RELEASE OF THE GRF29NH(2) ANALOG OF HUMAN GRF44NH(2) FROM A PLA/GA MATRIX

The GRF29NH2 fragment of human growth hormone releasing hormone (GHRH or GRF44NH2) is currently regarded as of interest to increase body growth by stimulation of the release of growth hormone (GH). Because this analog has a short lifetime in body fluids and because it is usually injected i.v. repeatedly, a biodegradable pellet system was selected in an attempt to apply the concept of controlled drug delivery to the administration of GRF29NH2 according to therapeutic requirements. Pellets were made by compression moulding of powdered GRF29NH2 mixed with a lactic/glycolic acid copolymer, namely PLA37.5GA25 synthesized by bulk polymerization of a feed containing 75% DL-lactide and 25% glycolide. This protocol was supposed to yield pellets releasing the oligopeptide under percolation conditions. The effects of pH and of ionic strength on the release of GRF29NH, in water were investigated in vitro. GRF29NH2 appeared unexpectedly insoluble in salt-containing neutral water and clotted the pellet porosity under static conditions. A simple device based on the use of a cotton dental tampon entrapped within a glass tube supplied with a regular flow of aqueous medium was used to show that release was achievable under dynamic conditions mimicking the situation at the administration site after s.c. injections or pellet implantations.