Oral Drug Delivery
Oral drug delivery is the most convenient route of administration for the patient but for many compounds the harsh environment of gastrointestinal tract as well as the tight intestinal wall pose great drug delivery challenges.
In SweDeliver we focus on challenges within oral delivery of biologics and colonic drug delivery strategies. Emphasis is put on mechanistic understanding and new in silico and in vitro models to better design advanced drug delivery systems fulfilling the requirements for absorption of macromolecules from the small intestine and small molecules from the colon.
Our oral work package draws on the strong track record within in silico modelling and simulation, and in vitro assay development within the drug delivery and molecular pharmaceutics groups at Uppsala University.
ENABLING ABSORPTION AFTER ORAL ADMINISTRATION OF BIOLOGICS
In this project new in silico, in vitro and in vivo models are designed to explore interactions between macromolecules and common excipients used to increase the bioavailability after oral administration. Focus is on the role of physiological conditions on the erratic absorption and large inter-individual variability typically observed for biologics.
Primarily peptide-based drug molecules and transient permeability enhancers are studied and will be validated with clinical data. The models will be challenged with compounds provided from industrial partners to evaluate their general applicability to biologics also outside the peptide space, including e.g. oligonucleotides and smaller proteins.
MODIFIED RELEASE FORMULATIONS ENABLING COLONIC ABSORPTION OF POORLY SOLUBLES
A large fraction of compounds under development are poorly soluble with dissolution rate limited absorption and as a consequence such compounds display low or erratic bioavailability. While modified release formulations have been successfully designed for highly soluble compounds to be release in and absorbed from in the colon, these systems have been proven demanding to design for poorly solubles. In part this is attributed to the limited fluid available in the colon, but also other properties, such as the thickness and structure of mucus, the peristalsis in the colon and the role of the microbiome are influencing the absorption profile from colon.
To date we are still missing in vitro models that are in vivo predictive for release and absorption from this part of the intestine. This project aims at developing physiologically relevant in silico and in vitro models based on mechanistic studies in vivo; models that will improve our understanding of how to design successful dosage forms for efficient colonic release and absorption.