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Curcumin nanoparticles inhibit corneal neovascularization

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Abstract

Corneal neovascularization is a leading cause for compromised vision. Therapeutic prevention of corneal neovascularization is a major clinical challenge, and there is a compelling need to seek effective and safe therapy for this pathology. This study is aimed to evaluate curcumin nanoparticle for prevention of corneal neovascularization. MePEG-PCL nanoparticles were successfully prepared and characterized. The nanoparticle of curcumin has shown increased efficiency in preventing angiogenic sprouting in vitro. Topical delivery of curcumin nanoparticle in the eye showed enhanced retention of curcumin in the cornea, and significant improvement in prevention of corneal neovascularization over free curcumin as graded clinically and by histopathology; suppression in the expression of VEGF, inflammatory cytokines, and MMP was evidenced in the treated cornea. Curcumin inhibited NFκB in LPS-induced corneal cells. Histopathology and scanning electron microscopy showed absence of any adverse change in the corneal structure following application of curcumin nanoparticle. Therefore, we conclude that curcumin nanoparticle can be a potential candidate for prevention of corneal neovascularization.

Key message

  • Curcumin nanoparticles show enhanced retention of curcumin in the cornea.

  • Curcumin NPs suppress the expression of VEGF, inflammatory cytokines, and MMP.

  • Curcumin NPs prevent corneal neovascularization by suppressing the NFκB pathway.

  • Curcumin NPs may be a promising candidate for prevention of corneal neovascularization.

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References

  1. Ambati BK, Nozaki M, Singh N, Takeda A, Jani PD, Suthar T, Albuquerque RJ, Richter E, Sakurai E, Newcomb MT et al (2006) Corneal avascularity is due to soluble VEGF receptor-1. Nature 443:993–997

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Cursiefen C, Chen L, Saint-Geniez M, Hamrah P, Jin Y, Rashid S, Pytowski B, Persaud K, Wu Y, Streilein JW et al (2006) Proc Natl Acad Sci U S A 103:11405–11410

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Amano S, Rohan R, Kuroki M, Tolentino M, Adamis AP (1998) Requirement for vascular endothelial growth factor in wound- and inflammation-related corneal neovascularization. Invest Ophthalmol Vis Sci 39:18–22

    CAS  PubMed  Google Scholar 

  4. Cursiefen C, Chen L, Borges LP, Jackson D, Cao J, Radziejewski C, D’Amore PA, Dana MR, Wiegand SJ, Streilein JW (2004) VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J Clin Invest 113:1040–1050

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Gong Y, Koh DR (2010) Neutrophils promote inflammatory angiogenesis via release of preformed VEGF in an in vivo corneal model. Cell Tissue Res 339:437–448

    Article  PubMed  Google Scholar 

  6. Philipp W, Speicher L, Humpel C (2000) Expression of vascular endothelial growth factor and its receptors in inflamed and vascularized human corneas. Invest Ophthalmol Vis Sci 41:2514–2522

    CAS  PubMed  Google Scholar 

  7. Gan L, Fagerholm P, Palmblad J (2004) Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in the regulation of corneal neovascularization and wound healing. Acta Ophthalmol Scand 82:557–563

    Article  CAS  PubMed  Google Scholar 

  8. Benelli U, Ross JR, Nardi M, Klintworth GK (1997) Corneal neovascularization induced by xenografts or chemical cautery: inhibition by cyclosporin A. Invest Ophthalmol Vis Sci 38:274–282

    CAS  PubMed  Google Scholar 

  9. Hayashi A, Popovich KS, Kim HC, de Juan E (1997) Role of protein tyrosine phosphorylation in rat corneal neovascularization. Graefes Arch Clin Exp Ophthalmol 235:460–467

    Article  CAS  PubMed  Google Scholar 

  10. Lee P, Wang CC, Adamis AP (1998) Ocular neovascularization: an epidemiologic review. Surv Ophthalmol 43:245–269

    Article  CAS  PubMed  Google Scholar 

  11. Gonzalez L, Loza RJ, Han KY, Sunoqrot S, Cunningham C, Purta P, Drake J, Jain S, Hong S, Chang JH (2013) Nanotechnology in corneal neovascularization therapy—a review. J Ocul Pharmacol Ther 29:124–134

