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Curcumin-loaded nanofibers for targeting endometriosis in the peritoneum of a mouse model

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Abstract

Endometriosis is a common, chronic gynecological disorder associated with ongoing pelvic pain, infertility, and adhesions in reproductive age women. Current therapeutic strategies are not effective and the recurrent nature of endometriosis makes it difficult to treat. In this study, we have designed a drug delivery system to control sustained and prolonged release of curcumin in the peritoneum and pelvic cavity of a mouse model of endometriosis. Poly ε-Caprolactone (PCL) and poly ethylene glycol (PEG) polymers were used to synthesize curcumin loaded nanofibers. After scanning electron microscopy (SEM) observation of the nanofiber’s morphology, we evaluated the drug release profile and in vitro degradation rate of the curcumin-loaded nanofibers. Next, we tested these nanofibers in vivo in the peritoneum of an endometriosis mouse model to determine their anti-endometriosis effects. Histological evaluations were also performed. Curcumin loaded nanofibers were successfully synthesized in the 8 and 10 wt% polymers. The release test of the curcumin-loaded nanofibers showed that approximately 23% of the loaded curcumin was released during 30 min, 35% at 24 h, and 50% at 30 days. Endometriosis was successfully induced in Balb/c mice, as noted by the observed characteristics of endometriosis in all of the mice and confirmation of endometriosis by hematoxylin and eosin (H&E) staining. In vivo experiments showed the ability of these implanted curcumin loaded nanofibers to mitigate endometriosis. We observed a considerable reduction in the endometrial glands and stroma, along with significant reduction in infiltration of inflammatory cells. Implantable curcumin loaded nanofibers successfully mitigated intraperitoneal endometriosis.

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References

  1. Jana S, Rudra DS, Paul S, Swarnakar S. Curcumin delays endometriosis development by inhibiting MMP-2 activity. Indian J Biochem Biophys. 2012;49:342–8.

  2. Zhang Y, Cao H, Hu YY, Wang H, Zhang CJ. Inhibitory effect of curcumin on angiogenesis in ectopic endometrium of rats with experimental endometriosis. Int J Mol Med. 2011;27:87–94.

  3. Pluchino N, Freschi L,Wenger JM, Streuli I. Innovations in classical hormonal targets for endometriosis. Expert Rev Clin Pharm. 2016;9:317–27.

    Article  CAS  Google Scholar 

  4. Culley L, Law C, Hudson N, Denny E, Mitchell H, Baumgarten M, et al. The social and psychological impact of endometriosis on women’s lives: a critical narrative review. Hum Reprod Update. 2013;19:625–39.

    Article  Google Scholar 

  5. Apostolopoulos NV, Alexandraki KI, Gorry A, Coker A. Association between chronic pelvic pain symptoms and the presence of endometriosis. Arch Gynecol Obstet. 2016;293:439–45.

    Article  Google Scholar 

  6. Khine YM, Taniguchi F, Harada T. Clinical management of endometriosis‐associated infertility. Reprod Med Biol. 2016;15:217–25.

    Article  Google Scholar 

  7. Tulandi T, Chen MF, Took SA, Watkin K. A study of nerve fibers and histopathology of postsurgical, postinfectious, and endometriosis related adhesions. Obstet Gynecol. 1998;92:766–8.

    CAS  Google Scholar 

  8. Baldi A, Campioni M, Signorile PG. Endometriosis: pathogenesis, diagnosis, therapy and association with cancer (review). Oncol Rep. 2008;19:843–6.

    CAS  Google Scholar 

  9. Heidemann LN, Hartwell D, Heidemann CH, Jochumsen KM. The relation between endometriosis and ovarian cancer—a review. Acta Obstet Gynecol Scand. 2014;93:20–31.

    Article  Google Scholar 

  10. Vanhie A, Tomassetti C, Peeraer K, Meuleman C, D'Hooghe T. Challenges in the development of novel therapeutic strategies for treatment of endometriosis. Expert Opin Ther Targets. 2016;20:593–600.

    Article  Google Scholar 

  11. Rice VM. Conventional medical therapies for endometriosis. Ann NY Acad Sci. 2002;955:343–52.

    Article  Google Scholar 

  12. Yildiz C, Kacan T, Akkar OB, Karakus S, Seker M, Kacan SB, et al. Effect of imatinib on growth of experimental endometriosis in rats. Eur J Obstet Gynecol Reprod Biol. 2016;197:159–63.

