methylcellulose and Candidiasis--Oral

We examined the effects of spices and herbs on Candida albicans to develop therapeutic tools against oral diseases such as oral candidiasis. C. albicans, a dimorphic fungus, is a component of the healthy human microbial flora. However, the excessive overgrowth of C. albicans causes oral candidiasis, and the symptoms, accompanied by severe inflammation, reduce the quality of life of elderly people. We found that spices such as clove (Syzygium aromaticum) and cassia (Cinnamomum aromaticum) exhibit inhibitory activity against Candida mycelial growth and show therapeutic efficacy in a murine oral candidiasis model. Our studies also demonstrated that the inhibitory activity of cinnamaldehyde was strengthened in parallel with a prolonged treatment time. Furthermore, when cinnamaldehyde in combination with methylcellulose was administered to the model mice, the therapeutic effect was potentiated. Here, we summarize up-to-date findings on how to use spices and herbs on a daily basis to improve or prevent oral problems such as oral candidiasis with the presentation of our recent data.

Topics: Acrolein; Animals; Candida albicans; Candidiasis, Oral; Cinnamomum aromaticum; Disease Models, Animal; Drug Resistance, Fungal; Humans; Methylcellulose; Mice; Plant Extracts; Plants, Medicinal; Spices; Syzygium

Oral candidiasis (OC), caused by the fungal pathogen Candida albicans, is the most common opportunistic infection in HIV(+) individuals and other immunocompromised populations. The dramatic increase in resistance to common antifungals has emphasized the importance of identifying unconventional therapeutic options. Antimicrobial peptides have emerged as promising candidates for therapeutic intervention due to their broad antimicrobial properties and lack of toxicity. Histatin-5 (Hst-5) specifically has exhibited potent anticandidal activity indicating its potential as an antifungal agent. To that end, the goal of this study was to design a biocompatible hydrogel delivery system for Hst-5 application. The bioadhesive hydroxypropyl methylcellulose (HPMC) hydrogel formulation was developed for topical oral application against OC. The new formulation was evaluated in vitro for gel viscosity, Hst-5 release rate from the gel, and killing potency and, more importantly, was tested in vivo in our mouse model of OC. The findings demonstrated a controlled sustained release of Hst-5 from the polymer and rapid killing ability. Based on viable C. albicans counts recovered from tongues of treated and untreated mice, three daily applications of the formulation beginning 1 day postinfection with C. albicans were effective in protection against development of OC. Interestingly, in some cases, Hst-5 was able to clear existing lesions as well as associated tissue inflammation. These findings were confirmed by histopathology analysis of tongue tissue. Coupled with the lack of toxicity as well as anti-inflammatory and wound-healing properties of Hst-5, the findings from this study support the progression and commercial feasibility of using this compound as a novel therapeutic agent.

Topics: Animals; Antifungal Agents; Biocompatible Materials; Candida albicans; Candidiasis, Oral; Disease Models, Animal; Drug Carriers; Drug Resistance, Fungal; Female; Histatins; Hydrogel, Polyethylene Glycol Dimethacrylate; Methylcellulose; Mice; Mice, Inbred C57BL; Microscopy, Electron, Scanning; Tongue

We examined the therapeutic effects of cinnamaldehyde and the potentiation of those effects with cassia and cinnamaldehyde when combined with the food additive methylcellulose against murine oral candidiasis. When 19.5mg/ml of cinnamaldehyde was administered in the oral cavity of Candida infected mice, the oral symptoms were improved. Furthermore, when either a cassia or a cinnamaldehyde preparation in combination with methylcellulose was administered to oral candidiasis-inflicted mice, the therapeutic effects of cassia or cinnamaldehyde potentiated. Methylcellulose itself did not affect the oral symptoms or the viable number of C. albicans cells. GC/MS analysis showed that the dose of cinnamaldehyde remaining in the tongue tissue of mice treated with the cinnamaldehyde-methylcellulose mixture was higher than that in mice administered cinnamaldehyde alone, and also showed that cinnamaldehyde was not detected in the blood of any of the tested mice. These findings suggested that the combination of cassia or cinnamaldehyde and methylcellulose may be a useful prophylactic or therapeutic tool against oral candidiasis.

Topics: Acrolein; Administration, Oral; Animals; Candidiasis, Oral; Cassia; Disease Models, Animal; Drug Synergism; Female; Methylcellulose; Mice; Mice, Inbred ICR; Plant Preparations

Fluconazole mucoadhesive buccal films were prepared using film forming polymers namely; hydroxypropyl methyl cellulose (HPMC), hydroxyethyl cellulose (HEC), chitosan, Eudragit and sodium alginate (SALG) either alone or in combination with bioadhesive polymers. The bioadhesive polymers studied were sodium carboxymethyl cellulose (SCMC), Carbopol 974P, and polycarbophil (AA-A). The prepared films were characterized by means of film thickness, surface pH, swelling capacity, in vitro adhesion, in vivo residence time, in vitro drug release and in vivo drug release to determine the amount of drug release from selected film formulae using microbiological assay and HPLC. Optimum release behavior, convenient bioadhesion, acceptable elasticity were exhibited by film containing 2% HPMC and 1% SCMC (fresh or stored for 6 months). Determination of the amount of drug released in saliva after application of the selected fluconazole films confirmed the ability of the film to deliver the drug over a period of approximately 300 minutes and to reduce side effects and possibility of drug interaction encountered during systemic therapy of fluconazole, which would be beneficial in the case of oral candidiasis.

Topics: Acrylic Resins; Adhesiveness; Adult; Alginates; Antifungal Agents; Candidiasis, Oral; Carboxymethylcellulose Sodium; Cheek; Female; Fluconazole; Glucuronic Acid; Hexuronic Acids; Humans; Hypromellose Derivatives; Male; Methylcellulose; Polyvinyls; Solubility

The objective of this work was to design a mucoadhesive tablet with a potential use in the treatment of oral candidosis. A 2-layered tablet containing nystatin was formulated. Lactose CD (direct compression), carbomer (CB), and hydroxypropylmethylcellulose (HPMC) were used as excipients. Tablets were obtained through direct compression. Properties such as in vitro mucoadhesion, water uptake, front movements, and drug release were evaluated. The immediate release layer was made of lactose CD (100 mg) and nystatin (30 mg). The CB:HPMC 9:1 mixture showed the best mucoadhesion properties and was selected as excipient for the mucoadhesive polymeric layer (200 mg). The incorporation of nystatin (33.3 mg) in this layer affected the water uptake, which, in turn, modified the erosion front behavior. Nystatin showed a first-order release. The polymeric layer presented an anomalous kinetic (n = 0.82) when this layer was individually evaluated. The mucoadhesive tablet formulated in this work releases nystatin quickly from the lactose layer and then in a sustained way, during approximately 6 hours, from the polymeric layer. The mixture CB:HPMC 9:1 showed good in vitro mucoadhesion. A swelling-diffusion process modulates the release of nystatin from this layer. A non-Fickian (anomalous) kinetic was observed.

Topics: Acrylic Resins; Adhesiveness; Administration, Oral; Antifungal Agents; Candidiasis, Oral; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diffusion; Drug Compounding; Drug Design; Drug Evaluation, Preclinical; Hypromellose Derivatives; Lactose; Methylcellulose; Nystatin; Solubility; Tablets; Time Factors; Water