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Therapeutic applications and delivery systems for triptolide

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Abstract

Triptolide (TPL) is a natural compound and active component of Tripterygium wilfordii Hook F., an Asian native woody vine widely used for over 200 years in Chinese medicine. Hot water, ethanol–ethyl acetate, and chloroform–methanol extracts are the first reported TPL preparations in the literature, and since then, several studies for application in inflammation processes and cancer are described due to the antitumor, anti-inflammatory, and immunosuppressive characteristics of the molecule. However, physicochemical properties such as poor solubility and bioavailability are the main concerns regarding the TPL safety and efficacy in clinical studies since trials have reported adverse side effects alongside the excellent TPL therapeutic effects. Here, we review the main TPL applications and issues related to the drug usage, and a comprehensive summary of diseases is provided. Special emphasis is given to drug delivery systems designed to overcome the TPL physicochemical characteristics such as poor drug solubility, and how to increase efficacy and obtain a safe drug profile.

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References

  1. Bonifácio BV, da Silva PB. Aparecido dos Santos Ramos M, et al. Nanotechnology-based drug delivery systems and herbal medicines: a review. Int J Nanomed. 2013;9:1–15.

    Article  CAS  Google Scholar 

  2. Tao X, Cai JJ, Lipsky PE. The identity of immunosuppressive components of the ethyl acetate extract and chloroform methanol extract (T2) of Tripterygium wilfordii Hook F. J Pharmacol Exp Ther. 1995;272:1305–12.

    CAS  PubMed  Google Scholar 

  3. Chen SR, Dai Y, Zhao J, et al. A mechanistic overview of triptolide and celastrol, natural products from Tripterygium wilfordii Hook F. Front Pharmacol. 2018;9:1–13.

    Article  CAS  Google Scholar 

  4. Tao X, Lipsky PE. The Chinese anti-inflammatory and immunosuppressive herbal remedy Tripterygium wilfordii Hook F. Rheum Dis Clin N Am. 2000;26(1):29–50. https://doi.org/10.1016/s0889-857X(05)70118-6

  5. Wang L, Zhang L, Hou Q, et al. Triptolide attenuates proteinuria and podocyte apoptosis via inhibition of NF-κB/GADD45B. Sci Rep. 2018;8:1–11.

    Google Scholar 

  6. Brinker AM, Ma J, Lipsky PE, Raskin I. Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae). Phytochemistry. 2007;68:732–66.

    Article  CAS  PubMed  Google Scholar 

  7. Peng MG, Shu ZC, Tao FJ, et al. Aggregate cell suspension cultures of Tripterygium wilfordii Hook. F. for triptolide, wilforgine, and wilforine production. Plant Cell Tissue Organ Cult. 2013;112:109–16.

    Article  CAS  Google Scholar 

  8. Chen G, Hao B, Ju D, Liu M, Zhao H, du Z, et al. Pharmacokinetic and pharmacodynamic study of triptolide-loaded liposome hydrogel patch under microneedles on rats with collagen-induced arthritis. Acta Pharm Sin B. 2015;5:569–76.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Mujumdar N, MacKenzie TN, Dudeja V, et al. Triptolide induces cell death in pancreatic cancer cells by apoptotic and autophagic pathways. Gastroenterology. 2010;139:598–608.

    Article  CAS  PubMed  Google Scholar 

  10. Hou W, Liu B, Xu H. Triptolide: medicinal chemistry, chemical biology and clinical progress. Eur J Med Chem. 2019;176:378–92.

    Article  CAS  PubMed  Google Scholar 

  11. Chen JG, Liu YF, Gao TW. Preparation and anti-inflammatory activity of triptolide ethosomes in an erythema model. J Liposome Res. 2010;20:297–303.

    Article  PubMed  CAS  Google Scholar 

  12. Chen G, Hao B, Ju D, Liu M, Zhao H, du Z, et al. Pharmacokinetic and pharmacodynamic study of triptolide-loaded liposome hydrogel patch under microneedles on rats with collagen-induced arthritis. Acta Pharm Sin B. 2015;5:569–76.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Chen J-G, Jiang Y, Yang Z-B. Preparation of triptolide ethosomes. African J Pharm Pharmacol. 2012;6:1341–7.

