Mucoadhesive assessment of different antifungal nanoformulations

Abstract

Oral candidiasis is an important opportunistic fungal infection and polyenes and azoles are still the most used antifungal agents. However, the oral absorption resulting from most available treatments is generally poor and, consequently, a very high frequency of administrations of antifungal agents is strongly required. Therefore, the major challenge is to improve the retention of the antifungal agents in buccal mucosa, and the encapsulation into mucoadhesive systems may be considered as a possible strategy to achieve this objective. Three types of mucoadhesive polymeric nanoparticles (polylactic acid (PLA), polylactic-co-glycolic acid (PLGA) and alginate) were prepared using nystatin as model drug. The drug-loaded nanoparticles were then included in toothpaste, oral gel and oral films, respectively. The results demonstrated that the loaded nanoparticles were successfully produced, presenting a mean size between 300-900 nm and with a negative surface charge. Also, the determination of the encapsulation efficiency of all nanoparticles showed values above 70%. In terms of the in vitro mucoadhesion, the best formulation was the oral film loaded with the PLGA nanoparticles followed by the oral gel with PLA nanoparticles and thirdly the toothpaste with alginate nanoparticles. This was confirmed in an in vitro rinsing model with mucus producing HT29-MTX cells, where the percentage of nystatin retained to the cells after 40 min of simulated saliva flow was between 10-27% when formulations were used and only 4% for free nystatin. Further studies will include in vivo testing using animal models.

Novel and revisited approaches in nanoparticle systems for buccal drug delivery

“…of Candida albicans over one year when compared to nystatin alone. This study was the base to another study in which PLGA, polylactic acid (PLA) and alginate nanoparticles were able to encapsulate nystatin [133]. All the polymers were bioadhesive and stable over 6 months.…”

“…The adhesive capacity of the alginate, PLGA and PLA nanoparticles was assessed in an in vitro J o u r n a l P r e -p r o o f rinsing model with mucus producing HT29-MTX cells. The percentage of nystatin retained in the cells after 40 min of simulated saliva flow was between 10-27%, when nanoparticles were used and only 4% for free nystatin [133]. The cytotoxicity assays were performed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using TR146 human buccal cancer cells as in vitro model of human buccal mucosa [134].…”

Therapeutic tools for oral candidiasis: Current and new antifungal drugs

“…Antifungal formulations are marketed as oral suspensions, tablets, pastilles, gels, mucoadhesive tablets, toothpastes, etc. for facilitating their therapeutic action that are very effective in curing most oral candidiasis in a few weeks (15,17,29). Although systemic azoles and echinocandins, with better tastes and less gastrointestinal adverse reactions, have provided new clinical options, topical therapy using nystatin (polyene) and miconazole (azole) are still the main recommended treatments for oral candidiasis due to its high efficacy, low cost, and less side effects, especially in low-income countries.…”

Nanoparticles in Dentistry: A Comprehensive Review

“…Treating oral candidiasis and denture stomatitis can be challenging, as it involves the improvement of oral and/or denture hygiene, relining or replacing the prostheses, avoiding overnight use of dentures, and the topical and/or systemic administration of antifungal drugs [174]. However, the effectiveness of treatment can be compromised by the cost of medication [176], its unpleasant taste, toxicity, and possible side effects, including nausea, mouth irritation, vomiting, and diarrhea [173,174], poor oral absorption [177], drug resistance [176], and the cleansing effect of saliva [173]. Nanotechnology has been proposed to overcome such obstacles, given that unconventional antimicrobial agents hold great potential in the treatment of infectious diseases [178].…”

“…Mucoadhesives, gels, toothpastes, buccal tablets, and buccal films have been proposed as treatments for oral candidiasis. Such formulations were developed with NPs for improved local delivery of drugs like miconazole [176,[188][189][190], nystatin [173,177], amphotericin B [191], and fluconazole [192], or plant-derived products, such as stigmasterol [193] or Glycyrrhiza glabra L. extract [194]. Some of these formulations presented enhanced antifungal activity, reduced cytotoxicity, faster drug release rate, improved dissolution rate, and better prolonged release than marketed products or the non-loaded drug [176,[188][189][190][191], while others, despite not being compared to commercialized products, have shown promising results [173,177,[192][193][194].…”