Nanocapsules appear a promising approach as a drug system for topical application. However, the transport mechanism of nanocapsule-associated drug through the skin is still being questioned. In the present study, the transport of chlorhexidine-loaded poly(Ε-caprolactone) nanocapsules through full-thickness and stripped hairless rat skin was investigated in static-diffusion cell. The chlorhexidine permeation profiles fitting the Fickian diffusion model showed that the drug encapsulation reduced the percutaneous drug absorption through stripped skin. Possible nanocapsule transport within skin conducts was suggested from the analysis of permeation parameters and confirmed by confocal laser microscopy studies. Furthermore, the chlorhexidine permeation and drug release data were highly correlated, suggesting that the magnitude of percutaneous absorption was controlled by the diffusion across the polymeric carrier. The behavior of nanocapsules at the skin interface was investigated by contact angle and surface tension measurements. The small ‘wetting’ of the nanocapsule on the stratum corneum surface preserved the mechanical integrity of the carrier characterized by a high specific surface at the skin interface. The flexibility of the nanocapsules assured a satisfying bioadhesion to the skin, whereas the rigidity of the carrier limited the molecular ‘spill’ into the skin and controlled the drug delivery to the skin.

Keywords:
Chlorhexidine, Nanocapsules, Hairless rat skin, Stratum corneum, Fickian diffusion, Surface tension, Rhodamine, Confocal laser microscopy
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© 2004 S. Karger AG, Basel
2004
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