Generic placeholder image

Current Nanotoxicity and Prevention (Discontinued)

Editor-in-Chief

ISSN (Print): 2665-9808
ISSN (Online): 2665-9816

Review Article

In vitro and In vivo Toxicity Assessment of Metallic Nanoparticulate Systems for Skin Targeting

Author(s): Sanju Nanda*, Sheefali Mahant, Pragya Sharma and Surbhi Dhawan

Volume 1, Issue 1, 2021

Published on: 10 January, 2021

Page: [92 - 110] Pages: 19

DOI: 10.2174/2665980801666210111110927

Open Access Journals Promotions 2
Abstract

In recent decades, nanoscience and nanotechnology have played a revolutionary role in the therapeutic domain. Manipulation of atoms and molecules at the nanometric scale endows biomaterials with specific physicochemical properties. Skin being the largest organ of the human body and an extensively exploited route for drug delivery, is one of the primary sites for exposure to nanoparticulate matter. Skin care products and cosmetics also constitute a major source of exposure to metallic nanoparticles. Metallic nanoparticles are widely used for therapeutic, diagnostic and cosmetic purposes. The potential risks associated with their use in modern medicine are a subject of extensive research. The present article aims to discuss the toxicity concerns associated with the use of metallic nanoparticles in dermatological products, and provide an overview of their in vitro and in vivo methods of nanotoxicity assessment, as per OECD guidelines. It also presents a concise account of the lacunae in the existing guideline, which need to be addressed in order to adapt the prescribed tests to the testing of nanoparticles. The review also gives an insight into the gaps in the in vitro, in vivo correlation of data furnished by various research groups. It provides a glimpse of important regulatory aspects applicable to the evaluation of topically applied nanoparticulate systems. In the end, it discusses the challenges and future perspectives in order to strengthen the scientific investigations in this domain.

Keywords: Nanocosmetics, OECD guidelines, skin targeting, nanotoxicity, risk assessment, regulatory status.

