Development, characterization, and in vivo assessment of mucoadhesive nanoparticles containing fluconazole for the local treatment of oral candidiasis

Abstract

This study aimed to develop a suitable buccal mucoadhesive nanoparticle (NP) formulation containing fluconazole for the local treatment of oral candidiasis. The suitability of the prepared formulations was assessed by means of particle size (PS), polydispersity index, and zeta potential measurements, morphology analysis, mucoadhesion studies, drug entrapment efficiency (EE), in vitro drug release, and stability studies. Based on the optimum NP formulation, ex vivo drug diffusion and in vitro cytotoxicity studies were performed. Besides, evaluation of the antifungal effect of the optimum formulation was evaluated using agar diffusion method, fungicidal activity-related in vitro release study, and time-dependent fungicidal activity. The effect of the optimum NP formulation on the healing of oral candidiasis was investigated in an animal model, which was employed for the first time in this study. The zeta potential, mucoadhesion, and in vitro drug release studies of various NP formulations revealed that chitosan-coated NP formulation containing EUDRAGIT ® RS 2.5% had superior properties than other formulations. Concerning the stability study of the selected formulation, the formulation was found to be stable for 6 months. During the ex vivo drug diffusion study, no drug was found in receptor phase, and this is an indication of local effect. The in vitro antifungal activity studies showed the in vitro efficacy of the NP against Candida albicans for an extended period. Also, the formulation had no cytotoxic effect at the tested concentration. For the in vivo experiments, infected rabbits were successfully treated with local administration of the optimum NP formulation once a day. This study has shown that the mucoadhesive NP formulation containing fluconazole is a promising candidate with once-a-day application for the local treatment of oral candidiasis.

Development and in vitro Evaluation of Voriconazole Nanoparticle Formulation for Mucosal Application

“…The mucoadhesive NP was prepared by adapting the spontaneous emulsification technique previously described by Rençber et al, 18 which was the avoidance of using toxic organic solvents. This system prolongs the residence time of the dose form at the site of application and facilitates an intimate contact of the dose form with the underlying mucosal surface, and thus contributes to improved and/or better therapeutic performance of the VRZ.…”

Emerging Applications of Drug Delivery Systems in Oral Infectious Diseases Prevention and Treatment

“…Furthermore, Rençber et al developed chitosan-nanoparticles containing fluconazole for the local treatment of oral candidiasis. The in vivo and in vitro test showed this DDS had the antifungal efficacy and successfully treated the infection with local administration once a day [52].…”

“…Application Oral Diseases Composition micro/nano particles micro/nano sphere dental caries [31,35] periodontitis [38] implant coating [50,51] oral candidiasis [52] PLGA, PDLLA, PEG and biopolymers like lipid, chitosan, pectin, and alginate nanofiber periodontitis [19] oral candidiasis [53] implant coating [43] nano capsule dental resin modification [42] hydrogel dental caries [54] periodontitis [55,56] oral candidiasis [57] Hydrophilic groups such as -OH, -CONH-, -CONH2dendrimer dental caries [58] PAMAM, poly(aryl ether) Figure 1. Examples of the structures of different kinds of carriers.…”

pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms

“…This was because the ionized carboxyl group on poly(g-glutamic acid) tended to protonate at lower pH, while the quaternized amine groups on chitosan became deprotonated at pH above 6.5. Insulin (Li et al, 2006(Li et al, , 2007Jelvehgari et al, 2010;Chen et al, 2016), DNA (Momenzadeh et al, 2015), Psoralidin (Yin et al, 2016), Fluconazole (Rencber et al, 2016) On the other hand, it is not an absolute requirement for cross-linker and homogenizer as the NPs can be prepared from two oppositely charged polymers, which provides a mild procedure to prevent drug (e.g. protein) denaturation (Jelvehgari et al, 2010), and improves oral absorption, especially the absorption at specific region, such as the colon.…”