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Conventional treatments are mainly based on tyrosinase inhibition; however, many depigmenting agents have limitations, including low stability, poor skin permeation, prolonged treatment durations, and adverse effects such as irritation and dermatitis. In this context, nanotechnology-based delivery systems have emerged as promising alternatives for the topical administration of depigmenting compounds. Therefore, this review discusses recent advances in nanotechnology-based strategies for treating skin hyperpigmentation, with a primary focus on lipid-based nanosystems, including liposomes, nanoemulsions, solid lipid nanoparticles, and nanostructured lipid carriers. A total of 33 studies published between 2000 and 2025 were analyzed. The reviewed studies demonstrated that nanoencapsulation may improve the physicochemical stability, enable controlled release, enhance skin permeation\/retention, and increase the therapeutic performance of depigmenting agents while reducing toxicity and adverse effects. In vitro studies also reported enhanced tyrosinase inhibition, high cell viability, and increased accumulation of active compounds in different skin layers. Overall, nanotechnology-based delivery systems represent a promising and versatile approach for improving the efficacy and safety of topical treatments for skin hyperpigmentation.<\/jats:p>","DOI":"10.31083\/pharmazie52238","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:26:12Z","timestamp":1788441972000},"source":"Crossref","is-referenced-by-count":0,"title":["Nanotechnology-Based Strategies for Treating Skin Hyperpigmentation: A Review of Current Advances and Challenges"],"prefix":"10.31083","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8245-2558","authenticated-orcid":true,"given":"Gabriela F\u00e1tima de Lima","family":"Flores","sequence":"first","affiliation":[{"name":"School of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90610-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1628-8574","authenticated-orcid":true,"given":"Gabriela Fusinatto de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90610-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1714-2062","authenticated-orcid":true,"given":"Debora Cristine Chrisostomo","family":"Dias","sequence":"additional","affiliation":[{"name":"School of Medicine, Federal University of Rio Grande (FURG), Rio Grande, RS 96203-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6854-8545","authenticated-orcid":true,"given":"Ana Paula","family":"Horn","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences, Federal University of Rio Grande (FURG), Rio Grande, RS 96203-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9198-437X","authenticated-orcid":true,"given":"Cristiana Lima","family":"Dora","sequence":"additional","affiliation":[{"name":"School of Medicine, Federal University of Rio Grande (FURG), Rio Grande, RS 96203-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1043-5855","authenticated-orcid":true,"given":"Let\u00edcia Scherer","family":"Koester","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90610-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0777-9497","authenticated-orcid":true,"given":"Fl\u00e1via Nathiely Silveira","family":"Fachel","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90610-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5808-3043","authenticated-orcid":true,"given":"Helder Ferreira","family":"Teixeira","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90610-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Lotfollahi Z. The anatomy, physiology and function of all skin layers and the impact of ageing on the skin. Wound Practice and Research. 2024; 32: 6\u201310.","DOI":"10.33235\/wpr.32.1.6-10"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Aida Maranduca M, Liliana Hurjui L, Constantin Branisteanu D, Nicolae Serban D, Elena Branisteanu D, Dima N, et al. Skin - a vast organ with immunological function (Review). Experimental and Therapeutic Medicine. 2020; 20: 18\u201323.","DOI":"10.3892\/etm.2020.8619"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Lipsker D, Lenormand C. Hyperpigmentation. Annales De Dermatologie et De Venereologie. 