Graphical Abstract
[1]
D R, Rao P. Nanoparticles: Is toxicity a concern? EJIFCC 2011; 22(4): 92-101.
[PMID: 27683397]
[2]
Antonio JR, Antônio CR, Cardeal IL, Ballavenuto JM, Oliveira JR. Nanotechnology in dermatology. An Bras Dermatol 2014; 89(1): 126-36.
[http://dx.doi.org/10.1590/abd1806-4841.20142228] [PMID: 24626657]
[3]
Kumar V, Sharma N, Maitra SS. In vitro and in vivo toxicity assessment of nanoparticles. Int Nano Lett 2017; 7(4): 243-56.
[http://dx.doi.org/10.1007/s40089-017-0221-3]
[4]
Wang M, Lai X, Shao L, Li L. Evaluation of immunoresponses and cytotoxicity from skin exposure to metallic nanoparticles. Int J Nanomedicine 2018; 13: 4445-59.
[http://dx.doi.org/10.2147/IJN.S170745] [PMID: 30122919]
[5]
Crosera M, Bovenzi M, Maina G, et al. Nanoparticle dermal absorption and toxicity: a review of the literature. Int Arch Occup Environ Health 2009; 82(9): 1043-55.
[http://dx.doi.org/10.1007/s00420-009-0458-x] [PMID: 19705142]
[6]
Takhar P, Mahant S. In vitro methods for nanotoxicity assessment: advantages and applications. Arch Appl Sci Res 2011; 3(2): 389-403.
[7]
Sahu SC, Hayes AW. Toxicity of nanomaterials found in human environment: a literature review. Toxicol Res App 2017; 1: 1-13.
[http://dx.doi.org/10.1177/2397847317726352]
[8]
Jeswani G, Paul SD, Chablani L. Safety and toxicity counts of nanocosmetics. Nanocosmetics 2019; 299-335.
[http://dx.doi.org/10.1007/978-3-030-16573-4_14]
[9]
Hashempour S, Ghanbarzadeh S, Maibach HI, Ghorbani M, Hamishehkar H. Skin toxicity of topically applied nanoparticles. Ther Deliv 2019; 10(6): 383-96.
[http://dx.doi.org/10.4155/tde-2018-0060] [PMID: 31184548]
[10]
Baroli B. Penetration of nanoparticles and nanomaterials in the skin: fiction or reality? J Pharm Sci 2010; 99(1): 21-50.
[http://dx.doi.org/10.1002/jps.21817] [PMID: 19670463]
[11]
Gupta R, Xie H. Nanoparticles in daily life: applications, toxicity and regulations. J Environ Pathol Toxicol Oncol 2018; 37(3): 209-30.
[12]
Mahant S, Rao R, Nanda S. Nanostructured lipid carriers: Revolutionizing skin care and topical therapeutics. In: Grumezescu AM, Ed. Design of Nanostructures for Versatile Therapeutic Applications 2018; 97-136.
[13]
Mahant S, Kumar S, Pahwa R, Kaushik D, Nanda S, Rao R. Solid lipid nanoparticles in drug delivery for skincare. Keservani RK 2019; 32: 337.
[http://dx.doi.org/10.1201/9781351137263-10]
[14]
Jatana S, DeLouise LA. Understanding engineered nanomaterial skin interactions and the modulatory effects of ultraviolet radiation skin exposure. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2014; 6(1): 61-79.
[http://dx.doi.org/10.1002/wnan.1244] [PMID: 24123977]
[15]
Labouta HI, el-Khordagui LK, Kraus T, Schneider M. Mechanism and determinants of nanoparticle penetration through human skin. Nanoscale 2011; 3(12): 4989-99.
[http://dx.doi.org/10.1039/c1nr11109d] [PMID: 22064944]
[16]
Wiechers JW, Musee N. Engineered inorganic nanoparticles and cosmetics: facts, issues, knowledge gaps and challenges. J Biomed Nanotechnol 2010; 6(5): 408-31.
[http://dx.doi.org/10.1166/jbn.2010.1143] [PMID: 21329039]
[17]
Tak YK, Pal S, Naoghare PK, Rangasamy S, Song JM. Shape-dependent skin penetration of silver nanoparticles: does it really matter? Sci Rep 2015; 5: 16908.
[http://dx.doi.org/10.1038/srep16908] [PMID: 26584777]
[18]
Larese Filon F, Bello D, Cherrie JW, Sleeuwenhoek A, Spaan S, Brouwer DH. Occupational dermal exposure to nanoparticles and nano-enabled products: Part I-Factors affecting skin absorption. Int J Hyg Environ Health 2016; 219(6): 536-44.
[http://dx.doi.org/10.1016/j.ijheh.2016.05.009] [PMID: 27289581]
