Advantages of cross-linked versus linear hyaluronic acid for semisolid skin delivery systems

Cross-linking of the hyaluronic acid (hyaluronan, HA) molecule may be a possible chemical modification via which to improve the problem of the penetration of HA. The successful preparation and characterization of stable nanoparticulate systems based on HA were described and discussed previously. The purpose of the present study is to compare hydrogels based on linear or cross-linked HA as potential semisolid drug delivery forms from the aspects of deep HA penetration through the skin. The rheological properties, hydration, irritation effect, in vitro and in vivo skin penetration were studied. The hydration effect was kept and the rheological parameters were slightly changed after the cross-linking procedure. Diffusion and penetration studies demonstrated that the formation of smaller particles of HA by means of cross-linking resulted in better diffusion through a synthetic membrane and better penetration through the human epidermis and living animal skin as compared with linear HA, which did not penetrate.