Co-polymerised peptide particles (CPP) I: synthesis, characterisation and in vitro studies on a novel oral nanoparticulate delivery system

Abstract A novel co-polymeric nanoparticulate drug delivery system (Co-polymerised Peptide Particles: CPP) has been developed as a carrier for the oral uptake of therapeutic peptides. The system was based on the co-polymerisation of the active peptide derivative with n-butylcyanoacrylate ( n -BCA), the resulting co-polymer being formulated as nanoparticles. The peptide luteinizing hormone releasing hormone (LHRH) was used as a model drug to investigate the viability of the approach. LHRH was covalently bound to vinylacetic acid and the resulting LHRH-vinylacetate conjugate ( 3e ) and a radiolabel ( 3c∗ ) were subsequently co-polymerised with n -BCA. The polymerisation reaction conditions were manipulated to exploit the particle-forming properties of n -BCA, so that the co-polymer was prepared as particles of average diameter 100 nm, containing LHRH molecules covalently bound as constituents of the oligomeric chains which formed the particles, rather than physically entrapped or adsorbed. The vinylacetic acid functions as a ‘linking acid’, allowing the formation of a polymerizable derivative of the peptide; also, the stability of the covalent bond between LHRH and vinylacetic acid ensures that the LHRH remains entrapped, and therefore protected, within the carrier in vivo. The co-polymeric particles were found to be stable in vitro when incubated over a 3 h period in gut luminal contents and mucosal scrapings. Their stability was also demonstrated in fetal calf serum and rat serum. In vitro transport studies using the Caco-2 cell line suggested that absorption in vivo was possible.