    Article  CAS  Google Scholar 

  13. Ulrich U, Wilde RL De. New guidelines on diagnosis and treatment of endometriosis in German-speaking countries. Gynecol Minim Invasive Ther. 2016;1:41–3.

    Article  Google Scholar 

  14. Berlanda N, Vercellini P, Fedele L. The outcomes of repeat surgery for recurrent symptomatic endometriosis. Curr Opin Obstet Gynecol. 2010;22:320–5.

    Google Scholar 

  15. Vercellini P, Somigliana E, Vigano P, Matteis SD, Barbara G, Fedele L. The effect of second-line surgery on reproductive performance of women with recurrent endometriosis: a systematic review. Acta Obstet Gynecol Scand. 2009;88:1074–82.

    Article  Google Scholar 

  16. Barkalina N, Charalambous C, Jones C, Coward K. Nanotechnology in reproductive medicine: emerging applications of nanomaterials. Nanomedicine. 2014;10:921–38.

    Article  Google Scholar 

  17. Surendiran A, Sandhiya S, Pradhan SC, Adithan C. Novel applications of nanotechnology in medicine. Indian J Med Res. 2009;130:689–701.

  18. Nikalje AP. Nanotechnology and its applications in medicine. Med Chem. 2015;5:81–9.

    Article  Google Scholar 

  19. Boisseau P, Loubaton B. Nanomedicine, nanotechnology in medicine. Comptes Rendus Phys. 2011;12:620–36.

    Article  CAS  Google Scholar 

  20. Ge Y, Li S, Wang S, Moore R. Nanomedicine: principles and perspectives. 1st ed. New York, NY: Springer-Verlag; 2014.

    Google Scholar 

  21. Boroumand S, Hosseini S, Salehi M, Faridi Majidi R. Drug-loaded electrospun nanofibrous sheets as barriers against postsurgical adhesions in mice model. Nanomed Res J. 2017;2:64–72.

  22. Chen DW, Liu SJ. Nanofibers used for delivery of antimicrobial agents. Nanomed (Lond). 2015;10:1959–71.

    Article  CAS  Google Scholar 

  23. Priyadarsini KI. The chemistry of curcumin: from extraction to therapeutic agent. Molecules. 2014;19:20091–112.

    Article  Google Scholar 

  24. Esatbeyoglu T, Huebbe P, Ernst IMA, Chin D, Wagner AE, Rimbach G. Curcumin—from molecule to biological function. Angew Chem Int Ed Engl. 2012;51:5308–32.

    Article  CAS  Google Scholar 

  25. Julie S, Jurenka M. Anti-inflammatory properties of curcumin, a major constituent. Altern Med Rev. 2009;14:141–53.

    Google Scholar 

  26. Kohli K, Ali Jm Ansari MJ, Raheman Z. Curcumin: a natural antiinflammatory agent. Indian J Pharmacol. 2005;37:141–7.

    Article  CAS  Google Scholar 

  27. Merrell JG, McLaughlin SW, Laurencin CT, Chen AF, Nair LS. Curcumin‐loaded poly (ε‐caprolactone) nanofibres: diabetic wound dressing with anti‐oxidant and anti‐inflammatory properties. Clin Exp Pharmacol Physiol. 2009;36:1149–56.

    Article  CAS  Google Scholar 

  28. Tsekova P, Spasova M, Manolova N, Rashkov I, Markova N, Georgieva A, et al. Еlectrospun сellulose acetate membranes decorated with curcumin-PVP particles: preparation, antibacterial and antitumor activities. J Mater Sci: Mater Med. 2017;29:9.

  29. Arablou T, Kolahdouz-Mohammadi R. Curcumin and endometriosis: review on potential roles and molecular mechanisms. Biomed Pharmacother. 2018;97:91–7.

    Article  CAS  Google Scholar 

  30. Jana S, Paul S, Swarnakar S. Curcumin as anti-endometriotic agent: implication of MMP-3 and intrinsic apoptotic pathway. Biochem Pharmacol. 2012;83:797–804.

    Article  CAS  Google Scholar 

  31. Swarnakar S, Paul S. Curcumin arrests endometriosis by downregulation of matrix metalloproteinase-9 activity. Indian J Biochem Biophys. 2009;46:59–65.

