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Preparation of luteolin loaded nanostructured lipid carrier based gel and effect on psoriasis of mice

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Abstract

This study investigated a nanostructured lipid carrier (NLC)-gel system containing luteolin (LUT), a potential drug delivery system for the treatment of psoriasis. LUT-NLC was prepared by solvent emulsification ultrasonication method. The particle size was 199.9 ± 2.6 nm, with the encapsulation efficiency of 99.81% and drug loading of 4.06%. X-ray diffractometry (XRD), Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were used to characterize the LUT-NLC. The NLC was dispersed in Carbomer 940 to form the NLC based gel. The rheological characteristics of LUT-NLC-gel showed an excellent shear-thinning behavior (non-Newtonian properties) and coincided with the Herschel-Bulkley model. LUT-NLC-gel (78.89 μg/cm2) exhibited better permeation properties and released over 36 hours than LUT gel (32.17 μg/cm2). The dye-labeled LUT-NLC presented intense fluorescence in the epidermis and dermis by the visualization of fluorescence and confocal microscopy, and it could accumulate in the hair follicles. The effect of LUT-NLC-gel on imiquimod-induced psoriasis mice was evaluated by psoriasis area severity index scoring, spleen index assay, histopathology, and inflammatory cytokines. These results confirmed that LUT-NLC-gel with high dose (80 mg/kg/day) remarkably reduced the level of inflammatory and proliferation factors such as TNF-α, IL-6, IL-17, and IL-23 in both skin lesions and blood. LUT-NLC-gel improved the macroscopic features. Therefore, the LUT-NLC-gel had great potential as an effective delivery system for skin diseases.

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References

  1. Wu S, Tian L. A new flavone glucoside together with known ellagitannins and flavones with anti-diabetic and anti-obesity activities from the flowers of pomegranate (Punica granatum). Nat Prod Res. 2019;33(2):252–7. https://doi.org/10.1080/14786419.2018.1446009.

    Article  CAS  PubMed  Google Scholar 

  2. Rodríguez-Calzada T, Qian M, Strid Å, et al. Effect of UV-B radiation on morphology, phenolic compound production, gene expression, and subsequent drought stress responses in chili pepper (Capsicum annuum L.). Plant Physiol Biochem. 2019;134:94–102. https://doi.org/10.1016/j.plaphy.2018.06.025.

    Article  CAS  PubMed  Google Scholar 

  3. Guenné S, Ouattara N, Ouédraogo N, Ciobica A, Hilou A, Kiendrebéogo M. Phytochemistry and neuroprotective effects of Eclipta alba (L.) Hassk. J Complement Integr Med. 2019;17(1):20190026. https://doi.org/10.1515/jcim-2019-0026.

    Article  CAS  Google Scholar 

  4. Conti P, Caraffa A, Gallenga CE, et al. Powerful anti-inflammatory action of luteolin: Potential increase with IL-38. Biofactors. 2021;47(2):165–9. https://doi.org/10.1002/biof.1718.

    Article  CAS  PubMed  Google Scholar 

  5. Ashrafizadeh M, Ahmadi Z, Farkhondeh T, Samarghandian S. Autophagy regulation using luteolin: new insight into its anti-tumor activity. Cancer Cell Int. 2020;20(1):537. https://doi.org/10.1186/s12935-020-01634-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Manzoor MF, Ahmad N, Ahmed Z, et al. Novel extraction techniques and pharmaceutical activities of luteolin and its derivatives. J Food Biochem. 2019;43(9):e12974. https://doi.org/10.1111/jfbc.12974.

    Article  CAS  PubMed  Google Scholar 

  7. Schnarr L, Segatto ML, Olsson O, Zuin VG, Kümmerer K. Flavonoids as biopesticides - Systematic assessment of sources, structures, activities and environmental fate. Sci Total Environ. 2022;824:153781. https://doi.org/10.1016/j.scitotenv.2022.153781.

    Article  CAS  PubMed  Google Scholar 

  8. Singla RK, Kumar R, Khan S, Mohit Kumari K, Garg A. Natural Products: Potential Source of DPP-IV Inhibitors. Curr Protein Pept Sci. 2019;20(12):1218–25. https://doi.org/10.2174/1389203720666190502154129.