[19]
Brouwer DH, Spaan S, Roff M, et al. Occupational dermal exposure to nanoparticles and nano-enabled products: Part 2, exploration of exposure processes and methods of assessment. Int J Hyg Environ Health 2016; 219(6): 503-12.
[http://dx.doi.org/10.1016/j.ijheh.2016.05.003] [PMID: 27283207]
[21]
21. Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Guidelines 7th revised edition. 2017. https://www.unece.org/fileadmin/DAM/trans/danger/publi/ghs/ghs_rev07/English/ST_SG_AC10_30_Rev7e.pdf
[22]
Wu T, Tang M. Review of the effects of manufactured nanoparticles on mammalian target organs. J Appl Toxicol 2018; 38(1): 25-40.
[http://dx.doi.org/10.1002/jat.3499] [PMID: 28799656]
[23]
Murthy PB, Kishore AS, Surekha P. Assessment of in vitro skin irritation potential of nanoparticles: RHE model. Methods Mol Biol 2012; 926: 219-34.
[http://dx.doi.org/10.1007/978-1-62703-002-1_16] [PMID: 22975968]
[25]
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65(1-2): 55-63.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]
[28]
Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Guidelines 5th revised edition. 2013. https://www.unece.org/fileadmin/DAM/trans/danger/publi/ghs/ghs_rev05/English/ST-SG-AC10-30-Rev5e.pdf
[30]
Fentem JH, Archer GEB, Balls M, et al. The ECVAM International validation study on in vitro tests for skin corrosivity. 2. Results and Evaluation by the Management Team. Toxicol In Vitro 1998; 12(4): 483-524.
[http://dx.doi.org/10.1016/S0887-2333(98)00019-8] [PMID: 20654431]
[32]
Balls M, Hellsten E. Statement on the application of the CORROSITEX assay for skin corrosivity testing. Altern Lab Anim 2001; 29(2): 96-7.
[PMID: 11379538]
[33]
Bauer D, Averett LA, De Smedt A, et al. Standardized UV-vis spectra as the foundation for a threshold-based, integrated photosafety evaluation. Regul Toxicol Pharmacol 2014; 68(1): 70-5.
[http://dx.doi.org/10.1016/j.yrtph.2013.11.007] [PMID: 24269723]
[34]
Lovell WW. A scheme for in vitro screening of substances for photoallergenic potential. Toxicol In Vitro 1993; 7(1): 95-102.
[http://dx.doi.org/10.1016/0887-2333(93)90117-N] [PMID: 20732176]
[35]
Borenfreund E, Puerner JA. Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicol Lett 1985; 24(2-3): 119-24.
[http://dx.doi.org/10.1016/0378-4274(85)90046-3] [PMID: 3983963]
[37]
Gerberick GF, Vassallo JD, Foertsch LM, Price BB, Chaney JG, Lepoittevin JP. Quantification of chemical peptide reactivity for screening contact allergens: a classification tree model approach. Toxicol Sci 2007; 97(2): 417-27.
[http://dx.doi.org/10.1093/toxsci/kfm064] [PMID: 17400584]
[38]
Emter R, Ellis G, Natsch A. Performance of a novel keratinocyte-based reporter cell line to screen skin sensitizers in vitro. Toxicol Appl Pharmacol 2010; 245(3): 281-90.
[http://dx.doi.org/10.1016/j.taap.2010.03.009] [PMID: 20307559]
[39]
Andreas N, Caroline B, Leslie F, et al. The intra- and inter-laboratory reproducibility and predictivity of the KeratinoSens assay to predict skin sensitizers in vitro: results of a ring-study in five laboratories. Toxicol In Vitro 2011; 25(3): 733-44.
[http://dx.doi.org/10.1016/j.tiv.2010.12.014] [PMID: 21195160]
[42]
OECD Guideline for the Testing of Chemicals. OECD/OCDE 402, Guidelines governing Acute Dermal Toxicity. Fixed Dose Procedure 2017; 9
[http://dx.doi.org/10.1787/9789264070585-en]
[43]
Erhirhie EO, Ihekwereme CP, Ilodigwe EE. Advances in acute toxicity testing: strengths, weaknesses and regulatory acceptance. Interdiscip Toxicol 2018; 11(1): 5-12.
[http://dx.doi.org/10.2478/intox-2018-0001] [PMID: 30181707]
