Effect of Food Status on the Gastrointestinal Transit of Amphotericin B-Containing Solid Lipid Nanoparticles in Rats

Abstract

Abstract. Amphotericin B (AmB) is poorly absorbed from the gastrointestinal tract. Recent studies have suggested enhanced drug absorption from solid lipid nanoparticles (SLN). Little is known of the fate of AmB absorption within the gastrointestinal tract, and no gastrointestinal transit study has yet been performed on AmB-containing nano-formulations. We aimed to investigate the effect of food on the gastrointestinal transit properties of an AmB-containing SLN in rats. Three SLNs containing AmB, paracetamol, or sulfasalazine were formulated using cocoa butter and beeswax as lipid matrices and simultaneously administered orally to Sprague-Dawley rats. Paracetamol and sulfapyridine were used as marker drugs for estimating gastric emptying and cecal arrival, respectively. The pharmacokinetic data generated for paracetamol and sulfapyridine were used in estimating the absorption of the AmB SLNs in the small and large intestines, respectively. A delayed rate of AmB absorption was observed in the fed state; however, the extent of absorption was not affected by food. Specifically, the percentages of AmB absorption during the fasted state in the stomach, small intestine, and colon were not significantly different from absorption within the respective regions in the fed state. In both states, however, absorption was highest in the colon and appeared to be a combination of absorption from the small intestine plus absorption proper within the colon. The study suggests that AmB SLN, irrespective of food status, is slowly but predominantly taken up by the lymph, making the small intestine the most favorable site for the delivery of the AmB SLNs.

Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy

“…The obtained data revealed that rate absorption of AmB from SLNs decreased with the presence of food, contrary to the extent of absorption that remained practically unchanged [240]. Regardless of the food status, these results suggested that amphotericin SLNs could be mainly taken up by the lymph, with the small intestine as the best delivery site for the prepared nanoformulation [240].…”

“…The improved bioavailability observed with oral delivery of SLNs could be related to an increase of residence time within the gut due to the interactions of lipids on the surface of NPs with the epithelial membranes [160]. Gastric and intestinal enzymes are prone to degrade lipid-based delivery systems and absorption can be enhanced in the course of the digestion of triglycerides from SLNs by pancreatic lipase [239,240]. Stability, drug release behavior, and in vivo performance of SLNs are also related to the location of the drug in the lipid matrix.…”

“…The results obtained by Amekyeh et al indicated a possible aggregation of SLNs in the stomach with particles showing an optimal size (below 350 nm) and surface charge for absorption in the small intestine [241]. Food status may affect the bioavailability of SLNs containing AmB, resulting from changes in the drug dissolution prior to absorption, changes in GI residence time of formulation or alterations in drug membrane permeability, and absorption [240]. The effect of food on the GIT of AmB-loaded SLNs was studied in rats, using paracetamol and sulfapyridine as marker drugs to evaluate gastric emptying and cecal arriving, respectively [240,242].…”

“…Food status may affect the bioavailability of SLNs containing AmB, resulting from changes in the drug dissolution prior to absorption, changes in GI residence time of formulation or alterations in drug membrane permeability, and absorption [240]. The effect of food on the GIT of AmB-loaded SLNs was studied in rats, using paracetamol and sulfapyridine as marker drugs to evaluate gastric emptying and cecal arriving, respectively [240,242]. The obtained data revealed that rate absorption of AmB from SLNs decreased with the presence of food, contrary to the extent of absorption that remained practically unchanged [240].…”

“…The effect of food on the GIT of AmB-loaded SLNs was studied in rats, using paracetamol and sulfapyridine as marker drugs to evaluate gastric emptying and cecal arriving, respectively [240,242]. The obtained data revealed that rate absorption of AmB from SLNs decreased with the presence of food, contrary to the extent of absorption that remained practically unchanged [240]. Regardless of the food status, these results suggested that amphotericin SLNs could be mainly taken up by the lymph, with the small intestine as the best delivery site for the prepared nanoformulation [240].…”