Enhancement of in vivo human skin penetration of resveratrol by chitosan-coated lipid microparticles

Abstract

In this study, lipid microparticles (LMs) uncoated or coated with chitosan, and containing the antioxidant polyphenol, resveratrol were developed in order to enhance its in vivo skin permeation. The LMs loaded with resveratrol were prepared by melt emulsification and sonication, using tristearin as lipidic material and hydrogenated phosphatidylcholine as the surfactant. Two different methods were examined for the coating of the LMs: chitosan addition during LM preparation or treatment of already formed LMs with a chitosan solution. The latter method achieved a better modulation of the in vitro release of resveratrol and hence was used for subsequent studies. The resveratrol loading and mean diameter of the LMs were 4.1 ± 0.3% (w/w) and 5.7 μm and 3.8 ± 0.2 % (w/w) and 6.1 μm for the uncoated and the chitosan-coated LMs, respectively. Chitosan coating changed the LM surface charge, from a negative zeta potential value (-17.8 ± 4.8 mV) for the uncoated particles, to a higher positive values (+64.2 ± 4.4 mV) for the chitosan-coated ones. Creams containing resveratrol free, encapsulated in the uncoated or chitosan-coated LMs were applied to the forearm of human volunteers and the penetration of the polyphenol in the stratum corneum was investigated in vivo by the tape stripping technique. Uncoated LMs did not produce any significant increase in the fraction of the applied resveratrol dose diffused in the stratum corneum (32.8 ± 8.9 %) compared to the control cream containing the non-encapsulated polyphenol (26.2 ± 5.6 % of the applied dose). On the other hand, application of the cream containing the chitosan-coated LMs produced a significant enhancement in the in vivo permeation of resveratrol to 49.3 ± 5.9% of the applied dose, the effect being more marked in the upper region of the horny layer. The observed improvement in the human stratum corneum penetration of resveratrol achieved by the LMs coated with chitosan should favour the efficiency of its topical application.

Keywords: Chitosan-coating; In vivo stratum corneum penetration profile; Lipid microparticles; Resveratrol; Skin penetration; Tape stripping.