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 stabi lity of the peptide and protect it from enzymatic degradation. Thyrotr opin releasing hormone (TRH) and luteinizing hormone releasing hormone (LHRH) were extended on the N-terminal with one and two lipoamino aci ds and labelled with the H-3-acetyl group. TRH and LHRH conjugates wer e also prepared where the compounds were extended with two lipoamino a cids, a polylysine unit and the N-terminal labelled with the H-3-acety l group. The higher lipophilicity resulted in a higher Caco-2 cell ass ociation and also a higher rate of oral uptake. The addition of the po lylysine system increased the water solubility, as well as the oral up take of the conjugates. The conjugates developed have been absorbed an d detected after oral administration and appear to be stable for a con siderable time in vivo.