    Google Scholar 

  14. Mei Z, Wu Q, Hu S, Lib X, Yang X. Triptolide loaded solid lipid nanoparticle hydrogel for topical application. Drug Dev Ind Pharm. 2005;31:161–8.

    Article  CAS  PubMed  Google Scholar 

  15. Mei Z, Chen H, Weng T, et al. Solid lipid nanoparticle and microemulsion for topical delivery of triptolide. Eur J Pharm Biopharm. 2003;56:189–96.

    Article  CAS  PubMed  Google Scholar 

  16. Wu B, Lu ST, Zhang LJ, Zhuo RX, Xu HB, Huang SW. Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment. Int J Nanomedicine. 2017;12:1853–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kesarwani K, Gupta R. Bioavailability enhancers of herbal origin: an overview. Asian Pac J Trop Biomed. 2013;3:253–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. He MF, Huang YH, Wu LW, Ge W, Shaw PC, But PPH. Triptolide functions as a potent angiogenesis inhibitor. Int J Cancer. 2010;126:266–78.

    Article  CAS  PubMed  Google Scholar 

  19. Tao X, Lipsky PE. The Chinese anti-inflammatory and immunosuppressive herbal remedy Tripterygium wilfordii Hook F. Rheum Dis Clin N Am. 2000;26:29–50.

    Article  CAS  Google Scholar 

  20. Zhou Z-L, Yang Y-X, Ding J, Li YC, Miao ZH. Triptolide: structural modifications, structure–activity relationships, bioactivities, clinical development and mechanisms. Nat Prod Rep. 2012;29:457–75.

    Article  CAS  PubMed  Google Scholar 

  21. Qu F, Wu CS, Hou JF, Jin Y, Zhang JL. Sphingolipids as new biomarkers for assessment of delayed-type hypersensitivity and response to Triptolide. PLoS One. 2012;7:e52454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Manzo SG, Zhou ZL, Wang YQ, Marinello J, He JX, Li YC, et al. Natural product triptolide mediates cancer cell death by triggering CDK7-dependent degradation of RNA polymerase II. Cancer Res. 2012;72:5363–73.

    Article  CAS  PubMed  Google Scholar 

  23. Tu L, Su P, Zhang Z, et al. Genome of Tripterygium wilfordii and identification of cytochrome P450 involved in triptolide biosynthesis. Nat Commun. 2020;11:1–12.

    Article  CAS  Google Scholar 

  24. Tao X, Cush J, Garret M, et al. A phase I study of ethyl acetate extract of the Chinese antirheumatic herb Tripterygium wilfordii Hook F in rheumatoid arthristis. J Rheumatol. 2001;28:2160–7.

    CAS  PubMed  Google Scholar 

  25. Tao X, Younger J, Fan FZ, Wang B, Lipsky PE. Benefit of an extract of Tripterygium wilfordii Hook F in patients with rheumatoid arthritis: a double-blind, placebo-controlled study. Arthritis Rheum. 2002;46:1735–43.

    Article  PubMed  Google Scholar 

  26. Han R, Rostami-Yazdi M, Gerdes S, Mrowietz U. Triptolide in the treatment of psoriasis and other immune-mediated inflammatory diseases. Br J Clin Pharmacol. 2012;74:424–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zheng G, Wang Z, Li C, et al. Triptolide regulates immune response network against systemic lupus erythematosus. Proc - 2016 IEEE Int Conf Bioinforma Biomed BIBM 2016. 2017:1409–14.

  28. Qui D, Kao PN. Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the Chinese medicinal herb Tripterygium wilfordii Hook. F. Drugs R D. 2003;4:1–18.

    Article  Google Scholar 

  29. Wu S, Guo N. Clinical observation on effect of triptolide tablet in treating patients with psoriasis vulgaris. Chin J Integr Med. 2005;11:147–8.

    Article  PubMed  Google Scholar 

  30. Lu Y, Zhang Y, Li L, Feng X, Ding S, Zheng W, et al. TAB1: a target of triptolide in macrophages. Chem Biol. 2014;21:246–56.

