of the formulations on the ulcer index were analyzed via a one-way ANOVA test.…”

Molecular Mapping of Antifungal Mechanisms Accessing Biomaterials and New Agents to Target Oral Candidiasis

“…This intimate contact can be found under the concept of bioadhesion [ 204 ], a phenomenon that can be explained using a series of theories. The fundamentals of polymer–mucosal film interactions represent a cumulus of electronic, adsorption, wettability, diffusion, breaking, and mechanical phenomena which serve to develop polymeric-based materials such as mucoadhesive tablets [ 110 ], oromucosal gels [ 205 ], polymeric films [ 14 ], or polymeric-based supports enriched with nanoparticles [ 175 ]; the last two cases define advanced drug delivery systems for antifungals delivery.…”

Bioengineered Biomimetic and Bioinspired Noninvasive Drug Delivery Systems

“…[117] Another example was suggested by Alkhalidi et al who incorporated transferosomes containing sesame oil embedded within a hyaluronic acid hydrogel to improve the treatment of oral candidiasis. [118] Fibrin-a biopolymer with key roles in maintaining hemostasis and wound-healing-was augmented with PEG in order to produce a scaffold to be administered in the mouth cavity to treat small dental defects. [119] Another interesting approach is the chewing gum technology, used for extending buccal retention time.…”