Oral absorption studies of lipid-polylysine conjugates of thyrotropin releasing hormone (TRH) and luteinizing hormone releasing hormone (LHRH)

The lipoamino acids and their oligomers provide an excellent means of enhancing peptide lipophilicity and also helping to increase the stability of the peptide and protect it from enzymatic degradation. Thyrotropin releasing hormone (TRH) and luteinizing hormone releasing hormone (LHRH) were extended on the N-terminal with one and two lipoamino acids and labelled with the H-3-acetyl group. TRH and LHRH conjugates were also prepared where the compounds were extended with two lipoamino acids, a polylysine unit and the N-terminal labelled with the H-3-acetyl group. The higher lipophilicity resulted in a higher Caco-2 cell association and also a higher rate of oral uptake. The addition of the polylysine system increased the water solubility, as well as the oral uptake of the conjugates. The conjugates developed have been absorbed and detected after oral administration and appear to be stable for a considerable time in vivo.