Introduction: When the skin’s integrity is compromised, one or more of its safeguarding mechanisms can be impaired. In this line of thought, wound healing often requires topical delivery of active pharmaceutical ingredients (APIs) to ensure proper skin regeneration. Unfortunately, the dermal route of administration has drawbacks in terms of insufficient drug penetration and low bioavailability. The employment of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) in this field could be a promising approach due to their ability to increase drug permeation and provide sustained release and targeted delivery.Aim: This review aims to provide an update on the use of SLNs and NLCs in wound management and contribute to the advancement of innovative and effective treatments.Materials and Methods: Systematic research was conducted in various databases to identify relevant scientific publications on the use of lipid nanoparticles (LNPs) as drug delivery systems for topical wound care.Results and Conclusion: Lipid nanoparticles, including SLNs and NLCs, have been extensively investigated as delivery platforms for a wide range of compounds in wound healing. The encapsulation of synthetic, semi-synthetic, and natural molecules within these lipid-based nanosystems has demonstrated promising outcomes such as enhanced anti-inflammatory and antimicrobial effects, as well as improved wound healing, leading to faster regeneration and increased tear resistance. Overall, lipid nanoparticles offer a valuable strategy for wound management with the potential to revolutionize the field and offer improved therapeutic options for better patient outcomes. 1. Romanovsky AA. Skin temperature: its role in thermoregulation. Acta Physiol. 2014;210(3):498-507. doi: 10.1111/apha.12231. 2. Nguyen AV, Soulika AM. The dynamics of the skin's immune system. Int J Mol Sci. 2019;20(8):1811. doi: 10.3390/ijms20081811. 3. Eyerich S, Eyerich K, Traidl-Hoffmann C, Biedermann T. Cutaneous barriers and skin immunity: differentiating a connected network. Trends Immunol. 2018;39(4):315-27. doi: 10.1016/j.it.2018.02.004. 4. Quaresma JAS. Organization of the skin immune system and compartmentalized immune responses in infectious diseases. Clin Microbiol Rev. 2019;32(4):e00034-18. doi: 10.1128/CMR.00034-18. 5. Trucillo P, Di Maio E. Classification and production of polymeric foams among the systems for wound treatment. Polymers. 2021;13(10):1608.doi: 10.3390/polym13101608. 6. Subramaniam T, Fauzi MB, Lokanathan Y, Law JX. The role of calcium in wound healing. Int J Mol Sci. 2021;22(12):6486. doi: 10.3390/ijms22126486. 7. Grandi V, Corsi A, Pimpinelli N, Bacci S. Cellular mechanisms in acute and chronic wounds after PDT therapy: an update. Biomedicines. 2022;10(7):1624. doi: 10.3390/biomedicines10071624. 8. Criollo-Mendoza MS, Contreras-Angulo LA, Leyva-López N, Gutiérrez-Grijalva EP, Jiménez-Ortega LA, Heredia JB. Wound healing properties of natural products: mechanisms of action. Molecules. 2023;28(2):598. doi: 10.3390/molecules28020598. 9. Sharma D, Srivastava S, Kumar S, Sharma PK, Hassani R, Dailah HG, et al. Biodegradable electrospun scaffolds as an emerging tool for skin wound regeneration: a comprehensive review. Pharmaceuticals. 2023;16(2):325. doi: 10.3390/ph16020325. 