    CAS  Google Scholar 

  32. Zhang Y, Cao H, Yu Z, Peng HY, Zhang CJ. Curcumin inhibits endometriosis endometrial cells by reducing estradiol production. Iran J Reprod Med. 2013;11:415.

  33. Ravikumar R, Mani G, Venkatachalam S, Venkata RY, Lavanya JS, Choi EY. Tetrahydro curcumin loaded PCL-PEG electrospun transdermal nanofiber patch: preparation, characterization, and in vitro diffusion evaluations. J Drug Deliv Sci Technol. 2018;44:342–8.

    Article  CAS  Google Scholar 

  34. Jiang J, Ceylan M, Zheng Y, Yao L, Asmatulu R, Yang SY. Poly-ε-caprolactone electrospun nanofiber mesh as a gene delivery tool. AIMS Bioeng. 2016;3:528–37.

    Article  CAS  Google Scholar 

  35. Mondal D, Griffith M, Venkatraman SS. Polycaprolactone-based biomaterials for tissue engineering and drug delivery: Current scenario and challenges. Int J Polym Mater Polym Biomater. 2016;65:255–65.

    Article  CAS  Google Scholar 

  36. Bui HT, Chung OH, Cruz JD, Park JS. Fabrication and characterization of electrospun curcumin-loaded polycaprolactone-polyethylene glycol nanofibers for enhanced wound healing. Macromol Res. 2014;22:1288–96.

    Article  CAS  Google Scholar 

  37. Quattrone F, Sanchez AM, Pannese M, Hemmerle T, Vigano P, Candiani M, et al. The targeted delivery of interleukin 4 inhibits development of endometriotic lesions in a mouse model. Reprod Sci. 2015;22:1143–52.

    Article  CAS  Google Scholar 

  38. Sun X-Z, Williams GR, Hou X-X, Zhu L-M. Electrospun curcumin-loaded fibers with potential biomedical applications. Carbohydr Polym. 2013;94:147–53.

    Article  CAS  Google Scholar 

  39. Feng R, Song Z, Zhai G. Preparation and in vivo pharmacokinetics of curcumin-loaded PCL-PEG-PCL triblock copolymeric nanoparticles. Int J Nanomed. 2012;7:4089.

    Article  CAS  Google Scholar 

  40. Irani M, Mir Mohamad Sadeghi G, Haririan I. A novel biocompatible drug delivery system of chitosan/temozolomide nanoparticles loaded PCL-PU nanofibers for sustained delivery of temozolomide. Int J Biol Macromol. 2017;97:744–51.

    Article  CAS  Google Scholar 

  41. Hrib J, Sirc J, Hobzova R, Hampejsova Z, Bosakova Z, Munzarova M, et al. Nanofibers for drug delivery—incorporation and release of model molecules, influence of molecular weight and polymer structure. Beilstein J Nanotechnol. 2015;6:1939–45.

  42. Guo G, Fu SZ, Zhou LX, Liang H, Fan M, Luo F, et al. Preparation of curcumin loaded poly (ε-caprolactone)-poly (ethylene glycol)-poly (ε-caprolactone) nanofibers and their in vitro antitumor activity against Glioma 9L cells. Nanoscale. 2011;3:3825–32.

    Article  CAS  Google Scholar 

  43. Fallah M, Bahrami SH, Ranjbar-Mohammadi M. Fabrication and characterization of PCL/gelatin/curcumin nanofibers and their antibacterial properties. J Ind Text. 2016;46:562–77.

    Article  CAS  Google Scholar 

  44. Thangaraju E, Srinivasan NT, Kumar R, Sehgal PK, Rajiv S. Fabrication of electrospun poly l-lactide and curcumin loaded poly l-lactide nanofibers for drug delivery. Fibers Polym. 2012;13:823–30.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This article has been extracted from the thesis written by SB (Grant No. 94-04-87-31010). This research was supported by Tehran University of Medical Sciences and Health Services. The proposal has been approved by the research ethics committee and was found to be in accordance to the ethical principles and the national norms and standards for conducting Medical Research in Iran.

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Correspondence to Reza Faridi-Majidi or Mohammad Salehi.

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Boroumand, S., Hosseini, S., Pashandi, Z. et al. Curcumin-loaded nanofibers for targeting endometriosis in the peritoneum of a mouse model. J Mater Sci: Mater Med 31, 8 (2020). https://doi.org/10.1007/s10856-019-6337-4

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  • DOI: https://doi.org/10.1007/s10856-019-6337-4

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