Characterization Methods for Nanoparticle-Skin Interactions: An Overview

Abstract

Research progresses have led to the development of different kinds of nanoplatforms to deliver drugs through different biological membranes. Particularly, nanocarriers represent a precious means to treat skin pathologies, due to their capability to solubilize lipophilic and hydrophilic drugs, to control their release, and to promote their permeation through the stratum corneum barrier. A crucial point in the development of nano-delivery systems relies on their characterization, as well as in the assessment of their interaction with tissues, in order to predict their fate under in vivo administration. The size of nanoparticles, their shape, and the type of matrix can influence their biodistribution inside the skin strata and their cellular uptake. In this respect, an overview of some characterization methods employed to investigate nanoparticles intended for topical administration is presented here, namely dynamic light scattering, zeta potential, scanning and transmission electron microscopy, X-ray diffraction, atomic force microscopy, Fourier transform infrared and Raman spectroscopy. In addition, the main fluorescence methods employed to detect the in vitro nanoparticles interaction with skin cell lines, such as fluorescence-activated cell sorting or confocal imaging, are described, considering different examples of applications. Finally, recent studies on the techniques employed to determine the nanoparticle presence in the skin by ex vivo and in vivo models are reported.

Keywords: confocal microscopy; fluorescence microscopy; hyperspectral microscopy; nanoparticles; skin; transmission electron microscopy.

Figure 1

Caffeic acid-containing solid lipid nanoparticles (a,b) and caffeic acid-containing ethosomes (c,d) obtained by transmission (a,c) or cryogenic transmission (b,d) electron microscopy. The bar corresponds to 150 nm in panels (a–c) and 50 nm in panel (d) [5].

Figure 2

The different ways nanocarriers can penetrate through the skin. Original figure created with BioRender.com.

Figure 3

The different nanocarrier uptake mechanisms. Original figure created with BioRender.com.

Figure 4

TEM micrographs of ethosome in the skin. (a) An ethosome (arrow) occurs in the intracellular space of the stratum corneum. (b) An ethosome (arrows) has been internalized in a corneocyte. In the high-magnification micrograph, the dark rim and the weakly electron-dense core of the ethosome (arrow) are clearly visible. (c) An ethosome (arrow) in the cytoplasm of a keratinocyte belonging to the stratum granulosum. (d) Ethosomes (arrows) make contact with mitochondria (m) and smooth endoplasmic reticulum cisternae (thin arrow in the inset) [151].

Figure 5

Analysis of licochalcone A (LA) or LA skin keratin liposomes loaded (LAL) distribution in abdominal skin of SD rats. (a) The fluorescence images of the skin samples treated with C6 (LA substitute) and C6L for 10, 20, 30, 40, 50, and 60 min. The scale bar is 100 μm; (b) the quantitative fluorescence intensities of C6 and C6L into skin at different time (** p < 0.01 vs. C6, n = 3) [139].