10. Pârvănescu (Pană) RD, Watz C-G, Moacă E-A, Vlaia L, Marcovici I, Macașoi IG, et al. Oleogel formulations for the topical delivery of betulin and lupeol in skin injuries—preparation, physicochemical characterization, and pharmaco-toxicological evaluation. Molecules. 2021;26(14):4174. doi: 10.3390/molecules26144174. 11. Raziyeva K, Kim Y, Zharkinbekov Z, Kassymbek K, Jimi S, Saparov A. Immunology of acute and chronic wound healing. Biomolecules. 2021;11(5):700. doi: 10.3390/biom11050700. 12. Wang W, Lu KJ, Yu CH, Huang QL, Du YZ. Nano-drug delivery systems in wound treatment and skin regeneration. J Nanobiotechnology. 2019;17(1):82. doi: 10.1186/s12951-019-0514-y. 13. de Souza ML, Dos Santos WM, de Sousa ALMD, de Albuquerque Wanderley Sales V, Nóbrega FP, de Oliveira MVG, et al. Lipid nanoparticles as a skin wound healing drug delivery system: discoveries and advances. Curr Pharm Des. 2020;26(36):4536-50. doi: 10.2174/1381612826666200417144530. 14. Javadzadeh Y, Azharshekoufeh Bahari L. Therapeutic nanostructures for dermal and transdermal drug delivery. In: Grumezescu AM, editor. Nano- and microscale drug delivery systems. Amsterdam: Elsevier; 2017. p. 131-46. 15. Müller RH, Radtke M, Wissing SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev. 2002;54 suppl 1:S131-55. doi: 10.1016/s0169-409x(02)00118-7. 16. Cavalli R, Gasco MR, Chetoni P, Burgalassi S, Saettone MF. Solid lipid nanoparticles (SLN) as ocular delivery system for tobramycin. Int J Pharm. 2002;238(1-2):241-5. doi: 10.1016/s0378-5173(02)00080-7. 17. Matei A-M, Caruntu C, Tampa M, Georgescu SR, Matei C, Constantin MM, et al. Applications of nanosized-lipid-based drug delivery systems in wound care. Appl Sci. 2021;11(11):4915. doi: 10.3390/app11114915. 18. Ghasemiyeh P, Mohammadi-Samani S. Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications, advantages and disadvantages. Res Pharm Sci. 2018;13(4):288-303. doi: 10.4103/1735-5362.235156. 19. Barroso A, Mestre H, Ascenso A, Simões S, Reis C. Nanomaterials in wound healing: From material sciences to wound healing applications. Nano Select. 2020;1(5):443-60. doi: 10.1002/nano.202000055. 20. Andonova V, Peneva P. Characterization methods for solid lipid nanoparticles (sln) and nanostructured lipid carriers (NLC). Curr Pharm Des. 2017;23:6630-42. doi: 10.2174/1381612823666171115105721. 21. Musielak E, Feliczak-Guzik A, Nowak I. Synthesis and potential applications of lipid nanoparticles in medicine. Materials. 2022;15(2):682. doi: 10.3390/ma15020682. 22. Eh Suk VR, Mohd Latif F, Teo YY, Misran M. Development of nanostructured lipid carrier (NLC) assisted with polysorbate nonionic surfactants as a carrier for l-ascorbic acid and Gold Tri.E 30. J Food Sci Technol. 2020;57(9):3259-66. doi: 10.1007/s13197-020-04357-x. 23. Silva AM, Martins-Gomes C, Coutinho TE, Fangueiro JF, Sanchez-Lopez E, Pashirova TN, et al. Soft cationic nanoparticles for drug delivery: production and cytotoxicity of solid lipid nanoparticles (SLNs). Appl Sci. 2019;9(20):4438. doi:10.3390/app9204438. 24. Bose S, Du Y, Takhistov P, Michniak-Kohn B. Formulation optimization and topical delivery of quercetin from solid lipid based nanosystems. Int J Pharm. 2013;441(1-2):56-66. doi: 10.1016/j.ijpharm.2012.12.013. 25. Balamurugan K, Chintamani P. Lipid nano particulate drug delivery: An overview of the emerging trend. Pharma Innov. 