Controlled long-term release of small peptide hormones using a new microporous polypropylene polymer: its application for vasopressin in the Brattleboro rat and potential perinatal use.
Based on drug release by microporous hollow fibers and the recent introduction of microporous polymers, a new technique was developed for controlled delivery of peptides. Small-diameter microporous polypropylene tubing, lumen-loaded with microgram quantities of vasopressin, and coated with collodion, releases vasopressin after in vitro immersion slowly (1-100 ng/d) and constantly for months. The mechanism of pseudo-zero-order delivery is based on high adsorption of vasopressin, keeping the void volume concentration of dissolved vasopressin constant, which is consequently a constant driving force of outward diffusion. The collodion coating prevents the entry of proteinaceous compounds which would result in rapid desorption of vasopressin. The present delivery module provides a lasting release for other peptides as well (lysine-vasopressin, oxytocin, alpha-melanocyte-stimulating hormone and, to a lesser extent, Met-enkephalin). The microporous polymer-collodion device is biocompatible and, loaded with vasopressin, successfully alleviates the diabetes insipidus of Brattleboro rats deficient for vasopressin. Subcutaneous implantation normalized diuresis for a period of 60 d and constant urine vasopressin excretion is observed. When the commercially available osmotic minipump is too large for implantation, the small size of the present controlled-delivery system allows peptide treatment of young and immature laboratory rats, even if located in utero.
D000818:Animals; D003692:Delayed-Action Preparations; D004231:Diuresis / Q000187:drug effects; D004343:Drug Implants; D005260:Female; D007457:Iodine Radioisotopes; D011108:Polymers; D011126:Polypropylenes; D011247:Pregnancy; D051381:Rats; D011910:Rats, Brattleboro; D011919:Rats, Inbred Strains; D013997:Time Factors; D014667:Vasopressins / Q000008:administration & dosage* / Q000097:blood / Q000172:deficiency
D003692:Delayed-Action Preparations; D004343:Drug Implants; D007457:Iodine Radioisotopes; D011108:Polymers; D011126:Polypropylenes; D014667:Vasopressins