pH-Sensitive nanoparticles containing 5-fluorouracil and leucovorin as an improved anti-cancer option for colon cancer

Parenteral administration of chemotherapeutic drugs, 5-fluorouracil (5-FU) and leucovorin (LV), is commonly used to treat large bowel carcinomas such as colon cancer (CC) and colorectal carcinoma (CRC). Our study aims to design a novel nanoparticulate drug-delivery vehicle for oral use capable of colon-specific release. A modified double-emulsion solvent evaporation method was used in the preparation of pH-responsive Eudargit S100 polymeric nanoparticles, loaded with 5-FU/LV combination (5-FU/LV-loaded Eudargit S100 NPs). Our optimized drug-loaded NP showed a pH-responsive drug release and exhibited significantly more cytotoxic actions in cancer-cell lines than free drugs. These findings open the way for conducting clinical trials for colon malignancies treated with nanoparticles

pH-sensitive nanoparticles containing 5-fluorouracil and leucovorin as an improved anti-cancer option for colon cancer.

Parenteral administration of chemotherapeutic drugs, 5-fluorouracil (5-FU) and leucovorin (LV), is commonly used to treat large bowel carcinomas such as colon cancer (CC) and colorectal carcinoma (CRC). Our study aims to design a novel nanoparticulate drug-delivery vehicle for oral use capable of colon-specific release. A modified double-emulsion solvent evaporation method was used in the preparation of pH-responsive Eudargit S100 polymeric nanoparticles, loaded with 5-FU/LV combination (5-FU/LV-loaded Eudargit S100 NPs). Our optimized drug-loaded NP showed a pH-responsive drug release and exhibited significantly more cytotoxic actions in cancer-cell lines than free drugs. These findings open the way for conducting clinical trials for colon malignancies treated with nanoparticles

Bioadhesive behaviors of HPMC E5: comparative analysis of various techniques, histological and human radiological evidence

Abstract Enhancing drug residence duration within the stomach offers distinct advantages for both localized and systemic effects. Numerous strategies have been proposed to extend drug residence time, with mucoadhesive polymers being a notable avenue. In this context, hydroxypropyl methylcellulose E5 has been employed as both a binding agent for granulating contrast metal powder and a mucoadhesive polymer, spanning various concentrations. The in vitro bioadhesion strength of the formulated tablets was gauged against the stomach lining of rabbits, for the quantification of bioadhesive forces. The temporal aspect of bioadhesion was evaluated through two approaches: one centered on gastric fluid dynamics and another proffered by the researchers, focusing on gastric wall kinetics. The results divulged a decline in bioadhesion force concomitant with high polymer concentrations. Histological examination of stained stomach sections revealed mucosal perturbations within the rabbit stomach. These disruptions exhibited an escalating trend in conjunction with elevated polymer concentrations, culminating in extensive disturbance at a 7.5% polymer concentration. The outcomes unveiled a direct relationship between polymer concentration increments and extended contact time. Subsequent radiological tracking of contrast metal behavior within a mature human stomach indicated a residence time of 6 h due to the entrapment of displaced components at disparate locations

Miconazole-Urea in a Buccal Film as a New Trend for Treatment of Resistant Mouth Fungal White Patches

A growing concern about Candida albicans is the emergence of high incidence of resistance against antifungal agents, which requires searching for new medications or improving the response to the existing members. The objective of this work was to evaluate the effectiveness of the miconazole in the absence and presence of urea, as a penetration enhancer, against C. albicans. In addition to, formulating both of them in a polymer film to be used topically for treatment of mouth fungal white patches caused by C. albicans. A synergistic effect was recorded between this imidazole and urea against the test strain. Miconazole MIC (32 mg/L) was dramatically reduced to 0.0625 mg/L following combination with urea. Transmission electron microscopy explained the mechanisms of action mediated by the test agents. Minimal fungicidal dose of miconazole combined with urea showed early apoptotic cells with condensed chromatin and small blebs. Cytoplasmic leakage and necrosis in some cells was observed at high fungicidal dose. Buccal bioadhesive films were prepared using increasing values of the drug MIC and urea. The physicochemical characters of the prepared films including; film weight, thickness, swelling index, drug content, folding endurance, surface pH, bioadhesion force and time and drug release kinetics, were studied. Microbiological evaluation of all prepared films showed an increase in the inhibition zone diameters for films containing increasing concentrations of both miconazole and urea in a concentration-dependent manner (30–40 mm) compared to miconazole alone (18 mm). Based on our results, the prepared films are promising for buccal administration of miconazole/urea showing synergistic effect for treatment of C. albicans infection

Minimal underlying data.

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CONSORT 2010 checklist of information to include when reporting a randomised trial*.

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List of interventions.

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List of participating sites and ethics committee approvals.

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Data measures definitions.

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Characteristics of participating sites.

IQR: interquartile range. (PDF)</p