    Article  CAS  PubMed  Google Scholar 

  31. Ziaei S, Halaby R. Immunosuppressive, anti-inflammatory and anti-cancer properties of triptolide: a mini review. Avicenna J phytomedicine. 2016;6:149–64.

    CAS  Google Scholar 

  32. Cai Y-Y, Lin W-P, Li A-P, Xu JY. Combined effects of curcumin and triptolide on an ovarian cancer cell line. Asian Pacific J Cancer Prev. 2013;14:4267–71.

    Article  Google Scholar 

  33. Sun L, Zhang S, Jiang Z, Huang X, Wang T, Huang X, et al. Triptolide inhibits COX-2 expression by regulating mRNA stability in TNF-α-treated A549 cells. Biochem Biophys Res Commun. 2011;416:99–105.

    Article  CAS  PubMed  Google Scholar 

  34. Yang S, Chen J, Guo Z, Xu XM, Wang L, Pei XF, et al. Triptolide inhibits the growth and metastasis of solid tumors. Mol Cancer Ther. 2003;2:65–72.

    CAS  PubMed  Google Scholar 

  35. Reno TA, Kim JY, Raz DJ. Triptolide inhibits lung cancer cell migration, invasion, and metastasis. Ann Thorac Surg. 2015;100:1817–25.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Messina ME, Halaby R. Does triptolide induce lysosomal-mediated apoptosis in human breast cancer cells? Med Hypotheses. 2011;77:91–3.

    Article  CAS  PubMed  Google Scholar 

  37. Phillips PA, Dudeja V, McCarroll JA, et al. Triptolide induces pancreatic cancer cell death via inhibition of heat shock protein 70. Cancer Res. 2007;67:9407–16.

    Article  CAS  PubMed  Google Scholar 

  38. Kim ST, Kim SY, Lee J, et al. Triptolide as a novel agent in pancreatic cancer: the validation using patient derived pancreatic tumor cell line. BMC Cancer. 2018;18:1–7.

    Article  Google Scholar 

  39. Liu B, Zhang H, Li J, Lu C, Chen G, Zhang G, et al. Triptolide downregulates treg cells and the level of IL-10, TGF-β, and VEGF in melanoma-bearing mice. Planta Med. 2013;79:1401–7.

    Article  CAS  PubMed  Google Scholar 

  40. Wang C, Shan Y, Yang J, Xu X, Zhuang B, Fan Y, et al. Inhibition of cancer angiogenesis using triptolide nanoparticles. J Biomed Nanotechnol. 2015;11:805–15.

    Article  CAS  PubMed  Google Scholar 

  41. Chen M, Wang JM, Wang D, et al. Triptolide inhibits migration and proliferation of fibroblasts from ileocolonic anastomosis of patients with Crohn’s disease via regulating the miR-16-1/HSP70 pathway. Mol Med Rep. 2019;19:4841–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhou H, Guo W, Long C, Wang H, Wang J, Sun X. Triptolide inhibits proliferation of Epstein-Barr virus-positive B lymphocytes by down-regulating expression of a viral protein LMP1. Biochem Biophys Res Commun. 2015;456:815–20.

    Article  CAS  PubMed  Google Scholar 

  43. Leuenroth SJ, Okuhara D, Shotwell JD, Markowitz GS, Yu Z, Somlo S, et al. Triptolide is a traditional Chinese medicine-derived inhibitor of polycystic kidney disease. Proc Natl Acad Sci U S A. 2007;104:4389–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Cheng S, LeBlanc KJ, Li L. Triptolide preserves cognitive function and reduces neuropathology in a mouse model of Alzheimer’s disease. PLoS One. 2014;9:e108845.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Chen JG, Liu YF, Gao TW. Preparation and anti-inflammatory activity of triptolide ethosomes in an erythema model. J Liposome Res. 2010;20:297–303.

    Article  PubMed  CAS  Google Scholar 

  46. Zhang Y-G, Sheng Q-S, Wang H-K, Lv L, Zhang J, Chen JM, et al. Triptolide improves nerve regeneration and functional recovery following crush injury to rat sciatic nerve. Neurosci Lett. 2014;561:198–202.