    Article  CAS  PubMed  Google Scholar 

  9. Kempuraj D, Thangavel R, Kempuraj DD, et al. Neuroprotective effects of flavone luteolin in neuroinflammation and neurotrauma. Biofactors. 2021;47(2):190–7. https://doi.org/10.1002/biof.1687.

    Article  CAS  PubMed  Google Scholar 

  10. Jiang D, Li D, Wu W. Inhibitory effects and mechanisms of luteolin on proliferation and migration of vascular smooth muscle cells. Nutrients. 2013;5(5):1648–59. https://doi.org/10.3390/nu5051648.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ali F, Siddique YH. Bioavailability and Pharmaco-therapeutic Potential of Luteolin in Overcoming Alzheimer’s Disease. CNS Neurol Disord Drug Targets. 2019;18(5):352–65. https://doi.org/10.2174/1871527318666190319141835.

    Article  CAS  PubMed  Google Scholar 

  12. Lin Y, Shi R, Wang X, Shen HM. Luteolin, a flavonoid with potential for cancer prevention and therapy. Curr Cancer Drug Targets. 2008;8(7):634–46. https://doi.org/10.2174/156800908786241050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Imran M, Rauf A, Abu-Izneid T, et al. Luteolin, a flavonoid, as an anticancer agent: A review. Biomed Pharmacother. 2019;112:108612. https://doi.org/10.1016/j.biopha.2019.108612.

    Article  CAS  PubMed  Google Scholar 

  14. Shakeel F, Haq N, Alshehri S, et al. Solubility, thermodynamic properties and solute-solvent molecular interactions of luteolin in various pure solvents. Journal of Molecular Liquids. 2018;255:43–50. https://doi.org/10.1016/j.molliq.2018.01.155.

    Article  CAS  Google Scholar 

  15. McClements DJ. Advances in nanoparticle and microparticle delivery systems for increasing the dispersibility, stability, and bioactivity of phytochemicals. Biotechnol Adv. 2020;38:107287. https://doi.org/10.1016/j.biotechadv.2018.08.004.

    Article  CAS  PubMed  Google Scholar 

  16. Dobreva M, Stefanov S, Andonova V. Natural Lipids as Structural Components of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Topical Delivery. Curr Pharm Des. 2020;26(36):4524–35. https://doi.org/10.2174/1381612826666200514221649.

    Article  CAS  PubMed  Google Scholar 

  17. D’Souza A, Shegokar R. Nanostructured Lipid Carriers (NLCs) for Drug Delivery: Role of Liquid Lipid (Oil). Curr Drug Deliv. 2021;18(3):249–70. https://doi.org/10.2174/1567201817666200423083807.

    Article  CAS  PubMed  Google Scholar 

  18. Gendrisch F, Esser PR, Schempp CM, Wölfle U. Luteolin as a modulator of skin aging and inflammation. Biofactors. 2021;47(2):170–80. https://doi.org/10.1002/biof.1699.

    Article  CAS  PubMed  Google Scholar 

  19. Qing W, Wang Y, Li H, Ma F, Zhu J, Liu X. Preparation and Characterization of Copolymer Micelles for the Solubilization and In Vitro Release of Luteolin and Luteoloside. AAPS PharmSciTech. 2017;18(6):2095–101. https://doi.org/10.1208/s12249-016-0692-y.

    Article  CAS  PubMed  Google Scholar 

  20. Shimul Islam Md, Moshikur Rahman Md, Minamihata Kosuke, Moniruzzaman Muhammad, Kamiya N, Goto M. Choline oleate based micellar system as a new approach for Luteolin formulation: Antioxidant, antimicrobial, and food preservation properties evaluation. J Mol Liq. 2022;365:120151. https://doi.org/10.1016/j.molliq.2022.120151.

