Abstract
The oral route is the most preferable one when it comes to drug administration. Different animal models have been used to characterize the fate of potential medicines upon oral delivery but fail to clarify specific events occurring at localized sites of the gastrointestinal tract, particularly at the small intestine. We developed a new mouse intra-intestinal infusion model that enabled the direct administration of substances (such as drugs or nanoparticle drug carriers) in the small intestine through an implanted catheter, which can be maintained for prolonged periods of time. The location of catheter insertion can be previously determined as more proximal or distal, allowing to test specific portions of the intestine. Since the model is presumably able to maintain normal physiological characteristics, namely the mucus coating of the intestinal wall, it allowed studying the distribution of different nanoparticles upon localized intra-intestinal administration. The hereby proposed mouse model has the potential to be useful in other types of studies, namely in clarifying localized processes occurring at specific sites of the intestine.
Highlights
The oral intake of medicines is the main form of drug delivery, making the gastrointestinal tract (GIT) the most important barrier before systemic drug exposure occurs (Mrsny, 2012)
Different events occurring between oral intake and intestinal absorption may be determinant in defining the fate of drugs, namely those involved in the release and local distribution of a pharmaceutical dosage form or delivery system (Koziolek et al, 2016)
In this article we describe a new mouse model for direct intra-intestinal infusion in order to administer, in a precise way, drugs or delivery systems into specific regions
Summary
The oral intake of medicines is the main form of drug delivery, making the gastrointestinal tract (GIT) the most important barrier before systemic drug exposure occurs (Mrsny, 2012). Normal physiological mechanisms (e.g., gastric digestion and emptying, intestinal peristalsis) and barriers (e.g., the mucus covering the mucosal wall, intestinal villi) play key roles in defining localized events at different points of the GIT (McConnell et al, 2008; Mudie et al, 2010). Understanding how these can affect the behavior of drug and/or dosage forms or delivery systems is essential in identifying critical steps that may preclude drug absorption at the intestinal epithelium. This introduces significant bias as to the appropriate measures required for enhancing the bioavailability of molecules of interest and may impair fast and reliable product development, with financial losses thereof
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