    Article  CAS  PubMed  Google Scholar 

  47. Greb JE, Goldminz AM, Elder JT, Lebwohl MG, Gladman DD, Wu JJ, et al. Psoriasis. Nat Rev Dis Prim. 2016;2:16082.

    Article  PubMed  Google Scholar 

  48. Cline A, Hill D, Lewallen R, Feldman SR. Current status and future prospects for biologic treatments of psoriasis. Expert Rev Clin Immunol. 2016;12:1273–87.

    Article  CAS  PubMed  Google Scholar 

  49. Zhao J, Di T, Wang Y, et al. Multi-glycoside of Tripterygium wilfordii Hook. F. ameliorates imiquimod-induced skin lesions through a STAT3-dependent mechanism involving the inhibition of Th17-mediated inflammatory responses. Int J Mol Med. 2016;38:747–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. He L, Liang Z, Zhao F, et al. Modulation of IL-37 expression by triptolide and triptonide in THP-1 cells. Cell Mol Immunol. 2015;1292:515–8.

    Article  CAS  Google Scholar 

  51. Fotiadou C, Lazaridou E, Sotiriou E, Ioannides D. Targeting IL-23 in psoriasis: current perspectives. Psoriasis Targets Ther. 2018;8:1–5.

    Article  CAS  Google Scholar 

  52. Chen N, Sun J, Song Y, et al. Tripterygium wilfordii polyglycoside reduces the proliferation and inflammatory cytokines secretion of Hacat cells by regulating the balance of neutrophil elastase and trappin-2. 2016;9:12219–27.

  53. Koo J, Desai R. Traditional Chinese medicine in dermatology. Dermatol Ther. 2003;16:98–105.

    Article  PubMed  Google Scholar 

  54. Wu S, Guo N. Clinical observation on effect of triptolide tablet in treating patients with psoriasis vulgaris. Chin J Integr Med. 2005;11:147–8.

    Article  PubMed  Google Scholar 

  55. Jin H-Z, Li F, He C-X, et al. Efficacy and safety of Tripterygium wilfordii Hook F versus acitretin in moderate to severe psoriasis vulgaris: a randomized clinical trial. Chin Med J (Engl). 2015;128:443.

    Article  CAS  Google Scholar 

  56. Li-min L, Wen-jing J, Xing-xia Z, et al. Regulation on function and maturation of plasmocytoid dendritic cells by triptolide. Chinese J Microbiol Immunol. 2011;31:6–9.

    Google Scholar 

  57. Wang G, Wang C, Xu X, Jia H. Two cases of bullous systemic lupus erythematosus treated successfully with T2 and low-dose corticosteroids. Dermatologica Sin. 2016;34:92–5.

    Article  Google Scholar 

  58. Lazarov A, Mor A, Cordoba M, Mekori YA. Rheumatoid neutrophilic dermatitis: an initial dermatological manifestation of seronegative rheumatoid arthritis. J Eur Acad Dermatology Venereol. 2002;16:74–6.

    Article  CAS  Google Scholar 

  59. Zhang K, Zhou G, Yu C, et al. Pustular rheumatoid neutrophilic dermatitis with Koebner phenomenon. Indian J Dermatol Venereol Leprol. 2012;82:569–71.

    Google Scholar 

  60. Boyd AS. Neldner Kenneth H. The isomorphic response of Koebner. Int J Dermatol. 1990;29:401–10.

    Article  CAS  PubMed  Google Scholar 

  61. Jiang Q, Tang X-P, Chen X-C, Xiao H, Liu P, Jiao J. Will Chinese external therapy with compound Tripterygium wilfordii Hook F gel safely control disease activity in patients with rheumatoid arthritis: design of a double-blinded randomized controlled trial. BMC Complement Altern Med. 2017;17:444.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Cibere J, Deng Z, Lin Y, Runmei O, He Y, Wang Z, et al. A randomized double blind, placebo controlled trial of topical Tripterygium wilfordii in rheumatoid arthritis: reanalysis using logistic regression analysis. J Rheumatol. 2003;30:465–7.

