Colon specific sustained drug release by hydrodynamic sorting
A problem presented at the UK MMSG Keele 2012.
- Presented by:
- (Food Structure and Health, Institute of Food Research)
Problem Description
The site-targeted delivery of drugs to the terminal ileum and large bowel has implications in a number of therapeutic areas including the topical treatment of colonic disorders such as Crohn's disease, ulcerative colitis, constipation, colorectal cancer, spastic colon and irritable bowel syndrome.
We aim to evaluate the feasibility of an entirely new temporal control mechanism for multiple dose units: hydrodynamic sorting in the gastro-intestinal tract (GIT) based on particle size, shape or mass density. Unlike conventional drug delivery systems, the fundamental physical mechanism hinges on the mechanical interaction between the drug carrying object and the GIT fluid flow field.
The key questions for the study group to address are:
- Can hydrodynamic interactions provide a tunable mechanism for spatio- temporal of MDU delivery vehicles in the GIT?
- If yes, then how sensitive is the downstream particle distribution to details of the flow field? (e.g., what distinguishes the sorting characteristics of Poiseuille flow and intermittent plug flow, say?)
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Study Group Report
A first attempt at understanding hydrodynamic sorting of particles travelling through the GIT should focus on the essential distinguishing characteristics of the two intestinal motility mechanisms, segmentation and peristalsis. Our strategy has considered each mechanism in isolation and in concert to arrive at three different models:
- Model I appeals to the theory of Taylor dispersion to account for mixing driven by segmentation motions;
- Model II utilises an analytic flow field consistent with peristaltic driving motion to simply advect a scalar solute concentration field in a finite element numerical scheme;
- Model III relaxes the assumption of a continuous solute concentration and considers the possibility of appropriating classical Brownian dynamics simulation technology to combine both the effects of stochastic dispersion and deterministic convection using ideas from Models I and II.
How best to engage these mechanisms in practical drug delivery remains very much an open question, however. Only Model III recognises the discrete particle nature of the MDU contents and the very preliminary stage of development achieved at MMSG12 precludes an unequivocal explanation relating the individual particle properties (size, shape, density, etc.) to de-mixing of an initially localised distribution. Certainly there is plenty of scope for additional work in this area.