[44]
Hazard Communication Information Sheet reflecting the US OSHA Implementation of the Globally Harmonized System (GHS) of Classification and Labelling of Chemicals. Produced by the SCHC-OSHA Alliance on Acute Dermal Toxicity 2018.
[45]
OECD 411, Guidelines governing Subchronic Dermal Toxicity: 90-day Study. OECD Guideline for the Testing of Chemicals 1981.
[47]
Adler S, Basketter D, Creton S, et al. Alternative (non-animal) methods for cosmetics testing: current status and future prospects-2010. Arch Toxicol 2011; 85(5): 367-485.
[http://dx.doi.org/10.1007/s00204-011-0693-2] [PMID: 21533817]
[48]
OECD 471, Guidelines governing Bacterial Reverse Mutation Test. OECD Guideline for the Testing of Chemicals 1997.
[49]
OECD/OCDE 473, Guidelines governing in vitro Mammalian Chromosomal Aberration Test. OECD Guideline for the Testing of Chemicals 2016.
[50]
OECD/OCDE 476, Guidelines governing in vitro Mammalian Cell Gene Mutation Tests using the Hprt and xprt genes. OECD Guideline for the Testing of Chemicals 2016.
[51]
OECD/OCDE 474, Guidelines governing Mammalian Erythrocyte Micronucleus Test. OECD Guideline for the Testing of Chemicals 2016.
[52]
OECD/OCDE 489, Guidelines governing In Vivo Mammalian Alkaline Comet Assay. OECD Guideline for the Testing of Chemicals 2016.
[53]
OECD 410, Guidelines governing Repeated Dose Dermal Toxicity: 21/28-day Study. OECD Guideline for the Testing of Chemicals 1981.
[54]
OECD/OCDE 427, Guidelines governing Skin Absorption: in vivo Method. OECD Guideline for the Testing of Chemicals 2004.
[55]
OECD/OCDE 428, Guidelines governing Skin Absorption: in vitro Method. OECD Guideline for the Testing of Chemicals 2004.
[56]
Miyani VA, Hughes MF. Assessment of the in vitro dermal irritation potential of cerium, silver, and titanium nanoparticles in a human skin equivalent model. Cutan Ocul Toxicol 2017; 36(2): 145-51.
[http://dx.doi.org/10.1080/15569527.2016.1211671] [PMID: 27439971]
[57]
Kim H, Choi J, Lee H, et al. Skin corrosion and irritation test of nanoparticles using reconstructed three-dimensional human skin model, EpiDermTM. Toxicol Res 2016; 32(4): 311-6.
[http://dx.doi.org/10.5487/TR.2016.32.4.311] [PMID: 27818733]
[58]
Vinardell MP, Llanas H, Marics L, Mitjans M. In vitro comparative skin irritation induced by nano and non-nano zinc oxide. Nanomaterials (Basel) 2017; 7(3): 56.
[http://dx.doi.org/10.3390/nano7030056] [PMID: 28336890]
[59]
Wakure BS, Bhatia NM. Acute dermal toxicity and irritability studies of Ag2Ga nanoneedle mediated silver formulation as per OECD 402 and 404 protocols. Int J Pharm Sci Res 2018; 9(9): 4015-20.
[60]
Korani M, Rezayat SM, Arbabi Bidgoli S. Sub-chronic dermal toxicity of silver nanoparticles in guinea pig: Special emphasis to heart, bone and kidney toxicities. Iran J Pharm Res 2013; 12(3): 511-9.
[PMID: 24250657]
[61]
Korani M, Rezayat SM, Ghamami SG. Silver nanoparticle induced muscle abnormalities: A sub-chronic dermal assessment in guinea pig. J Pharm Health Sci 2012; 1(3): 21-9.
[62]
Korani M, Rezayat SM, Gilani K, Arbabi Bidgoli S, Adeli S. Acute and subchronic dermal toxicity of nanosilver in guinea pig. Int J Nanomedicine 2011; 6: 855-62.
[http://dx.doi.org/10.2147/IJN.S17065] [PMID: 21720498]
[63]
Meyer K, Rajanahalli P, Ahamed M, Rowe JJ, Hong Y. ZnO nanoparticles induce apoptosis in human dermal fibroblasts via p53 and p38 pathways. Toxicol In Vitro 2011; 25(8): 1721-6.
[http://dx.doi.org/10.1016/j.tiv.2011.08.011] [PMID: 21903158]
[64]