    PubMed  Google Scholar 

  63. Meng H, Zhu L, Ni W, You LS, Jin J, Qian WB. Triptolide inhibits the proliferation of cells from lymphocytic leukemic cell lines in association with downregulation of NF-κB activity and miR-16-1*. Acta Pharmacol Sin. 2011;32:503–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Noel P, Von Hoff DD, Saluja AK, et al. Triptolide and its derivatives as cancer therapies. Trends Pharmacol Sci. 2019;40:327–41.

    Article  CAS  PubMed  Google Scholar 

  65. Ziaei S, Halaby R. Immunosuppressive, anti-inflammatory and anti-cancer properties of triptolide: a mini review. Avicenna J phytomedicine. 2016;6:149–64.

    CAS  Google Scholar 

  66. Chueh F, Chen Y, Hsu S, et al. Triptolide induced DNA damage in A375.S2 human malignant melanoma cells is mediated via reduction of DNA repair genes. Oncol Rep. 2013;29:613–8.

    Article  CAS  PubMed  Google Scholar 

  67. Tang X, Zhu Y, Tao W, Wei B, Lin XL. Synergistic effect of triptolide combined with 5-fluorouracil on colon carcinoma. Postgr Med J. 2007;83:338–43.

    Article  CAS  Google Scholar 

  68. Huang X, Yang M, Jin J. Triptolide enhances the sensitivity of multiple myeloma cells to dexamethasone via microRNAs. Leuk Lymphoma. 2012;53:1188–95.

    Article  CAS  PubMed  Google Scholar 

  69. Qiao Z, He M, He M, et al. Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells. Oncol Lett. 2016;11:3527–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Feng J, Xu M, Wang J, Zhou S, Liu Y, Liu S, et al. Biomaterials sequential delivery of nanoformulated α-mangostin and triptolide overcomes permeation obstacles and improves therapeutic e ff ects in pancreatic cancer. Biomaterials. 2020;241:119907.

    Article  CAS  PubMed  Google Scholar 

  71. Cai Y-Y, Lin W-P, Li A-P, Xu JY. Combined effects of curcumin and triptolide on an ovarian cancer cell line. Asian Pacific J Cancer Prev. 2013;14:4267–71.

    Article  Google Scholar 

  72. Liu Y, Xiao E, Yuan L, Li G. Triptolide synergistically enhances antitumor activity of oxaliplatin in colon carcinoma in vitro and in vivo. DNA Cell Biol. 2014;33:418–25.

    Article  CAS  PubMed  Google Scholar 

  73. Wischke C, Eckart R, Lendlein A. Dermal drug delivery by nanocarriers. J Control Release. 2016;242:1–2.

    Article  CAS  PubMed  Google Scholar 

  74. Tang Y, Wang J, Cheng J, Wang L. Antiestrogenic activity of triptolide in human breast cancer cells MCF-7 and immature female mouse. Drug Dev Res. 2017;78:164–9.

    Article  CAS  PubMed  Google Scholar 

  75. Hu H, Huang G, Wang H, Li X, Wang X, Feng Y, et al. Inhibition effect of triptolide on human epithelial ovarian cancer via adjusting cellular immunity and angiogenesis. Oncol Rep. 2018;39:1191–6.

    CAS  PubMed  Google Scholar 

  76. Jiang W, Chen M, Xiao C, Yang W, Qin Q, Tan Q, et al. Triptolide suppresses growth of breast cancer by targeting HMGB1 in vitro and in vivo. Biol Pharm Bull. 2019;42:892–9.

    Article  CAS  PubMed  Google Scholar 

  77. Antonoff MB, Chugh R, Skube SJ, Dudeja V, Borja-Cacho D, Clawson KA, et al. Role of Hsp-70 in triptolide-mediated cell death of neuroblastoma. J Surg Res. 2010;163:72–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Ma J, Sun Y, Yu Y, et al. Triptolide enhances the sensitivity of pancreatic cancer PANC-1 cells to gemcitabine by inhibiting TLR4/NF-κB signaling. 2019;11:3750–60.

  79. Wang H, Ma D, Wang C, Zhao S, Liu C. Triptolide inhibits invasion and tumorigenesis of hepatocellular carcinoma MHCC-97H cells through NF-κB signaling. Med Sci Monit. 2016;22:1827–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Sun L, Zhang S, Jiang Z, Huang X, Wang T, Huang X, et al. Triptolide inhibits COX-2 expression by regulating mRNA stability in TNF-α-treated A549 cells. Biochem Biophys Res Commun. 2011;416:99–105.