2018;7(7):779-89. 26. Dhiman N, Awasthi R, Sharma B, Kharkwal H, Kulkarni GT. Lipid nanoparticles as carriers for bioactive delivery. Front Chem. 2021;9:580118. doi: 10.3389/fchem.2021.580118. 27. Sotirova Y, Stoeva S, Nikolova R, Andonova V. Nanostructured lipid carriers as a promising dermal delivery platform for St. John’s wort extract: preliminary studies. J IMAB. 2023;29:4911-9. doi:10.5272/jimab.2023292.4911. 28. Luan L, Chi Z, Liu C. Chinese white wax solid lipid nanoparticles as a novel nanocarrier of curcumin for inhibiting the formation of Staphylococcus aureus Biofilms. Nanomaterials. 2019;9(5):763. doi: 10.3390/nano9050763. 29. Lerata MS, D’Souza S, Sibuyi NRS, Dube A, Meyer M, Samaai T, et al. Encapsulation of variabilin in stearic acid solid lipid nanoparticles enhances its anticancer activity in vitro. Molecules. 2020;25(4):830. doi: 10.3390/molecules25040830. 30. D’Souza AA, Shegokar R. Potential of oils in the development of nanostructured lipid carriers. In: Rai M, Zacchino S, Derita M, editors. Essential oils and nanotechnology for treatment of microbial diseases. Boca Raton: CRC Press; 2017. p. 242-57. 31. Basso J, Mendes M, Cova T, Sousa J, Pais A, Fortuna A, et al. A stepwise framework for the systematic development of lipid nanoparticles. Biomolecules. 2022;12(2):223. doi: 10.3390/biom12020223. 32. Singh AK, Mukerjee A, Pandey H, Mishra SB. Fabrication of solid lipid nanoparticles by hot high shear homogenization and optimization by Box–Behnken design: An accelerated stability assessment. J Appl Pharm Sci, 2021;11(9):35-47. doi: 10.7324/JAPS.2021.110905 33. Kim CH, Kim BD, Lee TH, Kim HK, Lyu MJ, Yoon YI, et al. Synergistic co-administration of docetaxel and curcumin to chemoresistant cancer cells using PEGylated and RIPL peptide-conjugated nanostructured lipid carriers. Cancer Nano. 2022;13:17. 34. Dhillon P, Mirza MA, Anwer MK, Alshetaili AS, Alshahrani SM, Iqbal Z. Development and optimization of erythromycin-loaded lipid-based gel by Taguchi design: In vitro characterization and antimicrobial evaluation. Braz J Pharm Sci. 2019;55:e17395. doi: 10.1590/s2175-97902019000217395. 35. Karami MA, Sharif Makhmal Zadeh B, Koochak M, Moghimipur E. Superoxide dismutase-loaded solid lipid nanoparticles prepared by cold homogenization method: characterization and permeation study through burned rat skin. Jundishapur J Nat Pharm Prod. 2016;11(4):e33968. doi: 10.17795/jjnpp-33968. 36. Salminen H, Kasapoğlu KN, Özçelik B, Weiss J. Stabilization of solid lipid nanoparticles with glycyrrhizin. Eur Food Res Technol. 2023;249(2):787-98. doi:10.1007/s00217-022-04176-8. 37. Chakravarty P, Famili A, Nagapudi K, Al-Sayah MA. Using supercritical fluid technology as a green alternative during the preparation of drug delivery systems. Pharmaceutics. 2019;11(12):629. doi: 10.3390/pharmaceutics11120629. 38. Winarti L, Suwaldi S, Martien R, Hakim L. Formulation of self-nanoemulsifying drug delivery system of bovine serum albumin using HLB (hydrophilic-lypophilic balance) approach. Indones J Pharm. 2016;27:117-27. doi:10.14499/indonesianjpharm27iss3pp117. 39. Shimojo AAM, Fernandes ARV, Ferreira NRE, Sanchez-Lopez E, Santana MHA, Souto EB. Evaluation of the influence of process parameters on the properties of resveratrol-loaded NLC using 22 full factorial design. Antioxidants. 