Penetration of Metallic Nanoparticles in Human Full-Thickness Skin (Part One)

Biancamaria Baroli, Maria Grazia Ennas, Felice Loffredo, Michela Isola, Raimondo Pinna and M. Arturo Lo´pez-Quintela

The potential and benefits of nanoparticles in nanobiotechnology have been enthusiastically discussed inrecent literature; however, little is known about the potential risks of contamination by accidental contactduring production or use. Although theories of transdermal drug delivery suggest that skin structure andcomposition do not allow the penetration of materials larger than 600 Da, some articles on particle penetrationinto the skin have been recently published. Consequently, we wanted to evaluate whether metallicnanoparticles smaller than 10nm could penetrate and eventually permeate the skin. Two different stabilizednanoparticle dispersions were applied to excised human skin samples using vertical diffusion cells.At established time points, solutions in receiving chambers were quantified for nanoparticle concentration,and skin was processed for light transmission and electron microscope examination. The results of this studyshowed that nanoparticles were able to penetrate the hair follicle and stratum corneum (SC), occasionallyreaching the viable epidermis. Yet, nanoparticles were unable to permeate the skin. These results represent abreakthrough in skin penetration because it is early evidence where rigid nanoparticles have been shown topassively reach the viable epidermis through the SC lipidic matrix.

INTRODUCTION

Nanotechnology involves the design, production, characterization, and applications of materials (molecules or devices) whose dimensions are less than 100 nm. It has been shown that at nanometric scale, materials acquire new properties that can be exploited in numerous fields, including biotechnology, bioengineering, nanotechnology, and nanomedicine (Website of the Royal Society and Royal Academy of Engineering on Nanotechnology and Nanoscience, Final Report at www.nanotech.org.uk/index.htm, August 2006). Such materials are generally called nanomaterials. They can be categorized as nanotubes, nanowires, nanoshells, nanoparticles,quantum dots, dendrimers, and biopolymers (Website of the Royal Society and Royal Academy of Engineeringon Nanotechnology and Nanoscience, Final Report at www.nanotech.org.uk/index.htm, August 2006). Among these, nanoparticles could play an important role in nanomedicine. With regard to nanoparticles, rapid advances in nanotechnology have made it possible to synthesize different types of metallic and/or magnetic particles whose diameter is of the order of a few nanometers and even less. In addition, their surfaces can be modified by bioactive molecules or imaging probes that can be adsorbed, coated, conjugated, or linked to them. Owing to the wide applicability of such modified systems, they have been proposed for (i) cell labeling and targeting, (ii) tissue engineering, (iii) drug delivery, drug targeting, and magnetic drug targeting, (iv) magnetic resonance imaging, (v) hyperthermia, (vi) magnetofection, and (vii) analysis of biomolecules, to cite just a few (Penn et al., 2003; Gupta and Gupta, 2005; Neuberger et al., 2005). Many of these applications can also be tailored to target skin. For instance, cell labeling/targeting may help in the early diagnosis of a skin disease, which could also be treated with the goal of nanocarriers for drug delivery or targeting, hyperthermia, or magnetofection. In addition, a tissue engineering approach could be useful for skin wound healing therapies. Furthermore, the possibility of exploiting the magnetic properties of these particles might help in directing and localizing these agents in a particular layer of the skin where their action is desired.