    Article  CAS  PubMed  Google Scholar 

  81. Hang S, Wang X, Li H. Triptolide inhibits viability and migration while promotes apoptosis in nephroblastoma cells by regulation of miR-193b-3p. Exp Mol Pathol. 2019;108:80–8.

    Article  CAS  PubMed  Google Scholar 

  82. Zhang L, Yu JS. Triptolide reverses helper T cell inhibition and down-regulates IFN-γ induced PD-L1 expression in glioma cell lines. J Neuro-Oncol. 2019;143:429–36.

    Article  CAS  Google Scholar 

  83. Wang J, Zhang Z, Li R, Sun W, Chen J, Zhang H, et al. Triptolide inhibits pituitary adenoma cell viability, migration and invasion via ADAM12/EGFR signaling pathway. Life Sci. 2018;194:150–6.

    Article  CAS  PubMed  Google Scholar 

  84. Chahibi Y. Molecular communication for drug delivery systems: a survey. Nano Commun Netw. 2017;11:90–102.

    Article  Google Scholar 

  85. Xi C, Peng S, Wu Z, Zhou Q, Zhou J. Toxicity of triptolide and the molecular mechanisms involved. Biomed Pharmacother. 2017;90:531–41.

    Article  CAS  PubMed  Google Scholar 

  86. Reinholz J, Landfester K, Mailänder V. The challenges of oral drug delivery via nanocarriers. Drug Deliv. 2018;25:1694–705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Nakamura Y, Mochida A, Choyke PL, Kobayashi H. Nanodrug delivery: is the enhanced permeability and retention effect sufficient for curing cancer? Bioconjug Chem. 2016;27:2225–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Vicentini FTMDC, Borgheti-Cardoso LN, Depieri LV, et al. Delivery systems and local administration routes for therapeutic siRNA. Pharm Res. 2013:915–31.

  89. Mota AH, Rijo P, Molpeceres J, Reis CP. Broad overview of engineering of functional nanosystems for skin delivery. Int J Pharm. 2017;532:710–28.

    Article  CAS  PubMed  Google Scholar 

  90. Iqbal B, Ali J, Baboota S. Recent advances and development in epidermal and dermal drug deposition enhancement technology. Int J Dermatol. 2018;57:646–60.

    Article  PubMed  Google Scholar 

  91. Rosa J, Suzuki I, Kravicz M, Caron A, Pupo AV, Praça FG, et al. Current non-viral siRNA delivery systems as a promising treatment of skin diseases. Curr Pharm Des. 2018;24:2644–63.

    Article  CAS  PubMed  Google Scholar 

  92. Baroli B. Penetration of nanoparticles and nanomaterials in the skin: fiction or reality? J Pharm Sci. 2010;99:21–50.

    Article  CAS  PubMed  Google Scholar 

  93. Prausnitz MR, Mitragotri S, Langer R. Current status and future potential of transdermal drug delivery. Nat Rev Drug Discov. 2004;3:115–24.

    Article  CAS  PubMed  Google Scholar 

  94. Praca FSG, Garci MWS, Petrilli R, Bentley MVLB. Liquid crystal nanodispersions enable the cutaneous delivery of photosensitizer for topical PDT: fluorescence microscopy study of skin penetration. Curr Nanosci. 2012;8:535–40.

    Article  CAS  Google Scholar 

  95. Rossetti FC, Depieri LV, Praça FG, del Ciampo JO, Fantini MCA, Pierre MBR, et al. Optimization of protoporphyrin IX skin delivery for topical photodynamic therapy: nanodispersions of liquid-crystalline phase as nanocarriers. Eur J Pharm Sci. 2016;83:99–108.

    Article  CAS  PubMed  Google Scholar 

  96. Praça FG, Petrilli R, de Oliveira EJ, et al. Liquid-crystalline nanodispersions containing monoolein for photodynamic therapy of skin diseases: a mini-review. Curr Nanosci. 2017;13:1–8.

