Penetration of Microplastics and Nanoparticles Through Skin: Effects of Size, Shape, and Surface Chemistry

Abstract

Skin represents an effective barrier against the penetration of external agents into the human body. Nevertheless, recent research has shown that small particles, especially in the nanosized range, can not only penetrate through the skin but also work as vectors to transport active molecules such as contrast agents or drugs. This knowledge has opened new perspectives on nanomedicine and controlled drug delivery. On the other hand, micro- and nanoplastics represent a form of emerging pollutants, and their concentration in the environment has been reported to drastically increase in the last years. The possible penetration of these particles through the skin has become a major concern for human health. If the actual primary toxicity of these materials is still debated, their possible role in the transport of toxic molecules through the skin, originating as secondary toxicity, is surely alarming. In this review paper, we analyze and critically discuss the most recent scientific publications to underline how these two processes, (i) the controlled delivery of bioactive molecules by micro- and nano-structures and (ii) the unwanted and uncontrolled penetration of toxic species through the skin mediated by micro- and nanoparticles, are deeply related and their efficiency is strongly affected by the nature, size, and shape of the particles.

Keywords: drug delivery; microplastics; nanoparticles; nanoplastics; toxicity.

Figure 1

(a) The skin is composed of two main layers: the epidermis, made of closely packed epithelial cells, and the dermis, made of dense, irregular connective tissue that houses blood vessels, hair follicles, sweat glands, and other structures. Beneath the dermis lies the hypodermis, which is composed mainly of loose connective and fatty tissues. (b) The epidermis of thick skin has five layers: Stratum Basale, Stratum Spinosum, Stratum Granulosum, Stratum Lucidum, and Stratum Corneum. (Reported with permission from ref. [2]. Copyright Lumen Learning).

Figure 2

Schematic representation of (a) micro- and nanoplastics and their roles as emerging pollutants and in nanoparticle biomedicine and their application as (b) drug delivery systems or (c) antimicrobial agents.

Figure 3

Microplastics: toxicity in the human body. (Adapted with permission from ref. [34]. Copyright 2023, Elsevier).

Figure 4

SA/BG-SA_CM-PLGA_PFD delivery system action during the wound healing stages. (Reported with permission from ref. [50]. Copyright 2020, American Chemical Society).

Figure 5

(a) Scheme and photos of tensile adhesion test on the PAM/PDA/XL-MSN hydrogel to the porcine skin. (b) Scheme of the internalization process of R6G (red dots) from PAM/PDA/XL-MSN through the porcine skin tissue and its fluorescence microscope imaging in the time range of 0–24 h. (Adapted with permission from ref. [53]. Copyright 2020, John Wiley and Sons).

Figure 6

Accumulation of 500 nm nanoparticles in keratinocytes (a) and fibroblasts (b); accumulation of 100 nm nanoparticles in keratinocytes (c) and fibroblasts (d). (Adapted with permission from ref. [64]. Copyright 2024, Springer Nature).

Figure 7

Confocal laser microscope images of cross-sections of the rat skin of coumarin-6-loaded PLGA, PLGA-PEG-PLGA1004 (Mw: 4000/1000/4000, monomer composition of dl-lactic acid/glycolic acid/ethylene oxide = 62/22/16), and PLGA-PEG-PLGA1009 (Mw: 3500/4000/3500, monomer composition of dl-lactic acid/glycolic acid/ethylene oxide = 48/13/39) nanoparticles at 12 and 24 h from the initiation of the ex vivo skin permeability tests. (Reported with permission from ref. [91]. Copyright 2020, Elsevier).

Figure 8

(a) Microscope images and morphological observation of fibroblast cell lines with and without PS nanoparticles (size = 1000 nm at 1 μg/mL, 72 h after application). (b) A graphical representation of the number of PS nanoparticles taken up by cells. (Reported with permission from ref. [104]. Copyright 2024, Elsevier).

Figure 9

(a) Morphological characterization of the polystyrene fragments using field emission-scanning electron microscopy. (b) Size distribution of polystyrene fragments. (c) Schematic representation of the internalization path of polystyrene fragments in mammalian skin. (Adapted with permission from ref. [106]. Copyright 2024, Elsevier).