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Sustained Ex Vivo Skin Antiseptic Activity Of Chlorhexidine In Poly(epsilon-caprolactone) Nanocapsule Encapsulated Form And As A Digluconate.

H. Lboutounne, Jean-François Chaulet, C. Ploton, F. Falson, F. Pirot
Published 2002 · Medicine, Chemistry

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In this work, the sustained bactericidal activity of chlorhexidine base loaded poly(epsilon-caprolactone), PCL, nanocapsules against Staphylococcus epidermidis inoculated onto porcine ear skin was investigated. Drug loaded nanocapsules were prepared by the interfacial polymer deposition following solvent displacement method, then characterized by photon correlation spectroscopy, electrophoretic measurements, transmission and scanning electron microscopy. Antimicrobial activity of these colloidal carriers was evaluated (i) in vitro against eight strains of bacteria, and (ii) ex vivo against Staphylococcus epidermidis inoculated for 12 h onto porcine ear skin surface treated for 3 min either with 0.6% chlorhexidine base loaded or unloaded nanocapsules suspended in hydrogel, or 1% chlorhexidine digluconate aqueous solution. Chlorhexidine absorption into the stratum corneum (SC) was evaluated by the tape-stripping method. The results showed that chlorhexidine nanocapsules in aqueous suspension having a 200-300 nm size and a positive charge exhibited similar minimum inhibitory concentrations against several bacteria with chlorhexidine digluconate aqueous solution. Ex vivo, there was a significant reduction in the number of colony forming units (CFUs) from 3-min treated skin with chlorhexidine nanocapsule suspension (5 to <1 log(10)) compared to chlorhexidine digluconate solution (5 to 2.02 log(10)) after a 8-h artificial contamination. After a 12-h artificial contamination, both formulations failed to achieve a 5 log(10) reduction. Furthermore, from a 3-min treatment with an identical applied dose and a subsequent 12-h artificial contamination, a residual chlorhexidine concentration in the SC was found to be three-fold higher with chlorhexidine nanocapsule suspension than with chlorhexidine digluconate solution. Interestingly, nanocapsules were shown in porcine skin follicles. Consequently, a topical application of chlorhexidine base-loaded positively charged nanocapsules in an aqueous gel achieved a sustained release of bactericide against Staphylococcus epidermidis for at least 8 h. Enhancement of drug delivery by mediating a more direct and prolonged contact between the carrier and (i) bacteria, (ii) skin surface, and (iii) skin follicles was assumed.
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