    Article  CAS  Google Scholar 

  97. Tiossi RFJ, Da Costa JC, Miranda MA, et al. In vitro and in vivo evaluation of the delivery of topical formulations containing glycoalkaloids of Solanum lycocarpum fruits. Eur J Pharm Biopharm. 2014;88:28–33.

    Article  CAS  PubMed  Google Scholar 

  98. Benson HAE, Grice JE, Mohammed Y, Namjoshi S, Roberts MS. Topical and transdermal drug delivery: from simple potions to smart technologies. Curr Drug Deliv. 2019;16:444–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Schneider M, Stracke F, Hansen S, Schaefer UF. Nanoparticles and their interactions with the dermal barrier. Dermatoendocrinol. 2009;1:197–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Rehman K, Zulfakar MH. Recent advances in gel technologies for topical and transdermal drug delivery. Drug Dev Ind Pharm. 2014;40:433–40.

    Article  CAS  PubMed  Google Scholar 

  101. Li XJ, Jiang ZZ, Zhang LY. Triptolide: Progress on research in pharmacodynamics and toxicology. J Ethnopharmacol. 2014;155:67–79.

    Article  CAS  PubMed  Google Scholar 

  102. Xie L, Zhao Y, Duan J, et al. Integrated proteomics and metabolomics reveal the mechanism of nephrotoxicity induced by triptolide. Chem Res Toxicol. 2020:1–10.

  103. You-lan C, Ju-rong Y, Da-jie L. Some toxicities of triptolide in mice and dogs. Acta Pharmacol Sin. 1981;2:70–2.

    Google Scholar 

  104. Georg IG, Patil SP, Saluja AK, et al. Triptolide prodrugs. United States Patents. 2018;US 2018 /0.

  105. Liu J, He Q, Pomper MG, et al. Glucose conjugates of triptolide, analogs and uses thereof. United States Patents. 2019.

  106. Xu H, Liu B. Triptolide-targeted delivery methods. Eur J Med Chem. 2019;164:342–51.

    Article  CAS  PubMed  Google Scholar 

  107. Wischke C, Ruhl E, Lendlein A. Dermal drug delivery by nanocarriers. J Control Release. 2016;242:1–2.

    Article  CAS  PubMed  Google Scholar 

  108. Pan J. RNA polymerase—an important molecular target of triptolide in cancer cells. Cancer Lett. 2010;292:149–52.

    Article  CAS  PubMed  Google Scholar 

  109. Yu D, Liu Y, Zhou Y, et al. Triptolide suppresses IDH1-mutated malignancy via Nrf2-driven glutathione metabolism. Proc Natl Acad Sci. 2020;117:1–9.

    Article  Google Scholar 

  110. Lu H, Wang J, Wang T, et al. Recent progress on nanostructures for drug delivery applications. J Nanomater. 2016;2016:1–12.

    Google Scholar 

  111. Ru D, Ding C, Liu L, Liu H, Shen M, Duan Y, et al. PH sensitive triptolide-loaded liposome calcium phosphate nanoparticles exhibit enhanced anti-tumor activities against ovarian cancer without damaging the reproductive system. J Biomed Nanotechnol. 2017;13:1413–24.

    Article  CAS  PubMed  Google Scholar 

  112. Messina ME, Halaby R. Does triptolide induce lysosomal-mediated apoptosis in human breast cancer cells? Med Hypotheses. 2011;77:91–3.

    Article  CAS  PubMed  Google Scholar 

  113. Cai X Jun, Fei W dong, Xu Y ying, et al. combination of metronomic administration and target delivery strategies to improve the anti-angiogenic and anti-tumor effects of triptolide. Drug Deliv Transl Res 2019;10:93–107.

  114. Xue M, Zhao Y, Li XJ, Jiang ZZ, Zhang L, Liu SH, et al. Comparison of toxicokinetic and tissue distribution of triptolide-loaded solid lipid nanoparticles vs free triptolide in rats. Eur J Pharm Sci. 2012;47:713–7.

    Article  CAS  PubMed  Google Scholar 

  115. Gu Y, Tang X, Yang M, Yang D, Liu J. Transdermal drug delivery of triptolide-loaded nanostructured lipid carriers: preparation, pharmacokinetic, and evaluation for rheumatoid arthritis. Int J Pharm. 2019;554:235–44.

