Blockage of skin invasion by schistosome cercariae by serine protease inhibitors

Invasion of skin by schistosome cercariae is facilitated by a serine protea se secreted from the acetabular cells of cercariae in response to skin lipi d. Specific inhibitors of the protease, when applied to human skin in formu lations designed to retain the inhibitor on and in the upper stratum corneu m layers, block cercarial invasion of human skin. Both peptide-based, irrev ersible inhibitors and non-peptide, reversible inhibitors block cercarial i nvasion when applied in a propylene glycol:isopropyl alcohol (3:1) formulat ion in vitro. Arrest of cercarial invasion could be achieved even after imm ersion of treated skin in water for 2 hr. Peptide-based irreversible inhibi tors in the presence of three different Topicare Delivery Compounds(R) opti mized arrest of cercarial invasion. The three Topicare Delivery Compounds(R ) applied alone prevented 80-100% of cercarial invasion. With inclusion of the inhibitor, there was 97-100% inhibition in vitro. The optimal formulati on with inhibitor was then applied to the tails of BALB/c mice, and the mic e were exposed to 120 cercariae by tail immersion. With the carrier lotion alone, there was a 50% reduction in worm burden and a 70% reduction in egg burden. When inhibitor was included, an 80% reduction in worm burden and a 92% reduction in egg burden was observed.