Skip to main content
SpringerLink
Log in

Ocular Delivery of Peptides and Proteins

  • Chapter
  • First Online:
Book cover Drug Delivery for the Retina and Posterior Segment Disease

Abstract

The delivery of protein and peptide therapeutics through ocular route requires considerable knowledge and understanding about eye’s anatomy and physiology. Although this delivery route has high potency and specificity, it exhibits difficulty in absorption through barriers resulting in lower bioavailability as well as crucial stability issues. Due to the complications associated with the most common injectable route for the peptide and protein delivery, there is a surge for the noninvasive route such as ocular which include intravitreal and periocular route. Newer techniques for delivery of these macromolecules involve targeting transporters or receptors to enhance specificity, while approaches such as nanocarriers, prodrug, mucoadhesion, and permeation enhancers have been employed to attain enhanced bioavailability. This chapter addresses pros and cons of ocular delivery of peptides and proteins, significant features of their chemistry, potential and challenges associated with their local and systemic delivery, as well as different ways to attain better protein bioavailability and stability.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Dahiya S, Pathak K. Physicochemical characterization and dissolution enhancement of aceclofenac-hydroxypropyl beta-cyclodextrin binary systems. PDA J Pharm Sci Technol. 2006;60(6):378–88.

    CAS  PubMed  Google Scholar 

  2. Tripathi M, Radhika PR, Sivakumar T. Formulation and evaluation of glipizide hollow microballoons for floating drug delivery. Bull Pharm Res. 2011;1(1):67–74.

    Google Scholar 

  3. Pathak D, Dahiya S, Pathak K. Solid dispersion of meloxicam: factorially designed dosage form for geriatric population. Acta Pharma. 2008;58(1):99–110.

    Article  CAS  Google Scholar 

  4. Dahiya S, Tyagi L. Preparation and evaluation of oxytetracycline hydrochloride microbeads for delayed release. Pak J Pharm Sci. 2008;21(2):103–8.

    CAS  PubMed  Google Scholar 

  5. Verma S, Kumar V, Jyoti, Mishra DN. Formulation, evaluation and optimization of mucoadhesive microspheres of acyclovir. Bull Pharm Res. 2014;4(1):14–20.

    Google Scholar 

  6. Dahiya S, Pathak K, Sharma R. Development of extended release coevaporates and coprecipitates of promethazine HCl with acrylic polymers: formulation considerations. Chem Pharm Bull (Tokyo). 2008;56(4):504–8.

    Article  CAS  Google Scholar 

  7. Dahiya S, Pathak K. Influence of amorphous cyclodextrin derivatives on aceclofenac release from directly compressible tablets. Pharmazie. 2007;62(4):278–83.

    CAS  PubMed  Google Scholar 

  8. Dahiya S, Gupta ON. Formulation and in vitro evaluation of metoprolol tartrate microspheres. Bull Pharm Res. 2011;1(1):31–9.

    Google Scholar 

  9. Patel A, Patel M, Yang X, Mitra AK. Recent advances in protein and peptide drug delivery: a special emphasis on polymeric nanoparticles. Protein Pept Lett. 2014;21(11):1102–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Das S, Bhaumik A. Protein & peptide drug delivery: a fundamental novel approach and future perspective. World J Pharm Pharmaceut Sci. 2016;5(9):763–76.

    CAS  Google Scholar 

  11. Vyas SP, Paliwal R, Paliwal SR. Ocular delivery of peptides and proteins. In: Van Der Walle CF, editor. Peptide and protein delivery. London: Academic Press, Elsevier; 2011. p. 87–103.

    Chapter  Google Scholar 

  12. Gharge V, Pawar P. Recent trends in chitosan based nanotechnology: a reference to ocular drug delivery system. Int J Ophthal Visual Sci. 2017;2(4):98–105.

    Google Scholar 

  13. Srinivasan R, Jain SK. Insulin delivery through the ocular route. Drug Deliv. 1998;5(1):53–5.

    Article  CAS  PubMed  Google Scholar 

  14. Xuan B, McClellan DA, Moore R, Chiou GC. Alternative delivery of insulin via eye drops. Diabetes Technol Ther. 2005;7(5):695–8.

