CO-POLYMERIZED PEPTIDE PARTICLES (CPP) .1. SYNTHESIS, CHARACTERIZATION AND IN-VITRO STUDIES ON A NOVEL ORAL NANOPARTICULATE DELIVERY SYSTEM

A novel co-polymeric nanoparticulate drug delivery system (Co-polymeri sed Peptide Particles: CPP) has been developed as a carrier for the or al uptake of therapeutic peptides. The system was based on the co-poly merisation of the active peptide derivative with n-butylcyanoacrylate (n-BCA), the resulting co-polymer being formulated as nanoparticles. T he peptide luteinizing hormone releasing hormone (LHRH) was used as a model drug to investigate the viability of the approach. LHRH was cova lently bound to vinylacetic acid and the resulting LHRH-vinylacetate c onjugate (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-poly mer was prepared as particles of average diameter 100 nm, containing L HRH molecules covalently bound as constituents of the oligomeric chain s which formed the particles, rather than physically entrapped or adso rbed. The vinylacetic acid functions as a 'linking acid', allowing the formation of a polymerizable derivative of the peptide; also, the sta bility of the covalent bond between LHRH and vinylacetic acid ensures that the LHRH remains entrapped, and therefore protected, within the c arrier 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 muc osal scrapings. Their stability was also demonstrated in fetal calf se rum and rat serum. In vitro transport studies using the Caco-2 cell li ne suggested that absorption in vivo was possible.