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Research Call

DAFM Reference

Lead(Collaborating)Institution

DAFM Award

DAFM National Call 2011 11F042 DIT (UCD) €477,815

Project Title:

Translation of pharmaceutical drug delivery to nutraceutical delivery using in-vitro and in-vivo techniques.

Project Coordinator:

Dr Jesus Frias

Project Abstract

Meat and milk derived peptides have recently been shown to exhibit antihypertensive effects leading to a growing commercial interest in their potential health benefits. The bioactive peptides Ile-Pro-Pro (IPP) and Leu-Lys-Pro (LKP) could be taken orally to treat hypertension however their bioavailability is limited because of the stomach¿s acidic pH, metabolism by luminal, brush border and cytosolic peptidases, and poor permeability across the intestinal epithelium. Establishing an oral delivery system for IPP and LKP would be significant for these peptides and other naturally-occurring bioactive peptides. One solution is to formulate the peptide into a nanoparticle drug delivery system and this will be the focus of this research project. The nanoparticles will be based on the formation of polyelectrolyte complexes using the stabiliser chitosan and alginate. Key considerations for oral delivery are 1. the nanoparticle must be biocompatible and biodegradable using food-grade materials, 2. degradation products must also be biocompatible and non-toxic; 3. high drug loading capacity and 4. sustained controlled release of the drug. [1]. The physico-chemical characteristics of the formulations will be assessed. The team will perform controlled release studies using standard dissolution tests; stability analysis using gastrointestinal enzymes; cytotoxicity studies using intestinal and liver cell models and blood (target site). In-vitro transport studies using epithelial monolayer models simulating the intestine will give an initial indication of the transport mechanisms, and possible inhibitions or active efflux transport mechanisms. Ex-vivo transport studies using rat intestinal tissue Ussing chambers and oral administration and analysis using the spontaneously hypertensive rat model will offer proof of concept.

Final Report:

Not available yet.