    Article  CAS  PubMed  Google Scholar 

  15. Lee Y-C, Simamora P, Pinsuwan S, Yalkowsky SH. Review on the systemic delivery of insulin via the ocular route. Int J Pharm. 2002;233(1–2):1–18.

    Article  CAS  PubMed  Google Scholar 

  16. Loftsson T, Sigurdsson HH, Konrádsdóttir F, Gísladóttir S, Jansook P, Stefánsson E. Topical drug delivery to the posterior segment of the eye: anatomical and physiological considerations. Pharmazie. 2008;63(3):171–9.

    CAS  PubMed  Google Scholar 

  17. Thrimawithana TR, Young S, Bunt CR, Green C, Alany RG. Drug delivery to the posterior segment of the eye. Drug Discov Today. 2011;16(5–6):270–7.

    Article  CAS  PubMed  Google Scholar 

  18. Joseph RR, Venkatraman SS. Drug delivery to the eye: what benefits do nanocarriers offer? Nanomedicine (Lond). 2017;12(6):683–702.

    Article  CAS  Google Scholar 

  19. Raghava S, Hammond M, Kompella UB. Periocular routes for retinal drug delivery. Expert Opin Drug Deliv. 2004;1(1):99–114.

    Article  PubMed  Google Scholar 

  20. Addo RT. Ocular drug delivery: advances, challenges and applications. Switzerland: Springer; 2016. p. 1–74.

    Book  Google Scholar 

  21. Bruno BJ, Miller GD, Lim CS. Basics and recent advances in peptide and protein drug delivery. Ther Deliv. 2013;4(11):1443–67.

    Article  CAS  PubMed  Google Scholar 

  22. Muheem A, Shakeel F, Jahangir MA, Anwar M, Mallick N, Jain GK, Warsi MH, Ahmad FJ. A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives. Saudi Pharm J. 2016;24(4):413–28.

    Article  PubMed  Google Scholar 

  23. Jitendra SPK, Bansal S, Banik A. Noninvasive routes of proteins and peptides drug delivery. Indian J Pharm Sci. 2011;73(4):367–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Wearley LL. Recent progress in protein and peptide delivery by noninvasive routes. Crit Rev Ther Drug Carrier Syst. 1991;8(4):331–94.

    CAS  PubMed  Google Scholar 

  25. Anand BS, Dey S, Mitra AK. Current prodrug strategies via membrane transporters/receptors. Expert Opin Biol Ther. 2002;2(6):607–20.

    Article  CAS  PubMed  Google Scholar 

  26. Hamalainen KM, Kananen K, Auriola S, Kontturi K, Urtti A. Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera. Invest Ophthal Visual Sci. 1997;38(3):627–34.

    CAS  Google Scholar 

  27. Muralidhar P, Babajan S, Bhargav E, Sowmya C. An overview: protein and peptide based drug delivery. Int J Pharm Sci Rev Res. 2017;2(1):169–78.

    Google Scholar 

  28. Ratnaparkhi MP, Chaudhari SP, Pandya VA. Peptides and proteins in pharmaceuticals. Int J Curr Pharm Res. 2011;3(2):1–9.

    CAS  Google Scholar 

  29. Gill MK. Biopharmaceuticals. New York: Britannica Education Publishing; 2016.

    Google Scholar 

  30. Wrone-Smith T, Nickoloff BJ. Cyclosporin A. In: Burg G, Dummer RG, editors. Strategies for immunointerventions in dermatology. Berlin, Heidelberg: Springer; 1997.

    Google Scholar 

  31. Janeway CA Jr, Travers P, Walport M. Immunobiology: the immune system in health and disease. 5th ed. New York: Garland Science; 2001.

    Google Scholar 

  32. Makowski GS. Advances in clinical chemistry, vol. 56. London: Academic Press (Elsevier); 2012.

    Google Scholar 

  33. Henning RJ, Sawmiller DR. Vasoactive intestinal peptide: cardiovascular effects. Cardiovasc Res. 2001;49(1):27–37.

    Article  CAS  PubMed  Google Scholar 

  34. Delgado M, Pozo D, Ganea D. The significance of vasoactive intestinal peptide in immunomodulation. Pharmacol Rev. 2004;56(2):249–90.

    Article  CAS  PubMed  Google Scholar 

  35. Dahiya R, Singh S, Sharma A, Chennupati SV, Maharaj S. First total synthesis and biological screening of a proline-rich cyclopeptide from a Caribbean marine sponge. Mar Drugs. 2016;14(12):228.