Mateo D, Morales P, Avalos A, Haza AI. Comparative cytotoxicity evaluation of different size gold nanoparticles in human dermal fibroblasts. J Exp Nanosci 2015; 10(18): 1401-17.
[http://dx.doi.org/10.1080/17458080.2015.1014934]
[65]
Benameur L, Auffan M, Cassien M, et al. DNA damage and oxidative stress induced by CeO2 nanoparticles in human dermal fibroblasts: Evidence of a clastogenic effect as a mechanism of genotoxicity. Nanotoxicology 2015; 9(6): 696-705.
[http://dx.doi.org/10.3109/17435390.2014.968889] [PMID: 25325158]
[66]
Park YH, Jeong SH, Yi SM, et al. Analysis for the potential of polystyrene and TiO2 nanoparticles to induce skin irritation, phototoxicity, and sensitization. Toxicol In Vitro 2011; 25(8): 1863-9.
[http://dx.doi.org/10.1016/j.tiv.2011.05.022] [PMID: 21664450]
[67]
Pernodet N, Fang X, Sun Y, et al. Adverse effects of citrate/gold nanoparticles on human dermal fibroblasts. Small 2006; 2(6): 766-73.
[http://dx.doi.org/10.1002/smll.200500492] [PMID: 17193121]
[68]
Pan Z, Lee W, Slutsky L, Clark RA, Pernodet N, Rafailovich MH. Adverse effects of titanium dioxide nanoparticles on human dermal fibroblasts and how to protect cells. Small 2009; 5(4): 511-20.
[http://dx.doi.org/10.1002/smll.200800798] [PMID: 19197964]
[69]
Park YH, Kim JN, Jeong SH, et al. Assessment of dermal toxicity of nanosilica using cultured keratinocytes, a human skin equivalent model and an in vivo model. Toxicology 2010; 267(1-3): 178-81.
[http://dx.doi.org/10.1016/j.tox.2009.10.011] [PMID: 19850098]
[70]
Ryu HJ, Seo MY, Jung SK, et al. Zinc oxide nanoparticles: a 90- day repeated-dose dermal toxicity study in rats. Int J Nanomedicine 2014; 9(2)(Suppl. 2): 137-44.
[PMID: 25565832]
[71]
Sharma V, Singh SK, Anderson D, Tobin DJ, Dhawan A. Zinc oxide nanoparticle induced genotoxicity in primary human epidermal keratinocytes. J Nanosci Nanotechnol 2011; 11(5): 3782-8.
[http://dx.doi.org/10.1166/jnn.2011.4250] [PMID: 21780369]
[72]
Ng KW, Khoo SP, Heng BC, et al. The role of the tumor suppressor p53 pathway in the cellular DNA damage response to zinc oxide nanoparticles. Biomaterials 2011; 32(32): 8218-25.
[http://dx.doi.org/10.1016/j.biomaterials.2011.07.036] [PMID: 21807406]
[73]
Wills JW, Hondow N, Thomas AD, et al. Genetic toxicity assessment of engineered nanoparticles using a 3D in vitro skin model (EpiDerm™). Part Fibre Toxicol 2016; 13(1): 50.
[http://dx.doi.org/10.1186/s12989-016-0161-5] [PMID: 27613375]
[74]
Law RM, Ngo MA, Maibach HI. Twenty clinically pertinent factors/observations for percutaneous absorption in humans. Am J Clin Dermatol 2020; 21(1): 85-95.
[http://dx.doi.org/10.1007/s40257-019-00480-4] [PMID: 31677110]
[75]
N’Da DD. Prodrug strategies for enhancing the percutaneous absorption of drugs. Molecules 2014; 19(12): 20780-807.
[http://dx.doi.org/10.3390/molecules191220780] [PMID: 25514222]
[76]
Georgountzou A, Papadopoulos NG. Postnatal innate immune development: from birth to adulthood. Front Immunol 2017; 11(8): 957.
[http://dx.doi.org/10.3389/fimmu.2017.00957]
[77]
Sunderkötter C, Kalden H, Luger TA. Aging and the skin immune system. Arch Dermatol 1997; 133(10): 1256-62.
[http://dx.doi.org/10.1001/archderm.1997.03890460078009] [PMID: 9382564]
[78]
Pyo SM, Maibach HI. Skin metabolism: relevance of skin enzymes for rational drug design. Skin Pharmacol Physiol 2019; 32(5): 283-94.
[http://dx.doi.org/10.1159/000501732] [PMID: 31357203]
[79]
Ruela AL, Perissinato AG, Lino ME, Mudrik PS, Pereira GR. Evaluation of skin absorption of drugs from topical and transdermal formulations. Braz J Pharm Sci 2016; 52(3): 527-44.
[80]
Gober MD, Gaspari AA. Allergic contact dermatitis. Curr Dir Autoimmun 2008; 10: 1-26.
