A novel method for the delivery of nitric oxide therapy to the skin of human subjects using a semi-permeable membrane.
Nitric oxide (NO) is a mediator of essential biological processes, including vasodilatation, anti-microbial activity and wound healing. A chemical system using sodium nitrite and ascorbic acid has been developed which generates significant amounts of NO. The originally described system was messy and impractical, and the high acidity may cause pain and further tissue damage in ulcerated skin. To overcome this, a selectively permeable, hydrophilic polyester co-polymer membrane system (Sympatex ) has been identified that can be placed between the NO-generating chemicals and the skin. The aim of the present study was to determine whether NO derived from this chemical system was able to diffuse through the membrane and have a measurable vasodilatory effect on forearm skin in healthy volunteers. The Sympatex 10 microm membrane was found to be highly permeable to NO, while preventing passage of the constituents of the NO-generation gel to the skin. The transmembrane NO-generation system had a vasodilatory effect comparable with that resulting from direct topical application. Additionally, the NO generated was effective in killing Staphylococcus aureus and Escherichia coli at doses lower than those required to increase skin blood flow. The vasodilatory and anti-microbial effects of this system may be useful as a patch-based topical therapy for skin ulceration, particularly when there is concomitant ischaemia and infection.
Department of Clinical Pharmacology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Charterhouse Square, London EC1M6BQ, UK.
J B
JB
Hardwick
A T
AT
Tucker
M
M
Wilks
A
A
Johnston
N
N
Benjamin
D000279:Administration, Cutaneous; D000328:Adult; D016503:Drug Delivery Systems / Q000379:methods*; D004926:Escherichia coli / Q000187:drug effects; D005542:Forearm / Q000098:blood supply; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D008567:Membranes, Artificial; D008833:Microcirculation / Q000187:drug effects; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000494:pharmacology; D010539:Permeability; D012867:Skin / Q000098:blood supply; D013211:Staphylococcus aureus / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D008567:Membranes, Artificial; D009569:Nitric Oxide