    Article  CAS  Google Scholar 

  21. Gutiérrez RMP, Gómez JT, Urby RB, Soto JGC, Parra HR. Evaluation of Diabetes Effects of Selenium Nanoparticles Synthesized from a Mixture of Luteolin and Diosmin on Streptozotocin-Induced Type 2 Diabetes in Mice. Molecules. 2022;27(17):5642. https://doi.org/10.3390/molecules27175642.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Miyashita A, Ito J, Parida IS, et al. Improving water dispersibility and bioavailability of luteolin using microemulsion system. Sci Rep. 2022;12(1):11949. https://doi.org/10.1038/s41598-022-16220-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Elmowafy M, Shalaby K, Elkomy MH, et al. Development and assessment of phospholipid-based luteolin-loaded lipid nanocapsules for skin delivery. Int J Pharm. 2022;629:122375. https://doi.org/10.1016/j.ijpharm.2022.122375.

    Article  CAS  PubMed  Google Scholar 

  24. Liu Y, Wang L, Zhao Y, et al. Nanostructured lipid carriers versus microemulsions for delivery of the poorly water-soluble drug luteolin. Int J Pharm. 2014;476(1–2):169–77. https://doi.org/10.1016/j.ijpharm.2014.09.052.

    Article  CAS  PubMed  Google Scholar 

  25. 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. https://doi.org/10.1080/17425247.2020.1772750.

    Article  CAS  PubMed  Google Scholar 

  26. Weber S, Zimmer A, Pardeike J. Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) for pulmonary application: a review of the state of the art. Eur J Pharm Biopharm. 2014;86(1):7–22. https://doi.org/10.1016/j.ejpb.2013.08.013.

    Article  CAS  PubMed  Google Scholar 

  27. de Souza ML, Dos Santos WM, de Sousa ALMD, et al. Lipid Nanoparticles as a Skin Wound Healing Drug Delivery System: Discoveries and Advances. Curr Pharm Des. 2020;26(36):4536–50. https://doi.org/10.2174/1381612826666200417144530.

    Article  CAS  PubMed  Google Scholar 

  28. Rehman S, Nabi B, Baboota S, Ali J. Tailoring lipid nanoconstructs for the oral delivery of paliperidone: Formulation, optimization and in vitro evaluation. Chem Phys Lipids. 2021;234:105005. https://doi.org/10.1016/j.chemphyslip.2020.105005.

    Article  CAS  PubMed  Google Scholar 

  29. Shevalkar G, Pai R, Vavia P. Nanostructured Lipid Carrier of Propofol: a Promising Alternative to Marketed Soybean Oil-Based Nanoemulsion. AAPS PharmSciTech. 2019;20(5):201. https://doi.org/10.1208/s12249-019-1408-x.

    Article  CAS  PubMed  Google Scholar 

  30. Zingale E, Rizzo S, Bonaccorso A, et al. Optimization of Lipid Nanoparticles by Response Surface Methodology to Improve the Ocular Delivery of Diosmin: Characterization and In-Vitro Anti-Inflammatory Assessment. Pharmaceutics. 2022;14(9):1961. https://doi.org/10.3390/pharmaceutics14091961.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rajpoot K, Prajapati SK, Malaiya A, Jain R, Jain A. Meropenem-Loaded Nanostructured Lipid Carriers For Skin and Soft Tissue Infection Caused by Staphylococcus aureus: Formulation, Design, and Evaluation. AAPS PharmSciTech. 2022;23(7):241. https://doi.org/10.1208/s12249-022-02381-y.

    Article  CAS  PubMed  Google Scholar 

  32. Hajipour H, Sambrani R, Ghorbani M, Mirzamohammadi Z, Nouri M. Sildenafil citrate-loaded targeted nanostructured lipid carrier enhances receptivity potential of endometrial cells via LIF and VEGF upregulation. Naunyn Schmiedebergs Arch Pharmacol. 2021;394(11):2323–31. https://doi.org/10.1007/s00210-021-02153-8.