2019; 146: 666\u2013682.","DOI":"10.1016\/j.annder.2019.05.005"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Shao W, Ren H, Yin M, Li X, Zhang F, Wang X, et al. Enhanced stability and reduced irritation of 4-n-butylresorcinol via nanoemulsion formulation: Implications for skin pigmentation treatment. European Journal of Medicinal Chemistry. 2024; 279: 116867.","DOI":"10.1016\/j.ejmech.2024.116867"},{"key":"ref5","unstructured":"Martel JL, Miao JH, Badri T, Fakoya AO. Anatomy, Hair Follicle. 2024. Available at: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470321\/ (Accessed: 13 June 2026)."},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Bento-Lopes L, Caba\u00e7o LC, Charneca J, Neto MV, Seabra MC, Barral DC. Melanin's Journey from Melanocytes to Keratinocytes: Uncovering the Molecular Mechanisms of Melanin Transfer and Processing. International Journal of Molecular Sciences. 2023; 24: 11289.","DOI":"10.3390\/ijms241411289"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Pawlina W, Ross MH. A Text and Atlas: With Correlated Cell and Molecular Biology. Morphologia. 2019; 13: 76\u201389.","DOI":"10.26641\/1997-9665.2019.4.76-89"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Kapoor R, Dhatwalia SK, Kumar R, Rani S, Parsad D. 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The natural-based optimization of kojic acid conjugated to different thio-quinazolinones as potential anti-melanogenesis agents with tyrosinase inhibitory activity. Bioorganic & Medicinal Chemistry. 2021; 36: 116044.","DOI":"10.1016\/j.bmc.2021.116044"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Cichorek M, Wachulska M, Stasiewicz A, Tymi\u0144ska A. Skin melanocytes: biology and development. Postepy Dermatologii i Alergologii. 2013; 30: 30\u201341.","DOI":"10.5114\/pdia.2013.33376"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Gillbro JM, Olsson MJ. The melanogenesis and mechanisms of skin-lightening agents--existing and new approaches. International Journal of Cosmetic Science. 2011; 33: 210\u2013221.","DOI":"10.1111\/j.1468-2494.2010.00616.x"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Kim YJ, Uyama H. Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and perspective for the future. Cellular and Molecular Life Sciences: CMLS. 2005; 62: 1707\u20131723.","DOI":"10.1007\/s00018-005-5054-y"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Bae-Harboe YSC, Park HY. Tyrosinase: a central regulatory protein for cutaneous pigmentation. The Journal of Investigative Dermatology. 2012; 132: 2678\u20132680.","DOI":"10.1038\/jid.2012.324"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Tang HC, Chen YC. Identification of tyrosinase inhibitors from traditional Chinese medicines for the management of hyperpigmentation. SpringerPlus. 2015; 4: 184.","DOI":"10.1186\/s40064-015-0956-0"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Homma T, Kageyama S, Nishikawa A, Nagata K. Anti-melanogenic activity of salacinol by inhibition of tyrosinase oligosaccharide processing. Journal of Biochemistry. 2020; 167: 503\u2013511.","DOI":"10.1093\/jb\/mvz115"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Bastonini E, Kovacs D, Picardo M. Skin Pigmentation and Pigmentary Disorders: Focus on Epidermal\/Dermal Cross-Talk. Annals of Dermatology. 2016; 28: 279\u2013289.","DOI":"10.5021\/ad.2016.28.3.279"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Slominski A, Wortsman J, Plonka PM, Schallreuter KU, Paus R, Tobin DJ. Hair follicle pigmentation. The Journal of Investigative Dermatology. 2005; 124: 13\u201321.","DOI":"10.1111\/j.0022-202X.2004.23528.x"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Lin JY, Fisher DE. Melanocyte biology and skin pigmentation. Nature. 2007; 445: 843\u2013850.","DOI":"10.1038\/nature05660"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Murase D, Hachiya A, Takano K, Hicks R, Visscher MO, Kitahara T, et al. Autophagy has a significant role in determining skin color by regulating melanosome degradation in keratinocytes. The Journal of Investigative Dermatology. 