Identification of multi-targeted anti-migraine potential of nystatin and development of its brain targeted chitosan nanoformulation.

The complex pathophysiology involved in migraine necessitates the drug treatment to act on several receptors simultaneously. The present investigation was an attempt to discover the unidentified anti-migraine activity of the already marketed drugs. Shared featured pharmacophore modeling was employed for this purpose on six target receptors (ß2 adrenoceptor, Dopamine D3, 5HT1B, TRPV1, iGluR5 kainate and CGRP), resulting in the generation of five shared featured pharmacophores, which were further subjected to virtual screening of the ligands obtained from Drugbank database. Molecular docking, performed on the obtained hit compounds from virtual screening, indicated nystatin to be the only active lead against the receptors iGluR5 kainate receptor (1VSO), CGRP (3N7R), ß2 adrenoceptor (3NYA) and Dopamine D3 (3PBL) with a high binding energy of -11.1, -10.9, -10.2 and -12kcal/mole respectively. The anti-migraine activity of nystatin was then adjudged by fabricating its brain targeted chitosan nanoparticles. Its brain targeting efficacy, analyzed qualitatively by confocal laser scanning microscopy, demonstrated a significant amount of drug reaching the brain. The pharmacodynamic models on Swiss male albino mice revealed significant anti-migraine activity of the nanoformulation. The present study reports for the first time the therapeutic potential of nystatin in migraine management, hence opening avenues for its future exploration.

Actividad antimicrobiana del cloruro de 2-metacriloil oxietil trimetilamonio contra Candida sp / Antimicrobial activity of [2-(methacryloyloxy)ethyl]trimethylammonium chloride against Candida spp

Antecedentes. La estomatitis protética es la forma más común de infección bucal producida por especies de Candida, siendo Candida albicans el agente etiológico más común. Diversos autores han intentado asociar agentes antifúngicos o antisépticos a los materiales de revestimiento blando o a las resinas acrílicas de las prótesis dentales, pero sin éxito. Por ello, se ha investigado un compuesto de amonio cuaternario (2-metacriloil oxietil trimetilamonio [MADQUAT]), que copolimeriza con los metacrilatos y que podría actuar como inhibidor de levaduras. Objetivos. El objetivo de este estudio fue evaluar la actividad in vitro del MADQUAT contra especies de Candida. Métodos. Se utilizaron 31 cepas de Candida para determinar la actividad antifúngica in vitro. Se determinó la concentración mínima inhibitoria (CMI) y la concentración mínima fungicida del MADQUAT, así como de la nistatina. Resultados. El MADQUAT presentó propiedades antifúngicas en las concentraciones entre 6,25 y > 100mg/ml y actividad fungicida entre 25 y > 100mg/ml. Los estudios cuantitativos de la actividad fungistática y fungicida del MADQUAT demostraron actividad fungistática contra todas las cepas de Candida albicans, Candida krusei y Candida parapsilosis, revelando actividad fungicida contra algunas cepas de otras especies. Conclusiones. El MADQUAT presenta actividad antifúngica contra Candida spp. Además, la sensibilidad a dicho compuesto es distinta entre las diferentes especies considerando los valores de la CMI y la actividad fungicida o fungistática(AU)

Background. Candida-associated denture stomatitis is the most common manifestation of oral candidal infection, caused mainly by Candida albicans. Several authors have attempted to add antifungal agents or antiseptics to denture temporary soft lining materials or to denture acrylic resins, without relevant results. Therefore, the investigation of a quaternary ammonium functionalized compound [2-(methacryloyloxy)ethyl]trimethylammonium chloride (MADQUAT), which copolymerizes with methacrylates and which could act as a fungal inhibitor, is of paramount importance. Aims. To evaluate the in vitro activity of MADQUAT against Candida species. Methods. Thirty-one Candida strains were used to determine the in vitro antifungal activity of this compound. The minimum inhibitory concentrations and minimum fungicidal concentrations of MADQUAT and nystatin were determined. Results. MADQUAT showed antifungal properties at concentrations of 6.25 to > 100mg/ml, and fungicidal activity between 25 and > 100mg/ml. The quantitative determinations of the fungistatic and fungicidal activity of MADQUAT showed fungistatic activity against all Candida albicans, Candida krusei and Candida parapsilosis strains, revealing fungicidal activity against some strains of the other species. Conclusions. MADQUAT has antifungal activity against Candida spp. Moreover, the sensitivity to this substance varies across the different species in terms of MIC values and fungicidal or fungistatic activity(AU)

Double-layered mucoadhesive tablets containing nystatin.

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.