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• W4224239578 abstract "Besides the prominent anti fungal efficacy, amphotericin B (AmB) presents pharmaceutical challenges for clinical use requiring intravenous administration due to its intrisec properties, i.e. low water solubility and low membrane permeability. In addition, this antibiotic causes several toxic effects, making the development of a safer and oral AmB desirable to improve clinical practice. In this context, encapsulation of AmB in lipid biodegradable carriers presents a prominent pharmaceutical strategy, specially, focusing in a new administration route and in increased safety. In this context, this work aims to evaluate the intestinal transport of both isolated and encapsulated AmB employing Caco-2 monolayer as in vitro model in order to suggest a new AmB therapeutic option. Additionally, the influence of an absorption inducer (quercetin) was investigated, as well. To guarantee the protocol validity, a comprehensive LC-MS bioanalytical method was validated, as well as the AmB stability and Caco-2 monolayer integrity were investigated. During absorption experiments, after adding a known AmB amount in the apical chamber, the amount of AmB in the basolateral chamber was quantified in function of time and the absorption parameters were determined. A first set of experiments demonstrated the profile of isolated AmB transport and its apparent permeability coefficient of absorption was calculated (P app = 0.456 × 10 −6 cm s −1 ). During the comparative study, AmB from the nanoparticle sample was better absorbed than isolated AmB, as demonstrated by the 38% increase in P app (P app = 0.631 × 10 −6 cm s −1 ). Quercetin even enhanced the absorption of AmB encapsulated in 52% by increasing the P app to 0.693 × 10 −6 cm s −1 . These results suggest that the AmB delivery system based on lipid nanoparticles is a promising strategy to increase AmB oral absorption." @default.
• W4224239578 created "2022-04-26" @default.
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• W4224239578 date "2022-05-01" @default.
• W4224239578 modified "2023-10-17" @default.
• W4224239578 title "Predicting absorption of amphotericin B encapsulated in a new delivery system by an in vitro Caco-2 cell model" @default.
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• W4224239578 doi "https://doi.org/10.1016/j.jddst.2022.103345" @default.
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