Preparation of oligodimethylsiloxanes with sugar moiety at a terminal group as a transdermal penetration enhancer

Full Paper: Oligodimethylsiloxanes (ODMSs) containing glucose or cellobiose moiety at a terminal group were prepared to develop a silicone-based trans dermal penetration enhancer, Glucopiranosyl-terminated ODMS was pre pared b y the hydrosilylation of hydrosilyl-terminated ODMS with 1-allyl-beta -D-gl ucose tetraacetate followed by hydrolysis of the acetyl groups with sodium methoxide, to afford glucopiranosyl-terminated ODMS with a ether linkage be tween glucopiranosyl and ODMS components (GlcO-ODMS), and by the coupling r eaction of iodopropyl-terminated ODMS with 2-(2,3,4,6-O-tetraacetyl-beta -D -glucopyranosyl)thiopseudourea hydrobromide followed by the similar hydroly sis to afford glucopiranosyl-terminated ODMS with a thioether linkage (GlcS -ODMS). Cellobiosyl-terminated ODMS (Cell-ODMS) was also prepared by the si milar procedure as GlcO-ODMS. The enhancing activity of GlcO-ODMS, GluS-ODM S and Cell-ODMS on the drug permeation through the rabbit abdominal skin wa s evaluated by in vitro experiments using a two-chamber diffusion cell and antipyrine as a model drug. The permeation of antipyrine through the skin w as increased by the addition of GlcS-ODMS and GlcO-ODMS but not by Cell-ODM S. [GRAPHICS] Permeation profiles of antipyrine (ANP) through the rabbit abdominal skin w ith and without GlcO-ODMS and GlcS-ODMS as penetration enhancers. Each poin t represents mean +/- S.E. for 4 experiments. lozenge: GlcO-ODMS, o: GlcS-O DMS, .: control (without enhancer).