황체호르몬 유리호르몬(LHRH)의 경점막 수송: 토끼 점막균질액 중에서 [D-Ala6] LHRH의 효소적 분해 특성 및 중쇄지방산염의 안정화 효과

Transmucosal Delivery of Luteinizing Hormone-Releasing Hormone(LHRH):Enzymatic Proteolysis of [D-Ala6] LHRH and Inhibitory Effect of Medium Chain Fatty Acid Salts in Rabbit Mucosa

To investigate the feasibility of mucosal delivery of [D-Ala6] LHRH, a potent analogue of LHRH, enzymatic proteolysis of [D-Ala6] LHRH and inhibitory effect of medium chain fatty acid salts(MFA) were studied using rabbit mucosal homogenate. [D-Ala6] LHRH incubated in homogenates of rectal(RE), nasal(NA) and vaginal(VA) mucosa were assayed by HPLC. The degradation of [D-Ala6] LHRH followed the first order kinetics. The degradation products were found as [D-Ala6] LHRH1-7(m-i), to a lesser extent, [D-Ala6] LHRH1-9(m-ii) and [D-Ala6] LHRH1-3(m-iii) by the method of amino acid analysis(PITC method). The formation of [D-Ala6] LHRH1-7 was not inhibited by the addition of disodium ethylenediaminetetraacetic acid but inhibited by sodium tauro-24,25-dihydrofusidate, suggesting that endopeptidase 24.11(EP 24.11) cleaves the LeuK7-Arg8 bond of [D-Ala6] LHRH and is the primary [D-Ala6] LHRH degrading enzyme. The patterns of [D-Ala6] LHRH degradation indicated that EP 24.11 exists in each mucosal homogenate with the order of RE>NA>VA. MFA significantly inhibited the proteolysis of [D-Ala6] LHRH. The addition of sodium caprate(l.0%) or sodium laurate(O.5%) to the each mucosal homogenate completely protected [D-Ala6] LHRH from the degradation.