    Article  CAS  PubMed Central  Google Scholar 

  36. Dahiya R, Gautam H. Total synthesis and antimicrobial activity of a natural cycloheptapeptide of marine origin. Mar Drugs. 2010;8(8):2384–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Dahiya R, Gautam H. Synthesis, characterization and biological evaluation of cyclomontanin D. Afr J Pharm Pharmacol. 2011;5(3):447–53.

    Article  CAS  Google Scholar 

  38. Lax R. The future of peptide development in the pharmaceutical industry. PharManufacturing Int Pept Rev. 2010:10–5.

    Google Scholar 

  39. Kumar S, Dahiya R, Khokra SL, Mourya R, Chennupati SV, Maharaj S. Total synthesis and pharmacological investigation of cordyheptapeptide A. Molecules. 2017;22(6):682.

    Article  CAS  PubMed Central  Google Scholar 

  40. Dahiya R, Kumar A, Gupta R. Synthesis, cytotoxic and antimicrobial screening of a proline-rich cyclopolypeptide. Chem Pharm Bull (Tokyo). 2009;57(2):214–7.

    Article  CAS  Google Scholar 

  41. Dahiya R. Total synthesis and biological potential of psammosilenin A. Arch Pharm (Weinheim). 2008;341(8):502–9.

    Article  CAS  Google Scholar 

  42. Dahiya R, Kumar A. Synthetic and biological studies on a cyclopolypeptide of plant origin. J Zhejiang Univ Sci B. 2008;9(5):391–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Dahiya R. Synthesis of a phenylalanine-rich peptide as potential anthelmintic and cytotoxic agent. Acta Pol Pharm. 2007;64(6):509–16.

    PubMed  Google Scholar 

  44. Dahiya R. Synthetic and pharmacological studies on longicalycinin A. Pak J Pharm Sci. 2007;20(4):317–23.

    CAS  PubMed  Google Scholar 

  45. Giltrap AM, Haeckl FPJ, Kurita KL, Linington RG, Payne RJ. Total synthesis of skyllamycins A-C. Chemistry. 2017;23(60):15046–9.

    Article  CAS  PubMed  Google Scholar 

  46. Gu W, Silverman RB. Solid-phase total synthesis of scytalidamide A. J Org Chem. 2003;68(23):8774–9.

    Article  CAS  PubMed  Google Scholar 

  47. Bourel-Bonnet L, Rao KV, Hamann MT, Ganesan A. Solid-phase total synthesis of kahalalide A and related analogues. J Med Chem. 2005;48(5):1330–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Shah ZA, Jabeen A, Soomro S, Mesaik MA, Choudhary MI, Shaheen F. Solid-phase total synthesis of cyclic peptide brachystemin A and its immunomodulating activity. Turk J Chem. 2015;39:930–8.

    Article  CAS  Google Scholar 

  49. Dahiya R, Kaur K. Synthetic and biological studies on natural cyclic heptapeptide: segetalin E. Arch Pharm Res. 2007;30(11):1380–6.

    Article  CAS  PubMed  Google Scholar 

  50. Dahiya R, Kaur K. Synthesis and pharmacological investigation of segetalin C as a novel antifungal and cytotoxic agent. Arzneimittelforschung. 2008;58(1):29–34.

    CAS  PubMed  Google Scholar 

  51. Dahiya R, Gautam H. Solution phase synthesis and bioevaluation of cordyheptapeptide B. Bull Pharm Res. 2011;1(1):1–10.

    Google Scholar 

  52. Dahiya R, Pathak D, Himaja M, Bhatt S. First total synthesis and biological screening of hymenamide E. Acta Pharma. 2006;56(4):399–415.

    CAS  Google Scholar 

  53. Dahiya R. Synthesis, characterization and biological evaluation of a glycine-rich peptide – cherimolacyclopeptide E. J Chil Chem Soc. 2007;52(3):1224–9.

    Article  CAS  Google Scholar 

  54. Dahiya R. Synthesis, spectroscopic and biological investigation of cyclic octapeptide: cherimolacyclopeptide G. Turk J Chem. 2008;32(2):205–15.

