A polymeric controlled drug delivery device for peptides based on a surface desorption/diffusion mechanism.

Abstract

Further investigations of the mechanisms underlying continuous peptide delivery from a newly developed Accurel polypropylene/collodion device are described. This module was prepared by lumen-loading an aqueous peptide solution into a piece of microporous Accurel polypropylene tubing which was subsequently end-sealed and encapsulated by a collodion membrane. By using vasopressin (VP) as a 'model' peptide, various aspects of the known semi-reversible protein/polymer surface interaction are shown to be present for VP and polypropylene i.e. prominent adsorption on the large surface area, which follows a bimodal adsorption isotherm, but with very limited desorption, and which can be enhanced by exchange with other proteins. Based on these findings as well as the observed steady state levels of VP on 24 h immersions in a small fixed volume, the previously proposed mechanism of pseudo-zero-order release could be evaluated further: the adsorbed peptide molecules function as a stock of near-constant activity, since desorption is rather limited, and as long as rapid exchange of bound peptide by external proteins can be prevented by a sufficiently thick (greater than 60 micron) collodion membrane, a slow long-term diffusion process will take place. Under 'infinite sink' conditions, the devices gave linear cumulative release curves for weeks. The present module is a novelty among the known membrane-controlled drug-delivery reservoir systems, since it has been loaded by an unsaturated drug solution and because the encapsulating membrane is not the sole release-rate-controlling factor.