ABSTRACT
The penetration of intact particles in the nanometer range (nanoparticles, [NP]) through human skin is a controversial topic, which has attracted much interest from both the pharmaceutical and the personal care industries. Concerns have also been raised about the possible implications that dermal exposure to NP may have for human health, particularly from physical sunblock formulations. Here we use a theoretical approach to determine the feasibility of NP penetration of healthy human skin. The maximum flux of NPs of various dimensions is calculated based on two algorithms that have been developed to model passive diffusion of molecules through skin. The results confirm that NPs are too large to permeate skin by this mechanism. Although components of NPs may dissolve in the skin and measurable amounts have been detected in body fluids, this is not indicative of actual NP transport through the skin. The possible roles for NP formulations in drug permeation enhancement are also considered but are not associated with the penetration of intact NP.
REFERENCES
Gulson B, McCall M, Korsch M, Gomez L, Casey P, Oytam Y, et al. Small amounts of zinc from zinc oxide particles in sunscreens applied outdoors are absorbed through human skin. Toxicol Sci. 2010;118:140–9.
Gulson B, Wong H, Korsch M, Gomez L, Casey P, McCall M, et al. Comparison of dermal absorption of zinc from different sunscreen formulations and differing UV exposure based on stable isotope tracing. Sci Total Environ. 2012;420:313–8.
Miller G, Sales L. Nano-ingredients in sunscreen. The need for regulation. Friends of the Earth, Australia. 2012.
Lane ME. Nanoparticles and the skin—applications and limitations. J Microencapsulation. 2011;28:709–16.
Menon GK, Cleary GM, Lane ME. The structure and function of the stratum corneum. Int J Pharm. 2012;435:3–9.
Michaels AS, Chandrasekaran SK, Shaw JE. Drug permeation through human skin: theory and in vitro experimental measurement. AIChE. 1975;21:985–96.
Simonetti O, Hoogstraate AJ, Bialik W, Kempenaar JA, Schrijvers AH, Boddé HE, et al. Visualization of diffusion pathways across the stratum corneum of native and in-vitro-reconstructed epidermis by confocal laser scanning microscopy. Arch Dermatol Res. 1995;287:465–73.
Peck KD, Ghanem AH, Higuchi WI. Hindered diffusion of polar molecules through and effective pore radii estimates of intact and ethanol treated human epidermal membrane. Pharm Res. 1994;11:1306–14.
Peck KD, Ghanem AH, Higuchi WI. The effect of temperature upon the permeation of polar and ionic solutes through human epidermal membrane. J Pharm Sci. 1995;84:975–82.
Wang TF, Kasting GB, Nitsche JM. A multiphase microscopic diffusion model for stratum corneum permeability. I. Formulation, solution, and illustrative results for representative compounds. J Pharm Sci. 2006;95:620–48.
Wang TF, Kasting GB, Nitsche JM. A multiphase microscopic diffusion model for stratum corneum permeability. II. Estimation of physicochemical parameters, and application to a large permeability database. J Pharm Sci. 2007;96:3024–51.
Mitragotri S. Temperature dependence of skin permeability to hydrophilic and hydrophobic solutes. J Pharm Sci. 2007;96:1832–9.
Scheuplein RJ. Mechanism of percutaneous adsorption. I. Routes of penetration and the influence of solubility. J Invest Dermatol. 1965;45:334–46.
Scheuplein RJ. Mechanism of percutaneous absorption. II. Transient diffusion and the relative importance of various routes of skin penetration. J Invest Dermatol. 1967;48:79–88.
Kasting GB, Smith RL, Cooper ER. Effect of lipid solubility and molecular size on percutaneous absorption. In: Shroot B, Schaefer H, editors. Pharmacology and the skin: skin pharmacokinetics, volume 1. Basel: Karger; 1987. p. 138–53.
Onyenemezu CN, Gold D, Roman M, Miller WG. Diffusion of polystyrene latex spheres in linear polystyrene nonaqueous solutions. Macromolecules. 1993;26:3833–7.
Potts RO, Guy RH. Predicting skin permeability. Pharm Res. 1992;9:663–9.
Potts RO, Guy RH. A predictive algorithm for skin permeability: the effects of molecular size and hydrogen bond activity. Pharm Res. 1995;12:1628–33.
Yano T, Nakagawa A, Tsuji M, Noda K. Skin permeability of various non-steroidal anti-inflammatory drugs in man. Life Sci. 1986;39(12):1043–50.
Magnusson BM, Anissimov YG, Cross SE, Roberts MS. Molecular size as the main determinant of solute maximum flux across the skin. J Invest Dermatol. 2004;122:993–9.
Lademann J, Richter H, Schaefer UF, Blume-Peytavi U, Teichmann A, Otberg N, et al. Hair follicles—a long-term reservoir for drug delivery. Skin Pharmacol Physiol. 2006;19:232–6.
Lademann J, Richter H, Teichmann A, Otberg N, Blume-Peytavi U, Luengo J, et al. Nanoparticles—an efficient carrier for drug delivery into the hair follicles. Eur J Pharm Biopharm. 2007;66:159–64.
Ley EE, Bunge AL. Chemical transport in silicone rubber membranes from pure powders and saturated aqueous solutions. J Membr Sci. 2007;292:35–44.
Romonchuk WJ, Bunge AL. Permeation of 4-cyanophenol and methyl paraben from powder and saturated aqueous solution through silicone rubber membranes and human skin. J Pharm Sci. 2006;95:2526–33.
Mezei M, Gulasekharam V. Liposomes—a selective drug delivery system for the topical route of administration. Lotion dosage form. Life Sci. 1980;26:1473–7.
Cevc G, Schätzlein A, Blume G. Transdermal drug carriers, basic properties, optimization and transfer-efficiency in the case of epicutaneously applied peptides. J Control Release. 1995;36:3–16.
Dingler A, Blum RP, Niehus H, Müller RH, Gohla S. Solid lipid nanoparticles (SLN/Lipopearls)—a pharmaceutical and cosmetic carrier for the application of vitamin E in dermal products. J Microencapsul. 1999;16:751–67.
Maia CS, Mehnert W, Schäfer-Korting M. Solid lipid nanoparticles as drug carriers for topical glucocorticoids. Int J Pharm. 2000;196:165–7.
Pardeike J, Hommoss A, Müller RH. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm. 2009;366:170–84.
Ness SA. Factors affecting chemical permeation. In: Ness SA, editor. Surface and dermal monitoring for toxic exposures. New York: Wiley; pp. 31–45. 1994.
Santos P, Watkinson AC, Hadgraft J, Lane ME. Oxybutynin permeation in skin: the influence of drug and solvent activity. Int J Pharm. 2010;384:67–72.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Watkinson, A.C., Bunge, A.L., Hadgraft, J. et al. Nanoparticles Do Not Penetrate Human Skin—A Theoretical Perspective. Pharm Res 30, 1943–1946 (2013). https://doi.org/10.1007/s11095-013-1073-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11095-013-1073-9