Blockage of skin invasion by schistosome cercariae by serine protease inhibitors.
Invasion of skin by schistosome cercariae is facilitated by a serine protease secreted from the acetabular cells of cercariae in response to skin lipid. Specific inhibitors of the protease, when applied to human skin in formulations designed to retain the inhibitor on and in the upper stratum corneum layers, block cercarial invasion of human skin. Both peptide-based, irreversible inhibitors and non-peptide, reversible inhibitors block cercarial invasion when applied in a propylene glycol:isopropyl alcohol (3:1) formulation in vitro. Arrest of cercarial invasion could be achieved even after immersion of treated skin in water for 2 hr. Peptide-based irreversible inhibitors in the presence of three different Topicare Delivery Compounds optimized arrest of cercarial invasion. The three Topicare Delivery Compounds applied alone prevented 80-100% of cercarial invasion. With inclusion of the inhibitor, there was 97-100% inhibition in vitro. The optimal formulation with inhibitor was then applied to the tails of BALB/c mice, and the mice 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.
Lim
K C
KC
Department of Pathology, University of California, San Francisco 94121, USA.
Sun
E
E
Bahgat
M
M
Bucks
D
D
Guy
R
R
Hinz
R S
RS
Cullander
C
C
McKerrow
J H
JH
D019840:2-Propanol; D000287:Administration, Topical; D000590:Amino Acid Chloromethyl Ketones / Q000627:therapeutic use*; D000818:Animals; D004121:Dimethyl Sulfoxide; D004337:Drug Carriers; D006801:Humans; D008099:Liver / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D009284:Naphthols / Q000494:pharmacology / Q000627:therapeutic use*; D010270:Parasite Egg Count; D011092:Polyethylene Glycols; D012550:Schistosoma mansoni / Q000187:drug effects*; D012555:Schistosomiasis mansoni / Q000517:prevention & control*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects* / Q000469:parasitology
D000590:Amino Acid Chloromethyl Ketones; D004337:Drug Carriers; D009284:Naphthols; D015842:Serine Proteinase Inhibitors; D011092:Polyethylene Glycols; D019840:2-Propanol; D004121:Dimethyl Sulfoxide