New CeO 2 nanoparticles-based topical formulations for the skin protection against organophosphates -

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New CeO 2 nanoparticles-based topical formulations for the skin protection against organophosphates

Abstract

The study focuses on developing topical skin protectants (TSP) to reinforce skin protection against organophosphates (OPs), with a specific interest in cerium dioxide (CeO2) nanoparticles. The research examines the effect of adding CeO2 nanoparticles to TSP formulations, the impact of doping CeO2 nanoparticles with calcium, and the effect of two dispersion methods for CeO2 nanoparticles. The study used silicone membranes and Franz diffusion cells for permeation tests. The findings indicate that the addition of pure CeO2 nanoparticles in formulations significantly reduces penetration by a 3-4-fold factor. The study highlights that the O/W emulsion approach is optimal for creating a film-forming coating with good reproducibility of penetration results, while grafting nanoparticles to a thickener results in an efficient homogenous suspension of CeO2 nanoparticles with decreased toxicological impact, albeit with a less film-forming coating and slightly impacted reproducibility of penetration results.

Introduction

The paper discusses human exposure to organophosphates (OPs) in various contexts, including domestic, occupational, and incidental. OPs are used as pesticides and chemical warfare agents, inhibiting acetylcholinesterases and leading to paralysis and potential death. Main exposure routes are respiratory and dermal, and protective equipment and skin protectants are used to limit contact and absorption. The paper focuses on the potential use of nanoparticles (NPs) such as cerium oxide (CeO2) for skin protection against OPs and the impact of doping CeO2 NPs with calcium. Additionally, the paper explores the effectiveness of two dispersion methods for CeO2 NPs in topical formulations. In vitro permeation tests using silicone membranes are used to assess the efficacy of topical skin protectants against the toxic model OPs agent, paraoxon. The paper aims to observe the impact of CeO2 NP doping and the effect of dispersion methods on CeO2 NP effectiveness for skin protection against OPs.

 

 

Experimental

The study investigated the synthesis and functionalization of cerium oxide (CeO2) nanoparticles (NPs) and their efficacy in enhancing the barrier properties of silicone membranes against a toxic chemical, paraoxon (POX). CeO2 NPs were synthesized using a microwave-hydrothermal method and doped with calcium (Ca2+). X-ray diffraction analysis confirmed the presence of the CeO2 phase with a fluorite type cubic structure. The NPs were functionalized with amino groups and grafted onto a fluorocarbon copolymer. In vitro studies using Franz-type glass diffusion cells showed that membranes pre-treated with CeO2 NPs delayed and slowed down the permeation of POX, indicating their potential as toxicant security protectants (TSPs). Statistical analysis confirmed the significance of the findings. The research presents CeO2 NPs as promising candidates for enhancing the barrier efficacy of silicone membranes against toxic chemicals.

Results

The study compared the efficacy of cerium oxide nanoparticles (CeO2 NPs) when introduced in emulsion or grafted, and dispersed in formula versus polymeric matrix. The results showed that emulsions containing pure CeO2 NPs or Ca2+-doped CeO2 NPs significantly decreased penetration of UV filters, with maximal fluxes of 42% and 33% of the control, and reduced amounts of UV filters recovered in the receptor fluid. The efficacy of formulated CeO2 and Ca2+-doped CeO2 NPs was confirmed by their E values being greater than 1. The study also found that both polymers significantly reduced maximal flux and penetrated percent of UV filters recovered in the receptor fluid. Furthermore, the comparison between CeO2 NPs dispersed in emulsion and grafted to the polymer showed that grafting positively impacted the efficiency of CeO2 NPs. These findings suggest that the method of introducing and dispersing CeO2 NPs can greatly influence their efficacy.

Discussion:

The study evaluates the protection efficacy of cerium nanoparticles (NPs) against organophosphate (OP) penetration. In vitro permeation tests through silicone membranes are used for screening. The dispersion and protectant efficacy of cerium NPs are studied, with emphasis on their potential in comparison to pure and doped NPs. Emulsions containing NPs show improved protection compared to base emulsions, demonstrating the role of NPs in protection. Additionally, the study compares NPs dispersion in emulsions and grafting to a new fluorocarbon HASE polymer, finding that both methods offer protection but have different effectiveness and reproducibility. The NPs-emulsion and polymer systems show better protection than a commercially available barrier cream. The study also investigates the impact of calcium doping on the NPs’ efficiency and suggests covalent grafting of NPs onto polymer as a potential approach to limit their toxicological impact on the environment. Overall, the NPs show promising potential for use in protective formulations against OP penetration.

Conclusion

The study compared the effectiveness of cerium dioxide nanoparticles (CeO2 NPs) and calcium-doped CeO2 NPs for skin protection against the penetration of the OP toxic agent POX. The integration of CeO2 NPs in two formulations, O/W emulsions and grafting on a fluorocarbon associative polymer (HASE-F), was also investigated. The results showed that both formulations with NPs were more effective in enhancing protection properties compared to their base components. However, using free NPs as an active ingredient presented challenges such as aggregation in emulsions and potential health risks due to NP penetration and accumulation in biological membranes. On the other hand, grafting NPs on a fluorinated polymeric matrix showed homogeneous dispersion without toxicological issues but impacted reproducibility. The study concluded that the emulsion formulation was the best for obtaining a film-forming coating with good reproducibility of penetration results, and the introduction of the grafted polymer in a film-forming formula could be the best way to disperse NPs.

Reference:

ZENERINO, A., BOUTARD, T., BIGNON, C., AMIGONI, S., JOSSE, D., DEVERS, T. AND GUITTARD, F., 2015. New CeO2 nanoparticles-based topical formulations for the skin protection against organophosphates. Toxicology reports, 2, pp.1007-1013.