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Sarchahi AA, Maimandi A, Tafti AK, Amani M (2008) Effects of acetylcysteine and dexamethasone on experimental corneal wounds in rabbits. Ophthalmic Res 40:41–48

    Article  CAS  PubMed  Google Scholar 

  13. Guidera AC, Luchs JI, Udell IJ (2001) Keratitis, ulceration, and perforation associated with topical nonsteroidal anti-inflammatory drugs. Ophthalmology 108:936–944

    Article  CAS  PubMed  Google Scholar 

  14. Shakiba Y, Mansouri K, Rezaei N, Arshadi D (2009) Corneal neovascularization: molecular events and therapeutic options. Recent Patents Inflamm Allergy Drug Discov 3:221–231

    Article  CAS  Google Scholar 

  15. Koenig Y, Bock F, Kruse FE, Stock K, Cursiefen C (2012) Angioregressive pretreatment of mature corneal blood vessels before keratoplasty: fine-needle vessel coagulation combined with anti-VEGFs. Cornea 31:887–892

    Article  PubMed  Google Scholar 

  16. Kim SW, Ha BJ, Kim EK, Tchah H, Kim TI (2008) The effect of topical bevacizumab on corneal neovascularization. Ophthalmology 115:33–38

    Article  Google Scholar 

  17. Oh JY, Kim MK, Wee WR (2009) Subconjunctival and intracorneal bevacizumab injection for corneal neovascularization in lipid keratopathy. Cornea 28:1070–1073

    Article  PubMed  Google Scholar 

  18. Ambati BK, Anand A, Joussen AM, Kuziel WA, Adamis AP, Ambati J (2003) Sustained inhibition of corneal neovascularization by genetic ablation of CCR5. Invest Ophthalmol Vis Sci 44:590–593

    Article  PubMed  Google Scholar 

  19. Ambati BK, Joussen AM, Anand A, Adamis AP, Ambati J (2003) Inhibition of corneal neovascularization by genetic ablation of CCR2. Cornea 22:465–467

    Article  PubMed  Google Scholar 

  20. Lu P, Li L, Liu G, van Rooijen N, Mukaida N, Zhang X (2009) Opposite roles of CCR2 and CX3CR1 macrophages in alkali-induced corneal neovascularization. Cornea 28:562–569

    Article  CAS  PubMed  Google Scholar 

  21. Lan W, Petznick A, Heryati S, Rifada M, Tong L (2012) Nuclear factor-kB: central regulator in ocular surface inflammation and diseases. Ocul Surf 10:137–148

    Article  PubMed  Google Scholar 

  22. Zhao F, Gong Y, Hu Y, Lu M, Wang J, Dong J, Chen D, Chen L, Fu F, Qiu F (2015) Curcumin and its major metabolites inhibit the inflammatory response induced by lipopolysaccharide: translocation of nuclear factor-κB as potential target. Mol Med Rep 11:3087–3093

    CAS  PubMed  Google Scholar 

  23. Gaudana R, Jwala J, Boddu SH (2009) Recent perspectives in ocular drug delivery. Pharm Res 26:1197–1216

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Chang JH, Gabison EE, Kato T (2001) Corneal neovascularization. Curr Opin Ophthalmol 12:242–249

    Article  CAS  PubMed  Google Scholar 

  25. Rawas-Qalaji M, Williams CA (2012) Advances in ocular drug delivery. Curr Eye Res 37:345–356

    Article  CAS  PubMed  Google Scholar 

  26. Guha R, Chowdhury S, Palui H, Mishra A, Basak S, Mandal TK, Hazra S, Konar A (2013) Doxorubicin-loaded MePEG-PCL nanoparticles for prevention of posterior capsular opacification. Nanomedicine (Lond) 8:1415–1428

    Article  CAS  Google Scholar 

  27. Qazi Y, Stagg B, Singh N, Singh S, Zhang X, Luo L, Simonis J, Kompella UB, Ambati BK (2012) Nanoparticle-mediated delivery of shRNA. VEGF-A plasmids regresses corneal neovascularization. Invest Ophthalmol Vis Sci 53:2837–2844