2013; 133: 2416\u20132424.","DOI":"10.1038\/jid.2013.165"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Xing X, Dan Y, Xu Z, Xiang L. Implications of Oxidative Stress in the Pathogenesis and Treatment of Hyperpigmentation Disorders. Oxidative Medicine and Cellular Longevity. 2022; 2022: 7881717.","DOI":"10.1155\/2022\/7881717"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Wang F, Ma W, Fan D, Hu J, An X, Wang Z. The biochemistry of melanogenesis: an insight into the function and mechanism of melanogenesis-related proteins. Frontiers in Molecular Biosciences. 2024; 11: 1440187.","DOI":"10.3389\/fmolb.2024.1440187"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Moolla S, Miller-Monthrope Y. Dermatology: how to manage facial hyperpigmentation in skin of colour. Drugs in Context. 2022; 11: 1\u201314.","DOI":"10.7573\/dic.2021-11-2"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Nomakhosi M, Heidi A. Natural options for management of melasma, a review. Journal of Cosmetic and Laser Therapy: Official Publication of the European Society for Laser Dermatology. 2018; 20: 470\u2013481.","DOI":"10.1080\/14764172.2018.1427874"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Ortonne JP, Bissett DL. Latest insights into skin hyperpigmentation. The Journal of Investigative Dermatology. Symposium Proceedings. 2008; 13: 10\u201314.","DOI":"10.1038\/jidsymp.2008.7"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Dai NT, Chang HI, Wang YW, Fu KY, Huang TC, Huang NC, et al. Restoration of skin pigmentation after deep partial or full-thickness burn injury. Advanced Drug Delivery Reviews. 2018; 123: 155\u2013164.","DOI":"10.1016\/j.addr.2017.10.010"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Ke MS, Soriano T, Lask GP. Optimal treatments for hyperpigmentation. Journal of Cosmetic and Laser Therapy: Official Publication of the European Society for Laser Dermatology. 2006; 8: 7\u201313.","DOI":"10.1080\/14764170600620668"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Grayson C, Heath CR. Dupilumab Improves Atopic Dermatitis and Post-Inflammatory Hyperpigmentation in Patient With Skin of Color. Journal of Drugs in Dermatology: JDD. 2020; 19: 776\u2013778.","DOI":"10.36849\/JDD.2020.4937"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Sarkar R, Parmar NV, Kapoor S. Treatment of Postinflammatory Hyperpigmentation With a Combination of Glycolic Acid Peels and a Topical Regimen in Dark-Skinned Patients: A Comparative Study. Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]. 2017; 43: 566\u2013573.","DOI":"10.1097\/DSS.0000000000001007"},{"key":"ref46","unstructured":"Camayo TV, Lee VR, Zhou XA. Drug-Induced Pigmentation. 2026. Available at: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK542253\/ (Acessed: 19 November 2024)"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Afrin A, Cohen PR. Doxycycline-Associated Hyperpigmentation: A Case Report and Literature Review. Cureus. 2022; 14: e23754.","DOI":"10.7759\/cureus.23754"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Miot LDB, Miot HA, Silva MGD, Marques MEA. Physiopathology of melasma. Anais Brasileiros De Dermatologia. 2009; 84: 623\u2013635.","DOI":"10.1590\/s0365-05962009000600008"},{"key":"ref49","doi-asserted-by":"crossref","unstructured":"Puri N, Gill SK, Kumar S, Brar BK, Chahal A. A study of dermoscopy in patients of melasma in a tertiary care centre in North India. Pigment International. 2022; 9: 176\u2013181.","DOI":"10.4103\/pigmentinternational.pigmentinternational_84_20"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"Han HJ, Kim JC, Park YJ, Kang HY. Targeting the dermis for melasma maintenance treatment. Scientific Reports. 2024; 14: 949.","DOI":"10.1038\/s41598-023-51133-w"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"Duval C, Bourreau E, Warrick E, Bastien P, Nouveau S, Bernerd F. A chronic pro-inflammatory environment contributes to the physiopathology of actinic lentigines. Scientific Reports. 2024; 14: 5256.","DOI":"10.1038\/s41598-024-53990-5"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"Jung JM, Yang H, Lee WJ, Won CH, Lee MW, Choi JH, et al. Inflammatory features and rete ridge patterns of facial solar lentigo may guide laser treatment. Dermatologic Therapy. 