2019;8(8):272. doi: 10.3390/antiox8080272. 40. Akanda M, Getti G, Douroumis D. In vivo evaluation of nanostructured lipid carrier systems (NLCs) in mice bearing prostate cancer tumours. Drug Deliv Transl Res. 2023;13(8):2083-95. doi: 10.1007/s13346-021-01095-1. Epub 2021 Nov 29. 41. Vicente-Pascual M, Gómez-Aguado I, Rodríguez-Castejón J, Rodríguez-Gascón A, Muntoni E, Battaglia L, et al. Topical administration of SLN-based gene therapy for the treatment of corneal inflammation by de novo IL-10 production. Pharmaceutics. 2020;12(6):584. doi: 10.3390/pharmaceutics12060584. 42. Chaiyana W, Anuchapreeda S, Somwongin S, Marsup P, Lee KH, Lin WC, et al. Dermal delivery enhancement of natural anti-ageing compounds from Ocimum sanctum Linn. extract by nanostructured lipid carriers. Pharmaceutics. 2020;12(4):309. doi: 10.3390/pharmaceutics12040309. 43. Moglad EH, Fatima F, Ahmed MM, Seshadri VD, Anwer MK, Aldawsari MF. Development of topical antibacterial gel loaded with cefadroxil solid lipid nanoparticles: in vivo wound healing activity and epithelialization study. Int J Pharmacol. 2020;16:298-309. 44. Mastiholimath VS, Valerie CTW, Mannur VS, Dandagi PM, Gadad AP, Khanal P. Formulation and evaluation of solid lipid nanoparticle containing silver sulfadiazine for second and third degree burn wounds and its suitable analytical method development and validation. Indian J Pharm Educ Res. 2019;54(1):31-45. doi:10.5530/ijper.54.1.5. 45. El-Salamouni NS, Gowayed MA, Seiffein NL, Abdel-Moneim RA, Kamel MA, Labib GS. Valsartan solid lipid nanoparticles integrated hydrogel: A challenging repurposed use in the treatment of diabetic foot ulcer, in-vitro/in-vivo experimental study. Int J Pharm. 2021;592:120091. doi: 10.1016/j.ijpharm.2020.120091. 46. Gupta B, Sharma G, Sharma P, Sandhu SK, Kaur IP. Self-gelling solid lipid nanoparticle hydrogel containing simvastatin as suitable wound dressing: an investigative study. Gels. 2022;8(1):58. doi: 10.3390/gels8010058. 47. Ahmadi M, Mehdikhani M, Varshosaz J, Farsaei S, Torabi H. Pharmaceutical evaluation of atorvastatin-loaded nanostructured lipid carriers incorporated into the gelatin/hyaluronic acid/polycaprolactone scaffold for the skin tissue engineering. J Biomater Appl. 2021;35(8):958-77. doi: 10.1177/0885328220970760. 48. Natarajan J, Sanapalli BKR, Bano M, Singh SK, Gulati M, Karri VVSR. Nanostructured lipid carriers of pioglitazone loaded collagen/chitosan composite scaffold for diabetic wound healing. Adv Wound Care. 2019;8(10):499-513. doi: 10.1089/wound.2018.0831. 49. Motawea A, Abd El-Gawad AEH, Borg T, Motawea M, Tarshoby M. The impact of topical phenytoin loaded nanostructured lipid carriers in diabetic foot ulceration. Foot. 2019;40:14-21. doi: 10.1016/j.foot.2019.03.007.50. Varrica C, Carvalheiro M, Faria-Silva C, Eleutério C, Sandri G, Simões S. Topical allopurinol-loaded nanostructured lipid carriers: a novel approach for wound healing management. Bioengineering. 2021;8(12):192. doi: 10.3390/bioengineering8120192. 51. Romić MD, Sušac A, Lovrić J, Cetina-Čižmek B, Filipović-Grčić J, Hafner A. Evaluation of stability and in vitro wound healing potential of melatonin loaded (lipid enriched) chitosan based microspheres. Acta Pharm. 2019;69(4):635-48. doi: 10.2478/acph-2019-0049. 