Surface Modification of Nanoparticles for Ocular Drug Delivery

  • Kathleen Halasz
  • Yashwant V PathakEmail author


The eye is a crucial sensory organ and is responsible not only for sight but also for maintaining balance. Ocular diseases are categorized as being either anterior or posterior segment diseases based on the affected segment of the eye. Anterior segment diseases affect the cornea, iris, pupil, ciliary body and/or conjunctiva. Posterior segment diseases affect the sclera, choroid, fovea, optic nerve, retina, and/or vitreous humor. The anterior segment of the eye can be treated via topical administration such as eye drops, while the posterior segment requires either an intravitreal or subconjunctival injection. Surface-modified nanoparticles have made significant headway in the treatment of various diseases. Research has proven that the VEGF pathway may be targeted for treatment in various diseases, such as those affecting the eye. Although receptor-targeted drug delivery shows many advantageous in the treatment of various diseases there are also several challenges that must be overcome, such as proper receptor identification as well as carrier formulation. Additionally, each patient undergoing receptor-targeted treatment must be evaluated to determine target expression, distribution pattern, and the density of receptors on the surface of the same factors undoubtedly prove the potential of nanoparticle surface modifying techniques in the treatment of various ocular diseases.


Angiogenesis Endothelial growth factor receptor(s) Nanoparticle(s) Ligand(s) 



Special thanks to Shannon Kelly, Muhammed Iqbal, and Nikhil Kulkarni.


