Margaret E.K. Kraeling1, Vanessa D. Topping1, Kathleen R. Belgrave1, Kristian Schlick2, Eric Simanek2, Sonny Man3, Sureshbabu Dadiboyena4,5, Anil K. Patri4, Robert L. Sprando1, and Jeffrey J. Yourick1
- Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, Laurel, Maryland.
- Department of Chemistry, Texas Christian University, Fort Worth, Texas.
- Nanotechnology Characterization Laboratory, Leidos Biomedical Research, Inc, Frederick, Maryland.
- Nanotechnology Core Facility, Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas.
- FDA Commissioner’s Fellowship Program, Office of Chief Scientist, Office of the Commissioner, Silver Spring, Maryland.
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.
CovalX Technology Used
This research evaluates the effect of dendrimer on increasing the skin penetration in the presence of glycolic acid (GA) which is commonly used in many cosmetic products, and to determine the systemic bioavailability of the dendrimer. TOF Mass spectrometer equipped with a CovalX HM-1 high mass detector was used on all purified dendrimer samples. MALDI-TOF Matrix solution, 2,5-dihydroxybenzoic acid, was used in the pre-analysis phase. With the use of MALDI-TOF mass spectrometry, the researchers were able to determine the enhanced penetration of GA when mixed with G4-OH dendrimers compared with GA alone.