[http://dx.doi.org/10.1159/000131410] [PMID: 18460878]
[81]
Groeber F, Holeiter M, Hampel M, Hinderer S, Schenke-Layland K. Skin tissue engineering--in vivo and in vitro applications. Adv Drug Deliv Rev 2011; 63(4-5): 352-66.
[http://dx.doi.org/10.1016/j.addr.2011.01.005] [PMID: 21241756]
[82]
Bojar RA. Studying the human skin microbiome using 3D in vitro skin models. Appl In Vitro Toxicol 2015; 1(2): 165-71.
[http://dx.doi.org/10.1089/aivt.2015.0002]
[83]
Mahant S, Rao R, Souto EB, Nanda S. Analytical tools and evaluation strategies for nanostructured lipid carrier-based topical delivery systems. Expert Opin Drug Deliv 2020; 17(7): 963-92.
[http://dx.doi.org/10.1080/17425247.2020.1772750] [PMID: 32441158]
[84]
Alépée N, Grandidier MH, Tornier C, Cotovio J. An integrated testing strategy for in vitro skin corrosion and irritation assessment using SkinEthic™ Reconstructed Human Epidermis. Toxicol In Vitro 2015; 29(7): 1779-92.
[http://dx.doi.org/10.1016/j.tiv.2015.07.012] [PMID: 26187475]
[85]
Chen L, Wu M, Jiang S, et al. Skin Toxicity Assessment of Silver Nanoparticles in a 3D Epidermal Model Compared to 2D Keratinocytes. Int J Nanomedicine 2019; 14: 9707-19.
[http://dx.doi.org/10.2147/IJN.S225451] [PMID: 31849463]
[86]
Tissue Model EpiDerm™. (Available from: https://www.mattek.com/products/epiderm/
[87]
SkinEthic RHE/Human Epidermis. (Available from: https://www.episkin.com/SkinEthic%20RHE
[88]
[89]
[90]
Kosten IJ, Spiekstra SW, de Gruijl TD, Gibbs S. MUTZ-3 derived Langerhans cells in human skin equivalents show differential migration and phenotypic plasticity after allergen or irritant exposure. Toxicol Appl Pharmacol 2015; 287(1): 35-42.
[http://dx.doi.org/10.1016/j.taap.2015.05.017] [PMID: 26028481]
[91]
Wufuer M, Lee G, Hur W, et al. Skin-on-a-chip model simulating inflammation, edema and drug-based treatment. Sci Rep 2016; 6: 37471.
[http://dx.doi.org/10.1038/srep37471] [PMID: 27869150]
[92]
Regulations of Nanomaterials in USA 2016. (Available from: https://www.chemsafetypro.com/Topics/USA/Regulations_of_Nanomaterials_in_USA.html
[93]
FDA. Final Guidance for Industry-Safety of Nanomaterials in Cosmetic Products (Available from: https://www.fda.gov/media/83957/download2014
[94]
Katz LM, Dewan K, Bronaugh RL. Nanotechnology in cosmetics. Food Chem Toxicol 2015; 85: 127-37.
[http://dx.doi.org/10.1016/j.fct.2015.06.020] [PMID: 26159063]
[95]
[96]
Fytianos G, Rahdar A, Kyzas GZ. Nanomaterials in Cosmetics: Recent Updates. Nanomaterials (Basel) 2020; 10(5): 979.
[http://dx.doi.org/10.3390/nano10050979] [PMID: 32443655]
[97]
Singh AV, Laux P, Luch A, et al. Review of emerging concepts in nanotoxicology: opportunities and challenges for safer nanomaterial design. Toxicol Mech Methods 2019; 29(5): 378-87.
[http://dx.doi.org/10.1080/15376516.2019.1566425] [PMID: 30636497]
[98]
SCCS Guidance on the Safety Assessment of Nanomaterials in Cosmetics 2019. (Available from: https://ec.europa.eu/health/sites/health/files/scientific_committees/consumer_safety/docs/sccs_o_233.pdf)
[99]
Regulation (EC) No 1223/2009 2009. (Available from: https://ec.europa.eu/growth/sectors/cosmetics/products/)
[100]
European Union Observatory for Nanomaterials (EUON) (Available from: https://euon.echa.europa.eu/)
[101]
[102]
Prasad M, Lambe UP, Brar B, et al. Nanotherapeutics: An insight into healthcare and multi-dimensional applications in medical sector of the modern world. Biomed Pharmacother 2018; 97: 1521-37.
[http://dx.doi.org/10.1016/j.biopha.2017.11.026] [PMID: 29793315]

© 2024 Bentham Science Publishers | Privacy Policy