    Article  CAS  PubMed  Google Scholar 

  33. Bashyal S, Shin CY, Hyun SM, Jang SW, Lee S. Preparation, Characterization, and In Vivo Pharmacokinetic Evaluation of Polyvinyl Alcohol and Polyvinyl Pyrrolidone Blended Hydrogels for Transdermal Delivery of Donepezil HCl. Pharmaceutics. 2020;12(3):270. https://doi.org/10.3390/pharmaceutics12030270.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Parmar PK, Sharma N, Wasil Kabeer S, Rohit A, Bansal AK. Nanocrystal-based gel of apremilast ameliorates imiquimod-induced psoriasis by suppressing inflammatory responses. Int J Pharm. 2022;622:121873. https://doi.org/10.1016/j.ijpharm.2022.121873.

    Article  CAS  PubMed  Google Scholar 

  35. Sentjurc M, Vrhovnik K, Kristl J. Liposomes as a topical delivery system: the role of size on transport studied by the EPR imaging method. J Control Release. 1999;59(1):87–97. https://doi.org/10.1016/s0168-3659(98)00181-3.

    Article  CAS  PubMed  Google Scholar 

  36. Venturini CG, Bruinsmann FA, Contri RV, et al. Co-encapsulation of imiquimod and copaiba oil in novel nanostructured systems: promising formulations against skin carcinoma. Eur J Pharm Sci. 2015;79:36–43. https://doi.org/10.1016/j.ejps.2015.08.016.

    Article  CAS  PubMed  Google Scholar 

  37. Danaei M, Dehghankhold M, Ataei S, et al. Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics. 2018;10(2):57. https://doi.org/10.3390/pharmaceutics10020057.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ogiso T, Yamaguchi T, Iwaki M, Tanino T, Miyake Y. Effect of positively and negatively charged liposomes on skin permeation of drugs. J Drug Target. 2001;9(1):49–59. https://doi.org/10.3109/10611860108995632.

    Article  CAS  PubMed  Google Scholar 

  39. Niu H, Wang W, Dou Z, et al. Multiscale combined techniques for evaluating emulsion stability: A critical review. Adv Colloid Interface Sci. 2023;311:102813. https://doi.org/10.1016/j.cis.2022.102813.

    Article  CAS  PubMed  Google Scholar 

  40. Tesio AY, Robledo SN. Analytical determinations of luteolin. Biofactors. 2021;47(2):141–64. https://doi.org/10.1002/biof.1720.

    Article  CAS  PubMed  Google Scholar 

  41. Sun F, Li B, Guo Y, et al. Effects of ultrasonic pretreatment of soybean protein isolate on the binding efficiency, structural changes, and bioavailability of a protein-luteolin nanodelivery system. Ultrason Sonochem. 2022;88:106075. https://doi.org/10.1016/j.ultsonch.2022.106075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Souto EB, Wissing SA, Barbosa CM, Müller RH. Evaluation of the physical stability of SLN and NLC before and after incorporation into hydrogel formulations. Eur J Pharm Biopharm. 2004;58(1):83–90. https://doi.org/10.1016/j.ejpb.2004.02.015.

    Article  CAS  PubMed  Google Scholar 

  43. de Moura LD, Ribeiro LNM, de Carvalho FV, et al. Docetaxel and Lidocaine Co-Loaded (NLC-in-Hydrogel) Hybrid System Designed for the Treatment of Melanoma. Pharmaceutics. 2021;13(10):1552. https://doi.org/10.3390/pharmaceutics13101552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. 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. https://doi.org/10.1016/s0169-409x(02)00118-7.

    Article  PubMed  Google Scholar 

  45. Teeranachaideekul V, Boonme P, Souto EB, Müller RH, Junyaprasert VB. Influence of oil content on physicochemical properties and skin distribution of Nile red-loaded NLC. J Control Release. 2008;128(2):134–41. https://doi.org/10.1016/j.jconrel.2008.02.011.

    Article  CAS  PubMed  Google Scholar 

  46. Zhao J, Piao X, Shi X, Si A, Zhang Y, Feng N. Podophyllotoxin-Loaded Nanostructured Lipid Carriers for Skin Targeting: In Vitro and In Vivo Studies. Molecules. 2016;21(11):1549. https://doi.org/10.3390/molecules21111549.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Li B, Huang L, Lv P, et al. The role of Th17 cells in psoriasis. Immunol Res. 2020;68(5):296–309. https://doi.org/10.1007/s12026-020-09149-1.