  1. 1.
    Choi, S.-W., Kim, W.-S., & Kim, J.-H. (2003). Surface modification of functional Nanoparticles for controlled drug Deivery. Journal of Dispersion Science and Technology, 24(3), 475–487.Google Scholar
  2. 2.
    Vhora, I., Patil, S., Bhatt, P., Gandhi, R., Baradia, D., & Misra, A. (2014). Receptor-targeted drug delivery: Current perspective and challenges. Therapeutic Delivery, 5(9), 1007–1024.Google Scholar
  3. 3.
    Kelly, S., Halasz, K., & Sutariya, V. (2017). HIF-1a inhibitors for the treatment of posterior segment ocular diseases. International Journal of Nanomedicine and Nanosurgery, 3(1).Google Scholar
  4. 4.
    Friedman, D., O'Colmain, B., Munoz, B., Tomany, S., McCarty, C., de Jong, P., et al. (2011). Prevalence of age-related macular degeneration in the United States. Archives of Ophthalmology, 129(9), 1188.Google Scholar
  5. 5.
    Hazare, S., Yang, R., Chavan, S., Menon, M., & Chougule, M. (2016). Aging disorders of the eye: Challenges and approaches for their treatment. In Y. Pathak, V. Sutariya, & A. A. Hirani (Eds.), Nano-biomaterials for ophthalmic drug delivery. Switzerland: Springer.Google Scholar
  6. 6.
    Wong, T., & Scott, I. (2010). Retinal-vein occlusion. New England Journal of Medicine, 363, 2135–2144.Google Scholar
  7. 7.
    Riaz, S., Khan, M., Qazi, Z.-u.-D., Qadeer, R., & Shaukat, S. (2017). Different patterns of retinal vein occlusion on Fundus Fluorescein angiography. Ophthalmology, 15(2), 77–81.Google Scholar
  8. 8.
    Zhang, Y., Yang, M., Park, J., Singelyn, J., Ma, H., Sailor, M., et al. (2009). A surface-charge study on cellular-uptake behavior of F3-peptide-conjugated iron oxide nanoparticles. Small, 5(17), 1990–1996.Google Scholar
  9. 9.
    Jo, D., Kim, J., Lee, T., & Kim, J. (2015). Size, surface charge, and shape determine therapeutic effects of nanoparticles on brain and retinal diseases. Nanomedicine, 11(7), 1603–1611.Google Scholar
  10. 10.
    Miura, T., Miyake, N., Tanabe, K., & Yoshinari, M. (2011). Change in zeta potential with physicochemical treatment of surface of Anatase-form Titania particles. Journal of Oral Tissue Engineering, 9(2), 64–70.Google Scholar
  11. 11.
    Clogston, J., & Patri, A. (2011). Zeta Potential Measurement. In S. Mcneil (Ed.), Characterization of Nanoparticles intended for drug delivery. Methods in molecular biology (Vol. 697). New York: Humana Press.Google Scholar
  12. 12.
    Bagwe, R., Hilliard, L., & Tan, W. (2006). Surface modification of silica Nanoparticles to reduce aggregation and nonspecific binding. Langmuir, 22(9), 4357–4362.Google Scholar
  13. 13.
    Amadio, M., Govoni, S., & Pascale, A. (2016). Targeting VEGF in eye neovascularization: What's new? A comprehensive review on current therapies and oligonucleotide-based interventions under development. Pharmacological Research, 103, 253–269.Google Scholar
  14. 14.
    Zhu, R., Wang, Z., Liang, P., He, X., Zhuang, X., Huang, R., et al. (2017). Efficient VEGF targeting delivery of DOX using Bevacizumab conjugated SiO2@LDH for anti-neuroblastoma therapy. Acta Biomaterialia, 63, 163–180.Google Scholar
  15. 15.
    Goel, S., Chen, F., Hong, H., Valdovinos, H., Hernandez, R., Shi, S., et al. (2014). VEGF121-conjugated Mesoporous silica Nanoparticle: A tumor targeted drug delivery system. ACS Applied Materials and Interfaces, 6, 21677–21685.Google Scholar
  16. 16.
    Bhatt, P., Vhora, I., Patil, S., Amrutita, J., Bhattacharya, C., Misra, A., et al. (2016). Role of antibodies in diagnosis and treatment of ovarian cancer: Basic approach and clinical status. Journal of Controlled Release, 226, 148–167.Google Scholar
  17. 17.
    Patel, J., Amrutiya, J., Bhatt, P., Javia, A., Jain, M., & Misra, A. (2018). Targeted delivery of monoclonal antibody ocnjugated docetaxel loaded PLGA nanoparticles into EGFR overexpressed lung tumour cells. Journal of Microencapsulation, 35, 204–217.Google Scholar
  18. 18.
    Shi, Y., Zhou, M., Zhang, J., & Lu, W. (2015). Preparation and cellular targeting study of VEGF-conjugated PLGA nanoparticles. Journal of Microencapsulation, 32(7), 699–704.Google Scholar
  19. 19.
    Nagpal, M., Nagpal, K., & Nagpal, P. (2007). A comparative debate on the various anti-vascular endothelial growth factor drugs: Pegaptanib sodium (Macugen), ranibizumab (Lucentis) and bevacizumab (Avastin). Indian Journal of Ophthalmology, 55(6), 437–439.Google Scholar
  20. 20.
    Pillai, G. (2014). Nanomedicines for Cancer therapy: An update of FDA approved and those under various stages of development. SOJ Pharmacy and Pharmaceutical Sciences, 1(2), 13.Google Scholar
  21. 21.
    Malavade, S. (2016). Challenges in ocular pharmacokinetics and drug delivery. In V. Sutariya, A. Hirani, & Y. Pathak (Eds.), Nano-biomaterials for ophthalmic drug delivery (pp. 593–612). Switzerland: Springer.Google Scholar
  22. 22.
    Kompella, U., Bandi, N., & Ayalasomayajula, S. (2003). Subconjunctival nano- and microparticles sustain retinal delivery of budesonide, a corticosteroid capable of inhibiting VEGF expression. Investigative Ophthalmology and Visual Science, 44(3), 1192–1201.Google Scholar
  23. 23.
    Hirani, A., & Pathak, Y. (2016). Introduction to nanotechnology with special reference to ophthalmic delivery. In V. Sutariya, A. Hirani, & Y. Pathak (Eds.), Nano-biomaterials for ophthalmic drug delivery (pp. 1–8). Switzerland: Springer.Google Scholar
  24. 24.
    Hirani, A., et al. (2014). Triamcinolone acetonide nanoparticles incorporated in thermoreversible gels for age-related macular degeneration. Pharmaceutical Development and Technology, 61–66.Google Scholar
  25. 25.
    Kvanta, A., Algvere, P., Berglin, L., & Seregrad, S. (1996). Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor. Investigative Ophthalmology and Visual Science, 37(9), 1929–1934.Google Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences, College of PharmacyUniversity of South FloridaTampaUSA
  2. 2.College of Pharmacy, University of South FloridaTampaUSA
  3. 3.Adjunct professor at Faculty of PharmacyAirlangga UniversitySurabayaIndonesia

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