Penetration and Translocation of Nanoparticles through Skin

University Of Rochester, Rochester NY

Investigators

Abstract

CBET-0837891 DeLouise Objectives: Advances in the synthesis and control of engineered nanoparticles (NP) properties has escalated their use in numerous diverse applications ranging from medicine to energy. Currently NPs are formulated in over 400 consumer products (eg. sunblocks, food containers). A consequence of this nanotechnology boom is an increased risk of unintended NP exposure with human skin, the largest organ in the body. The proposed research is motivated by the increasing use of metal oxide (ZnO and TiO2) NPs in daily-use cosmetic products to protect against ultraviolet radiation (UVR) exposure. Our main objective of this research is to quantify NP skin penetration and to generate molecular level insight into the mechanisms of translocation by contrasting permeation through normal and barrier compromised skin induced by UVR. Experimental Approach: We will utilize in vivo, ex vivo and in vitro models to quantify the effects of UVR on NP permeation and translocation. Mechanistic insight will be gleaned by investigating penetration as a function of NP surface chemistry and vehicle including incorporation of chemical penetration enhancers (CPE) to modify the skin barrier by extraction or fluidization of skin lipids. The central hypothesis of the proposed research is that the NP surface chemistry (charge/hydrophobicity) and hydrodynamic size are the most important material properties that effect skin penetration. Tissue clearance and toxicity also depend on composition but these are not a focus of this proposal. Specific Aim 1: Develop an in vivo mouse model to investigate NP skin penetration and generate mechanistic insight on NP translocation as a function of NP size, surface chemistry, vehicle and skin status (normal vs. UV exposed). Specific Aim 2: Translate knowledge gained in Aim 1 to a human system using an ex vivo skin model to quantify the affect of skin physiology and UVR on NP penetration. S pecific Aim 3: Develop an in vitro differentiated keratinocyte model to investigate NP up-take and cytotoxicty as a function of NP surface chemistry and UVR and to elucidate knowledge on localization aspects discovered in Aim 2. Expected Results: These studies will be among the first to generate in vivo data on a wide range of NP types (quantum dots, fluorescent polymer, metal oxides) as a function of skin barrier status. Our study will increase understanding of the mechanisms and driving forces of skin barrier function against NP penetration. Results from this research will generate knowledge on how to design NPs to limit bioavailability and prevent potential side effects from skin exposure. We will develop understanding that will enable future work to be done in more specific targeting of nanoparticles to prevent or enhance bio availability. This knowledge could be used to develop powerful drug delivery agents or to decrease penetration of cosmetic nanoparticles. Broader Impact: A primary outcome of this work will be to provide education and mentoring to graduate, undergraduate and high school students in a highly interdisciplinary research environment spanning aspects of material science, surface chemistry, skin biology, and biomedical engineering. The concepts of quantum dots and nanotoxicity will be integrated into lectures presented in Cell and Tissue Engineering (BME462) and Nanobiophotoics (ECE580) courses given by the PI. Graduate and undergraduate students involved in this research will be trained to pursue a variety of challenging career paths in the high-tech and biotech sectors of industry, government, and academia. Supplemental Keywords: nanotechnology, nanomaterials, nanoparticles, polymer, quantum dots, metals, metal oxides, semiconductor nanocrystals, human skin, skin permeation, UV radiation, bioavailability, cell culture, human health effects, dermal contact, human exposure.