Introduction: Dendrimers are highly branched, stable polymeric nanoparticles with functional groups capable of binding other molecules and may increase delivery of chemicals into skin. Materials and Methods: We examined the skin penetration of generation 3 (G3) to generation 6 (G6) polyamidoamine (PAMAM) amine-terminated (positively charged) dendrimer nanoparticles conjugated with a fluorophore (Alexa Fluor 568) for confocal imaging. The PAMAM dendrimers were further conjugated with succinic anhydride (negative surface charge) or glycidol to impart no charge (neutral). Dendrimers were applied (0.2% concentration) in aqueous solutions or cosmetic formulation onto viable pig or human cadaver skin assembled in diffusion cells. Results: After a 24-hour exposure, most fluorescence appeared in the stratum corneum (SC) or in hair follicles of both pig and human skin. We then examined the skin penetration of radiolabeled generation 4 (G4) dendrimer (0.2% concentration), conjugated with glycidol (OH) and G4 dendrimer bound to glycolic acid (GA), to determine if enhanced skin penetration of GA could occur. The skin penetration of a radiolabeled GA solution and a GA G4-OH dendrimer solution mixture was also evaluated. Most of the radioactive G4-OH dendrimer penetrating human skin remained in the SC (4.7%), with less than 1% absorbing into the epidermis and dermis. When the radiolabeled G4 dendrimer was bound to GA, penetration into SC increased significantly to 29%, and to 4% in the epidermis and dermis compared with the radiolabeled GA treatment alone (4.6%) and the radiolabeled GA G4-OH dendrimer mixture (3.4%). Using radioactivity as a marker, when labeled G4 dendrimer was bound to GA and applied to skin, there was an increase in total skin levels and total penetration levels when compared with GA and GA-dendrimer mixture. Discussion and Conclusion: It appears that the G4 dendrimer may increase the penetration of GA, demonstrating that dendrimer terminal group functionality and charge may alter skin absorption of associated chemicals.
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