52. Kakkar V, Kaur IP, Kaur AP, Saini K, Singh KK. Topical delivery of tetrahydrocurcumin lipid nanoparticles effectively inhibits skin inflammation: in vitro and in vivo study. Drug Dev Ind Pharm. 2018;44(10):1701-12. doi: 10.1080/03639045.2018.1492607. 53. Kumar, SCS. Solid lipid nanoparticles containing asiaticoside: development of topical delivery formulation. RGUHS J Pharm Sci. 2018;8(2):32-44. doi: 10.5530/rjps.2018.2.1. 54. Arantes VT, Faraco AAG, Ferreira FB, Oliveira CA, Martins-Santos E, Cassini-Vieira P, et al. Retinoic acid-loaded solid lipid nanoparticles surrounded by chitosan film support diabetic wound healing in in vivo study. Colloids Surf B Biointerfaces. 2020;188:110749. doi: 10.1016/j.colsurfb.2019.110749. 55. Reczyńska-Kolman K, Hartman K, Kwiecień K, Brzychczy-Włoch M, Pamuła E. Composites based on gellan gum, alginate and nisin-enriched lipid nanoparticles for the treatment of infected wounds. Int J Mol Sci. 2021;23(1):321. doi: 10.3390/ijms23010321. 56. Ryan A, Patel P, Ratrey P, O’Connor PM, O’Sullivan J, Ross RP, et al. The development of a solid lipid nanoparticle (SLN)-based lacticin 3147 hydrogel for the treatment of wound infections. Drug Deliv Transl Res. 2023;13(9):2407-23. doi: 10.1007/s13346-023-01332-9. 57. Albaayit SFA, Rasedee A, Abdullah N. Zerumbone-loaded nanostructured lipid carrier gel facilitates wound healing in rats. Rev Bras Farmacogn. 2020;30:272-8. oi: 10.1155/2022/1129297. 58. Sun D, Guo S-Y, Yang L, Wang Y-R, Wei X-H, Song S, et al. Silicone elastomer gel impregnated with 20(S)-protopanaxadiol-loaded nanostructured lipid carriers for ordered diabetic ulcer recovery. Acta Pharmacol Sin. 2020;41(1):119-28. doi: 10.1038/s41401-019-0288-7. 59. Alexander HR, Syed Alwi SS, Yazan LS, Zakarial Ansar FH, Ong YS. Migration and proliferation effects of thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) and thymoquinone (TQ) on in vitro wound healing models. Evid Based Complement Alternat Med. 2019;2019:9725738. doi: 10.1155/2019/9725738. 60. Sharifi-Rad J, Sureda A, Tenore GC, Daglia M, Sharifi-Rad M, Valussi M, et al. Biological activities of essential oils: from plant chemoecology to traditional healing systems. Molecules. 2017;22(1):70. doi: 10.3390/molecules22010070. 61. Sousa VI, Parente JF, Marques JF, Forte MA, Tavares CJ. Microencapsulation of essential oils: a review. Polymers. 2022;14(9):1730. doi: 10.3390/polym14091730. 62. Cimino C, Maurel OM, Musumeci T, Bonaccorso A, Drago F, Souto EMB, et al. Essential oils: pharmaceutical applications and encapsulation strategies into lipid-based delivery systems. Pharmaceutics. 2021;13(3):327. doi: 10.3390/pharmaceutics13030327. 63. Kamel R, Afifi SM, Abdou AM, Esatbeyoglu T, AbouSamra MM. Nanolipogel loaded with tea tree oil for the management of burn: GC-MS analysis, in vitro and in vivo evaluation. Molecules. 2022;27(19):6143. doi: 10.3390/molecules27196143. 64. Gad HA, Abd El-Rahman FA, Hamdy GM. Chamomile oil loaded solid lipid nanoparticles: A naturally formulated remedy to enhance the wound healing. J Drug Deliv Sci Technol. 2019;50:329-38. doi: 10.1016/j.jddst.2019.01.008. 65. Valizadeh A, Abdollahi A, Ranjbar N, Kelidari HR, Sereshti H, Osanloo M. Antibacterial effects of impregnated scaffolds with solid lipid nanoparticles gels containing three essential oils against standard and clinical strains of Pseudomonas aeruginosa and Staphylococcus aureus. Nanomed Res J. 2021;6(3):218-27. doi: 10.22034/NMRJ.2021.03.002. 