    Article  CAS  PubMed  Google Scholar 

  48. van der Fits L, Mourits S, Voerman JS, et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol. 2009;182(9):5836–45. https://doi.org/10.4049/jimmunol.0802999.

    Article  CAS  PubMed  Google Scholar 

  49. Jemec GB, Wulf HC. The applicability of clinical scoring systems: SCORAD and PASI in psoriasis and atopic dermatitis. Acta Derm Venereol. 1997;77(5):392–3. https://doi.org/10.2340/0001555577392393.

    Article  CAS  PubMed  Google Scholar 

  50. Kim KE, Houh Y, Park HJ, Cho D. Therapeutic Effects of Erythroid Differentiation Regulator 1 on Imiquimod-Induced Psoriasis-Like Skin Inflammation. Int J Mol Sci. 2016;17(2):244. https://doi.org/10.3390/ijms17020244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Hjuler KF, Gormsen LC, Vendelbo MH, Egeberg A, Nielsen J, Iversen L. Systemic Inflammation and Evidence of a Cardio-splenic Axis in Patients with Psoriasis. Acta Derm Venereol. 2018;98(4):390–5. https://doi.org/10.2340/00015555-2873.

    Article  CAS  PubMed  Google Scholar 

  52. Cheng Y, Liu Y, Tan J, et al. Spleen and thymus metabolomics strategy to explore the immunoregulatory mechanism of total withanolides from the leaves of Datura metel L. on imiquimod-induced psoriatic skin dermatitis in mice. Biomed Chromatogr. 2020;34(9):e4881. https://doi.org/10.1002/bmc.4881.

    Article  CAS  PubMed  Google Scholar 

  53. Kubin ME, Kokkonen N, Palatsi R, et al. Clinical Efficiency of Topical Calcipotriol/Betamethasone Treatment in Psoriasis Relies on Suppression of the Inflammatory TNFα - IL-23 - IL-17 Axis. Acta Derm Venereol. 2017;97(4):449–55. https://doi.org/10.2340/00015555-2579.

    Article  CAS  PubMed  Google Scholar 

  54. Khueangchiangkhwang S, Wu Z, Nagano I, Maekawa Y. Trichinella pseudospiralis-secreted 53 kDa protein ameliorates imiquimod-induced psoriasis by inhibiting the IL-23/IL-17 axis in mice. Biochem Biophys Rep. 2022;33:101415. https://doi.org/10.1016/j.bbrep.2022.101415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

Thanks Dr. Jinghan Li for the suggestion of the experiments.

Funding

This project is funded by Livelihood Plan Project of Department of Science and Technology of Liaoning Province (2021JH2/10300069, 2019-ZD-0845); Department of Education of Liaoning Province (LJKZ0918); and National College Students' innovation and entrepreneurship training program (202210163013).

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Authors and Affiliations

  1. School of Function Food and Wine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China

    Hongjia Xu, Hao Hu, Mengyuan Zhao, Caihong Shi & Xiangrong Zhang

  2. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China

    Xiangrong Zhang

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  1. Hongjia Xu
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Hongjia Xu, Hao Hu and Mengyuan Zhao. Caihong Shi was supervised in the study. The first draft of the manuscript was written by Hongjia Xu and all authors commented on previous versions of the manuscript. Xiangrong Zhang wrote, reviewed and edited the study. All authors read and approved the final manuscript.

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Correspondence to Xiangrong Zhang.

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The study was reviewed and approved by the Institutional Animal Ethical Committee with registration number SYPHU-IACUC-S203-0216-103.

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Author Hongjia Xu, Author Hao Hu, Author Mengyuan Zhao, Caihong Shi and Xiangrong Zhang declare that they have no conflict of interest.

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Xu, H., Hu, H., Zhao, M. et al. Preparation of luteolin loaded nanostructured lipid carrier based gel and effect on psoriasis of mice. Drug Deliv. and Transl. Res. 14, 637–654 (2024). https://doi.org/10.1007/s13346-023-01418-4

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