    Article  CAS  PubMed  Google Scholar 

  116. Aliberti ALM, de Queiroz AC, Praça FSG, Eloy JO, Bentley MVLB, Medina WSG. Ketoprofen microemulsion for improved skin delivery and in vivo anti-inflammatory effect. AAPS PharmSciTech. 2017;18:2783–91.

    Article  CAS  PubMed  Google Scholar 

  117. Rossetti FC, Lopes LB, Carollo ARH, Thomazini JA, Tedesco AC, Bentley MVLB. A delivery system to avoid self-aggregation and to improve in vitro and in vivo skin delivery of a phthalocyanine derivative used in the photodynamic therapy. J Control Release. 2011;155:400–8.

    Article  CAS  PubMed  Google Scholar 

  118. Lopes LB. Overcoming the cutaneous barrier with microemulsions. Pharmaceutics. 2014;6:52–77.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. Chen H, Chang X, Weng T, Zhao X, Gao Z, Yang Y, et al. A study of microemulsion systems for transdermal delivery of triptolide. J Control Release. 2004;98:427–36.

    Article  CAS  PubMed  Google Scholar 

  120. Chen H, Mou D, Du D, et al. Hydrogel-thickened microemulsion for topical administration of drug molecule at an extremely low concentration. Int J Pharm. 2007;341:78–84.

    Article  CAS  PubMed  Google Scholar 

  121. Chen L, Zhao X, Cai J, Guan Y, Wang S, Liu H, et al. Triptolide-loaded microemulsion-based hydrogels: physical properties and percutaneous permeability. Acta Pharm Sin B. 2013;3:185–92.

    Article  Google Scholar 

  122. Xu L, Pan J, Chen Q, Yu Q, Chen H, Xu H, et al. In vivo evaluation of the safety of triptolide-loaded hydrogel-thickened microemulsion. Food Chem Toxicol. 2008;46:3792–9.

    Article  CAS  PubMed  Google Scholar 

  123. Li X, Mao Y, Li K, Shi T, Yao H, Yao J, et al. Pharmacokinetics and tissue distribution study in mice of triptolide-loaded lipid emulsion and accumulation effect on pancreas. Drug Deliv. 2016;23:1344–54.

    Article  CAS  PubMed  Google Scholar 

  124. Zhang L, Wang T, Li Q, Huang J, Xu H, Li J, et al. Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo. Int J Nanomedicine. 2016;11:2663–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Liu H, Shen M, Zhao D, et al. The effect of triptolide-loaded exosomes on the proliferation and apoptosis of human ovarian cancer SKOV3 cells. Biomed Res Int. 2019;2019.

  126. Liu J, Cheng H, Han L, Qiang Z, Zhang X, Gao W, et al. Synergistic combination therapy of lung cancer using paclitaxel- and triptolide-coloaded lipid–polymer hybrid nanoparticles. Drug Des Devel Ther. 2018;12:3199–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Shan QQ, Jiang XJ, Wang FY, Shu ZX, Gui SY. Cubic and hexagonal liquid crystals as drug carriers for the transdermal delivery of triptolide. Drug Deliv. 2019;26:490–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

National Institute of Science and Technology of Pharmaceutical Nanotechnology (INCT), which is supported FAPESP, Brazil, grant #2014/50928-2, and CNPQ, Brazil, grant #465687/2014-8. J.S.R.V., PhD FAPESP fellowship #2019/04448-2.

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  1. School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil

    Juliana Santos Rosa Viegas, Fabíola Garcia Praça, Marcelo Kravicz & Maria Vitoria Lopes Badra Bentley

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  1. Juliana Santos Rosa Viegas
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  2. Fabíola Garcia Praça
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  3. Marcelo Kravicz
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  4. Maria Vitoria Lopes Badra Bentley
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Correspondence to Maria Vitoria Lopes Badra Bentley.

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Viegas, J.S., Praça, F.G., Kravicz, M. et al. Therapeutic applications and delivery systems for triptolide. Drug Deliv. and Transl. Res. 10, 1584–1600 (2020). https://doi.org/10.1007/s13346-020-00827-z

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