2020; 33: e13464.","DOI":"10.1111\/dth.13464"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"Rendon M, Horwitz S. Topical treatment of hyperpigmentation disorders. Annales De Dermatologie et De Venereologie. 2012; 139 Suppl 4: S153\u2013S158.","DOI":"10.1016\/S0151-9638(12)70128-X"},{"key":"ref54","unstructured":"Davis EC, Callender VD. Postinflammatory hyperpigmentation: a review of the epidemiology, clinical features, and treatment options in skin of color. The Journal of Clinical and Aesthetic Dermatology. 2010; 3: 20\u201331."},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"Kanlayavattanakul M, Chongnativisit W, Chaikul P, Lourith N. Phenolic-rich Pomegranate Peel Extract: In Vitro, Cellular, and In Vivo Activities for Skin Hyperpigmentation Treatment. Planta Medica. 2020; 86: 749\u2013759.","DOI":"10.1055\/a-1170-7785"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"Zaidi KU, Ali SA, Ali A, Naaz I. Natural Tyrosinase Inhibitors: Role of Herbals in the Treatment of Hyperpigmentary Disorders. 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Antioxidants (Basel, Switzerland). 2021; 10: 436.","DOI":"10.3390\/antiox10030436"},{"key":"ref77","doi-asserted-by":"publisher","unstructured":"Talele P, Jadhav A, Tayade S, Sahu S, Sharma KK, Shimpi N. Hydroquinone loaded solid lipid nanoparticles comprised of stearic acid and ionic emulsifiers: Physicochemical characterization and in vitro release study. Journal of Molecular Liquids. 2022; 368: 120590.","DOI":"10.1016\/j.molliq.2022.120590"},{"key":"ref78","doi-asserted-by":"publisher","unstructured":"Nautiyal A, Wairkar S. A reduced dose of Azelaic acid-loaded solid lipid nanoparticles for treatment of hyperpigmentation: In vitro characterization and cell line studies. Journal of Drug Delivery Science and Technology. 2023; 80: 104158.","DOI":"10.1016\/j.jddst.2023.104158"},{"key":"ref79","doi-asserted-by":"publisher","unstructured":"Ghanbarzadeh S, Hariri R, Kouhsoltani M, Shokri J, Javadzadeh Y, Hamishehkar H. 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Drug Development and Industrial Pharmacy. 2019; 45: 642\u2013650.","DOI":"10.1080\/03639045.2019.1569032"},{"key":"ref85","doi-asserted-by":"publisher","unstructured":"Duarah S, Durai RD, Narayanan VB. Nanoparticle-in-gel system for delivery of vitamin C for topical application. Drug Delivery and Translational Research. 2017; 7: 750\u2013760.","DOI":"10.1007\/s13346-017-0398-z"},{"key":"ref86","doi-asserted-by":"publisher","unstructured":"Tanveer N, Khan HMS, Akhtar N. Whitening effect of kojic acid dipalmitate loaded nanosized ethosomal gel for the treatment of hyperpigmentation: In vitro and in vivo characterization. Journal of Cosmetic Dermatology. 2022; 21: 6850\u20136862.","DOI":"10.1111\/jocd.15408"},{"key":"ref87","doi-asserted-by":"publisher","unstructured":"Jamadar AT, Peram MR, Chandrasekhar N, Kanshide A, Kumbar VM, Diwan PV. Formulation, Optimization, and Evaluation of Ultradeformable Nanovesicles for Effective Topical Delivery of Hydroquinone. Journal of Pharmaceutical Innovation. 2023; 18: 506\u2013524.","DOI":"10.1007\/s12247-022-09657-7"},{"key":"ref88","doi-asserted-by":"publisher","unstructured":"Chang NF, Wu PS, Yang HJ, Zheng YM, Lin CC. Preparation and Evaluation of Nanoemulsion Formulation Containing Kojic Acid and Kojyl 3-aminopropylphosphonic Acid. Current Pharmaceutical Biotechnology. 2025; 26: 608\u2013616.","DOI":"10.2174\/0113892010310230240615112928"},{"key":"ref89","doi-asserted-by":"publisher","unstructured":"Kumar A, Rao R. Enhancing efficacy and safety of azelaic acid via encapsulation in cyclodextrin nanosponges: development, characterization and evaluation. Polymer Bulletin. 2021; 78: 5275\u20135302.","DOI":"10.1007\/s00289-020-03366-2"},{"key":"ref90","doi-asserted-by":"publisher","unstructured":"Farooqui RK, Kaurav M, Kumar M, Sudheesh MS, Pandey RS. Permeation enhancer nanovesicles mediated topical delivery of curcumin for the treatment of hyperpigmentation. Journal of Liposome Research. 2022; 32: 332\u2013339.","DOI":"10.1080\/08982104.2021.2024567"},{"key":"ref91","doi-asserted-by":"publisher","unstructured":"Inal O, Amasya G, Sezgin Bayindir Z, Yuksel N. Development and quality assessment of glutathione tripeptide loaded niosome containing carbopol emulgels as nanocosmeceutical formulations. International Journal of Biological Macromolecules. 