66. Khezri K, Farahpour MR, Mounesi Rad S. Efficacy of Mentha pulegium essential oil encapsulated into nanostructured lipid carriers as an in vitro antibacterial and infected wound healing agent. Colloids Surf A Physicochem Eng Asp. 2020;589:124414. doi: 10.1016/j.colsurfa.2020.124414. 67. Ghodrati M, Farahpour M. Encapsulation of Peppermint essential oil in nanostructured lipid carriers: In-vitro antibacterial activity and accelerative effect on infected wound healing. Colloids Surf A Physicochem Eng Asp. 2019;564:161-9. 68. Khezri K, Farahpour MR, Mounesi Rad S. Accelerated infected wound healing by topical application of encapsulated Rosemary essential oil into nanostructured lipid carriers. Artif Cells Nanomed Biotechnol. 2019;47(1):980-8. doi: 10.1080/21691401.2019.1582539. 69. Tazehjani DAJ, Farahpour MR, Hamishehkar H. Effectiveness of topical caraway essential oil loaded into nanostructured lipid carrier as a promising platform for the treatment of infected wounds. Colloids Surf A Physicochem Eng Asp. 2020;610:125748. doi: 10.1016/j.colsurfa.2020.125748. 70. Vijayanand P, Jyothi V, Mounika A. Hibiscus rosa sinensis loaded solid lipid nanoparticles and in vivo wound healing activity in wistar albino rats. Int J Curr Pharm Res. 2020;12:78-83. doi:10.22159/ijcpr.2020v12i3.38311. 71. Sotirova Y, Gugleva V, Stoeva S, Kolev I, Nikolova R, Marudova M, et al. Bigel formulations of nanoencapsulated St. John’s wort extract—an approach for enhanced wound healing. Gels. 2023;9(5):360. doi: 10.3390/gels9050360. 72. Elkhateeb OM, Badawy MEI, Noreldin AE, Abou-Ahmed HM, El-Kammar MH, Elkhenany HA. Comparative evaluation of propolis nanostructured lipid carriers and its crude extract for antioxidants, antimicrobial activity, and skin regeneration potential. BMC Complement Med Ther. 2022;22(1):256. doi: 10.1186/s12906-022-03737-4. 73. Ghaffari S, Alihosseini F, Rezayat Sorkhabadi SM, Arbabi Bidgoli S, Mousavi SE, Haghighat S, et al. Nanotechnology in wound healing; semisolid dosage forms containing curcumin-ampicillin solid lipid nanoparticles, in-vitro, ex-vivo and in-vivo characteristics. Adv Pharm Bull. 2018;8(3):395-400. doi: 10.15171/apb.2018.046. 74. Veintramuthusankar U. Development of mupirocin-tinidazole solid-lipid nanoparticles loaded topical gel for the management of bacterial wound infections. Res J Sci Technol. 2020;12(1):57-64. doi: 10.5958/2349-2988.2020.00007.8. 75. Singh A, Iqubal MK, Mittal S, Qizilbash FF, Sartaz A, Kumar S, et al. Designing and evaluation of dermal targeted combinatorial nanostructured lipid carrier gel loaded with curcumin and resveratrol for accelerating cutaneous wound healing. Part Sci Technol. 2023. doi:10.1080/02726351.2023.2205348. 76. Lee HJ, Jeong M, Na YG, Kim SJ, Lee HK, Cho CW. An EGF- and curcumin-co-encapsulated nanostructured lipid carrier accelerates chronic-wound healing in diabetic rats. Molecules. 2020;25(20):4610. doi: 10.3390/molecules25204610. 77. Carbone C, Caddeo C, Grimaudo MA, Manno DE, Serra A, Musumeci T. Ferulic acid-NLC with lavandula essential oil: a possible strategy for wound-healing? Nanomaterials. 2020;10(5):898. doi: 10.3390/nano10050898
