Formulation and evaluation of novel mucoadhesive drug delivery systems against oral buccal infectious diseases

Abstract

newline The active compound against Candida albicans, Porphyromonas gingivalis, newlineFusobacterium nucleatum, Prevotella intermedia, Provetella oralis, and Prevotella buccae newlinewas isolated from the plant Mollugo pentaphylla Linn. The isolate was identified as newlinestigmasterol based on FTIR, DSC, NMR and Mass spectral analysis. The isolated newlinestigmasterol reproduced paramount antifungal activity against Candida albicans at 100 newlineµg/mL concentration. The in-vivo study revealed that the viable fungal cell count of the newlineCandida albicans infected tongue homogenates decreased significantly after 21 days of newlinetreatment with isolated stigmasterol and histopathological study also narrated the recovery newlineof papillae, reorganization of basal cell layer and newly formed papillae after 21 to 28 newlinedays treatment. newlineThe plant isolate was encapsulated in glutaraldehyde cross linked chitosan newlinemicrospheres. The compatibility study of isolated compound with chitosan was performed newlineby FTIR and DSC study. The fabricated plant isolate encapsulated microspheres in newlinevarying concentration of chitosan and span 80 were characterized for surface morphology, newlineloading efficacy and entrapment efficacy in order to optimize the best encapsulated isolate newlinein microspheres. The optimized microspheres were taken for crystallinity study by XRD newlineand DSC in the interest of determination of the % crystallinity of the isolate encapsulated newlinein fabricated optimized microspheres. The activation energy of permeation, partition and newlinediffusion of stigmasterol from the optimized microspheres were valued to comprehend the newlinepermeation kinetic in increasing temperature. At the site of application, the formulation newlinerepresenting minimum activation energy exhibited the elevated stigmasterol permeation newlinethreshold. The effectiveness of the encapsulation and the capacity of the mucoadhesive newlinewas assumed to be proportional to the polymer-emulsifier proportion. The in-vitro release newlineanalysis narrated the direction of release of stigmasterol from formulated crafted newlinemicrospheres to be anomalous or non-fickian, which is the consequence of both diffusion newlineand erosion regulated release. The in-vivo study showed significant anti-oral candidiasis newlineaction during 21-28 days of treatment. newlinex newlineThe placebo thermoreversible gels were prepared by cold mechanical method newlineusing varying concentration of Poloxamer 407 with Carbopol 940, Carbopol 934, HPMC newlineK4M, HPMC K100M and Chitosan. The placebo bucoadhesive thermoreversible gels were newlineoptimized depending on the gelation temperature of the formulations ranged between 25- newline37oC and isolated stigmasterol of required quantity was loaded to the optimized placebo newlinebucoadhesive thermoreversible gels composition. The Sol-Gel microstate transformation newlineof the prepared stigmasterol loaded bucoadhesive thermoreversible gels were confirmed by newlineincreasing entropy of the increasing viscosity in increasing temperatures. The in-vitro newlinerelease of stigmasterol from the prepared thermoreversible gels, the formulation contained newline19% w/v of Poloxamer 407 - 0.45% w/v of chitosan and 0.01% w/v of isolated newlinestigmasterol with other excipients showed 99.063 ± 1.999% cumulative amount of isolated newlinestigmasterolrelease in 480 min which was found to be highest among the all formulations newlineand showed to follow Korsmeyers-Peppas model of release mechanism in non-fickian newlinemanner. The ex-vivo permeation of stigmasterol from the formulation contained newlinePoloxamer 407 with bucoadhesive chitosan polymer was found to be the best. The in-vivo newlinestudy with different statistical approach showed significant anti-oral candidiasis action newlineduring 21-28 days of treatment. newlineThe in-silico docking approach predicted strong negative binding energy of newlinestigmasterol with selective pathogen proteins demonstrated an in-visual perception for newlineanti-microbial efficacy. newline