2023; 241: 124651.","DOI":"10.1016\/j.ijbiomac.2023.124651"},{"key":"ref92","doi-asserted-by":"publisher","unstructured":"Souto EB, Cano A, Martins-Gomes C, Coutinho TE, Zieli\u0144ska A, Silva AM. Microemulsions and Nanoemulsions in Skin Drug Delivery. Bioengineering (Basel, Switzerland). 2022; 9: 158.","DOI":"10.3390\/bioengineering9040158"},{"key":"ref93","doi-asserted-by":"publisher","unstructured":"Shah AA, Kehinde EO, Patel J. An Emerging Era for Targeted Drug Delivery: Nanosponges. Journal of Pharmaceutical Research International. 2021; 33: 153\u2013160.","DOI":"10.9734\/jpri\/2021\/v33i31B31703"},{"key":"ref94","doi-asserted-by":"publisher","unstructured":"Queiroz MD, Muehlmann LA. Characteristics and Preparation of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers. Journal of Nanotheranostics. 2024; 5: 188\u2013211.","DOI":"10.3390\/jnt5040012"},{"key":"ref95","doi-asserted-by":"publisher","unstructured":"Touitou E, Natsheh H. The Evolution of Emerging Nanovesicle Technologies for Enhanced Delivery of Molecules into and across the Skin. Pharmaceutics. 2024; 16: 267.","DOI":"10.3390\/pharmaceutics16020267"},{"key":"ref96","doi-asserted-by":"publisher","unstructured":"Choudhury A, Kirti A, Lenka SS, Naser SS, Sinha A, Kumari S, et al. Strategic advances in liposomes technology: translational paradigm in transdermal delivery for skin dermatosis. Journal of Nanobiotechnology. 2025; 23: 576.","DOI":"10.1186\/s12951-025-03660-z"},{"key":"ref97","doi-asserted-by":"publisher","unstructured":"Sguizzato M, Esposito E, Cortesi R. Lipid-Based Nanosystems as a Tool to Overcome Skin Barrier. International Journal of Molecular Sciences. 2021; 22: 8319.","DOI":"10.3390\/ijms22158319"},{"key":"ref98","doi-asserted-by":"publisher","unstructured":"Joyce P, Allen CJ, Alonso MJ, Ashford M, Bradbury MS, Germain M, et al. A translational framework to DELIVER nanomedicines to the clinic. Nature Nanotechnology. 2024; 19: 1597\u20131611.","DOI":"10.1038\/s41565-024-01754-7"},{"key":"ref99","unstructured":"Yong KN, Youngjae K, Changsoo K, Yejn P, inventor; NUMAIS CO LTD, assignee. Composition For Skin Whitening Comprising Nanovesicles. South Korea KR20220155224 (A). November. 22 November 2022."},{"key":"ref100","unstructured":"Paithankar D, inventor; SEBACIA INC, assignee. Methods Of Treating Skin Conditions Using Plasmonic Nanoparticles. China CN108430431 (A). August. 21 August 2018."},{"key":"ref101","unstructured":"Zheng Q, Cao Y, Zhang Z, inventor; Zhang Z, assignee. Nano preparation for treating pigmentation diseases and preparation method of nano preparation. China CN112107600 (A). December. 22 December 2020."},{"key":"ref102","unstructured":"Yen RCK, inventor; Yen RCK, PTLNV LLC SERIES FOUR 4, assignee. Nanoparticles for the therapeutic treatment of radiation-induced skin ulcers. United States of America US2019328844 (A1). October. 31 October 2019."},{"key":"ref103","unstructured":"Zhou Y, inventor; FOSHAN CITY CHANCHENG DISTR RELA SPACE BIOTECHNOLOGY CO LTD, assignee. Preparation method of plant compound skin-whitening agent nano particles. China CN108714131 (A). October. 30 October 2018."},{"key":"ref104","unstructured":"Park SC, J BK, Lee TH, Ko YT, Moh SH, Baek SH, et al., inventor; UNIV GACHON IND ACAD COOP FOUND, REPUBLIC KOREA MAN RURAL DEV, assignee. Composition For Skin-Whitening Comprising Nanoparticle Of Callus Derived From Resveratrol-Enriched Rice. South Korea KR20160029979 (A). March. 16 March 2016."},{"key":"ref105","unstructured":"Li Z, inventor; LVEN ZEYA GROUP CO LTD, assignee. Whitening nano-composition targeting fibroblasts and melanocytes as well as preparation method and application of whitening nano-composition. China CN116531271 (A). August. 4 August 2023."},{"key":"ref106","unstructured":"Lee S K, Urabe T, Choi CH, Chae YS, Woo JW, Lee JS, inventor; Choi CH, JE MA YU CO LTD, KIMIWA CO LTD, assignee. Skin Bleaching Composition Including Nanopolisome Involving Horse Oil And Horse Placenta Extract, And Method For Producing Water- Soluble Nanoliposome. Japan JP2010215605 (A). 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