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Al-Abd AM, Kim NH, Song SC, Lee SJ, Kuh HJ (2009) A simple HPLC method for doxorubicin in plasma and tissues of nude mice. Arch Pharm Res 32:605–611

    Article  CAS  PubMed  Google Scholar 

  29. Bian F, Zhang MC, Zhu Y (2008) Inhibitory effect of curcumin on corneal neovascularization in vitro and in vivo. Ophthalmologica 222:178–186

    Article  CAS  PubMed  Google Scholar 

  30. Klein R, Lobes LA Jr (1976) Ocular alkali burns in a large urban area. Ann Ophthalmol 8:1185–1189

    CAS  PubMed  Google Scholar 

  31. Morgan SJ (1987) Chemical burns of the eye: causes and management. Br J Ophthalmol 71:854

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Huang FC, Chan WK, Moriarty KJ (1998) Novel cytokine release inhibitors. Part I: triterpenes. Bioorg Med Chem Lett 8:1883–1886

    Article  CAS  PubMed  Google Scholar 

  33. Kim JS, Choi JS, Chung SK (2010) The effect of curcumin on corneal neovascularization in rabbit eyes. Curr Eye Res 35:274–280

    Article  CAS  PubMed  Google Scholar 

  34. Sivak JM, Ostriker AC, Woolfenden A, Demirs J, Cepeda R, Long D, Anderson K, Jaffee B (2011) Pharmacologic uncoupling of angiogenesis and inflammation during initiation of pathological corneal neovascularization. J Biol Chem 286:44965–44975

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Ma DH, Chen JK, Kim WS, Hao YX, Wu HC, Tsai RJ, Hwang DG, Zhang F (2001) Expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinase 1 and 2 in inflammation-induced corneal neovascularisation. Ophthalmic Res 33:353–362

    Article  CAS  PubMed  Google Scholar 

  36. Arbiser JL, Klauber N, Rohan R, van Leeuwen R, Huang MT, Fisher C, Flynn E, Byers HR (1998) Curcumin is an in vivo inhibitor of angiogenesis. Mol Med 4:376–383

    PubMed Central  CAS  PubMed  Google Scholar 

  37. Gao C, Ding Z, Liang B, Chen N, Cheng D (2003) Study on the effects of curcumin on angiogenesis. Zhong Yao Cai 26:499–502

    PubMed  Google Scholar 

  38. Gupta SK, Kumar B, Nag TC (2011) Curcumin prevents experimental diabetic retinopathy in rats through its hypoglycemic, antioxidant, and anti-inflammatory mechanisms. J Ocul Pharmacol Ther 27:123–130

    Article  CAS  PubMed  Google Scholar 

  39. Anand P, Kunnumakkara AB, New-man RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4:807–818

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We acknowledge the Department of Biotechnology (Grant No. BT/PR13434/NNT/28/469/2009), Government of India, for funding and West Bengal University of Animal & Fishery Sciences and CSIR-IICB for the support.

Conflict of interest

The authors declare no conflict of interests related to this study.

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    Authors and Affiliations

    1. West Bengal University of Animal and Fishery Sciences, 37 & 68 Kshudiram Bose Sarani, Belgachia, Kolkata, 700037, West Bengal, India

      Nirparaj Pradhan & Sarbani Hazra

    2. CSIR-Indian Institute of Chemical Biology, 4, Raja SC Mullick Road, Kolkata, 700032, West Bengal, India

      Rajdeep Guha, Sushovan Chowdhury, Sudip Nandi & Aditya Konar

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    1. Nirparaj Pradhan
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    2. Rajdeep Guha
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    3. Sushovan Chowdhury
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    Correspondence to Aditya Konar or Sarbani Hazra.

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    Nirparaj Pradhan and Rajdeep Guha contributed equally to this work.

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    Pradhan, N., Guha, R., Chowdhury, S. et al. Curcumin nanoparticles inhibit corneal neovascularization. J Mol Med 93, 1095–1106 (2015). https://doi.org/10.1007/s00109-015-1277-z

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    • DOI: https://doi.org/10.1007/s00109-015-1277-z

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