생체막점착성 하이드로겔을 이용한 황체형성호르몬 유리호르몬의 질점막 수송

Transvaginal Delivery of Luteinizing Hormone-Releasing Hormone Using Bioadhesive Hydrogel

The mucosal route of administration(nasal, buccal, conjunctival and vaginal) has recently been considered as an alternative to parenteral delivery for many peptide drugs because enzymatic degradation of these agents may be partly avoided. The objective of these study was to establish the optimal mucosal administration dosage form of $LHRH/[D-Ala^6]LHRH$, based on presystemic metabolism. We reported previously the peptidase inhibition effect of medium chain fatty acid salts(sodium caprylate, soadium caprate and sodium laurate), EDTA and STDHF on the proteolysis of $LHRH/[D-Ala^6]LHRH$ in rabbit mucosal homgenates. We also reported that EDTA, STDHF and sodium laurate markedly increased the potency of $LHRH/[D-Ala^6]LHRH$ solution applied vaginally. In the present study, by administration of polycarbophil hydrogel containing LHRH the ovulation inducing activity was 3.3 times greater than solution. These results indicate not only peptidase inhibitor but also polycarbophil hydrogel significantly improved the absorption of this drug. The results of this study would provide the feasibility as a rational dosage form for improving bioavailability and self administration of this hydrogel by the vaginal application.