    CAS  Google Scholar 

  55. Dahiya R. Synthetic studies on a cyclic hexapeptide from Dianthus superbus. Chem Pap. 2008;62(5):527–35.

    Article  CAS  Google Scholar 

  56. Dahiya R. Synthesis and in vitro cytotoxic activity of a natural peptide of plant origin. J Iran Chem Soc. 2008;5(3):445–52.

    Article  CAS  Google Scholar 

  57. Dahiya R, Maheshwari M, Kumar A. Toward the synthesis and biological evaluation of hirsutide. Monatsh Chem. 2009;140(1):121–7.

    Article  CAS  Google Scholar 

  58. Dahiya R, Gautam H. Synthesis and pharmacological studies on a cyclooligopeptide from marine bacteria. Chin J Chem. 2011;29(9):1911–6.

    Article  Google Scholar 

  59. Dahiya R, Singh S. First total synthesis and biological potential of a heptacyclopeptide of plant origin. Chin J Chem. 2016;34(11):1158–64.

    Article  CAS  Google Scholar 

  60. Dahiya R, Singh S. Synthesis, characterization, and biological activity studies on fanlizhicyclopeptide A. Iran J Pharm Res. 2017;16(3):1178–86.

    Google Scholar 

  61. Dahiya R, Singh S, Kaur K, Kaur R. Total synthesis of a natural cyclooligopeptide from fruits of sugar-apples. Bull Pharm Res. 2017;7(3):151.

    Google Scholar 

  62. Marcucci E, Tulla-Puche J, Albericio F. Solid-phase synthesis of NMe-IB-01212, a highly N-methylated cyclic peptide. Org Lett. 2012;14(2):612–5.

    Article  CAS  PubMed  Google Scholar 

  63. Dahiya R, Singh S. Synthesis, characterization and biological screening of diandrine A. Acta Pol Pharm. 2017;74(3):873–80.

    PubMed  Google Scholar 

  64. Dahiya R, Singh S. Toward the synthesis and pharmacological screening of a natural cycloheptapeptide of plant origin. Nat Prod Commun. 2017;12(3):379–83.

    PubMed  Google Scholar 

  65. Nielsen DS, Hoang HN, Lohman RJ, Diness F, Fairlie DP. Total synthesis, structure, and oral absorption of a thiazole cyclic peptide, sanguinamide A. Org Lett. 2012;14(22):5720–3.

    Article  CAS  PubMed  Google Scholar 

  66. Wu X, Stockdill JL, Wang P, Danishefsky SJ. Total synthesis of cyclosporine: access to N-methylated peptides via isonitrile coupling reactions. J Am Chem Soc. 2010;132(12):4098–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Thompson C, Ge M, Kahne D. Synthesis of vancomycin from the aglycon. J Am Chem Soc. 1999;121(6):1237–44.

    Article  CAS  Google Scholar 

  68. Bodanszky M, Klausner YS, Lin CY, Mutt V, Said SI. Synthesis of the vasoactive intestinal peptide (VIP). J Am Chem Soc. 1974;96(15):4973–8.

    Article  CAS  PubMed  Google Scholar 

  69. Halban PA. Structural domains and molecular life styles of insulin and its precursors in the pancreatic beta cell. Diabetologia. 1991;34:767–78.

    Article  CAS  PubMed  Google Scholar 

  70. Dey S, Mitra AK. Transporters and receptors in ocular drug delivery: opportunities and challenges. Exp Opin Drug Deliv. 2005;2:201–4.

    Article  CAS  Google Scholar 

  71. Sadeghi AM, Dorkoosh FA, Avadi MR, Saadat P, Rafiee-Tehrani M, Junginger HE. Preparation, characterization and antibacterial activities of chitosan, N-trimethyl chitosan (TMC) and N-diethylmethyl chitosan (DEMC) nanoparticles loaded with insulin using both ionotropic gelation and polyelectrolyte complexation methods. Int J Pharm. 2008;355(1–2):299–306.

    Article  CAS  PubMed  Google Scholar 

  72. Dragan S, Cristea M, Luca C, Simionescu BC. Polyelectrolyte complexes. 1. Synthesis and characterisation of some insoluble polyanionepolycation complexes. J Polym Sci Polym Chem. 1996;34(17):3485–94.

    Article  CAS  Google Scholar 

  73. Grotta JC. Current medical and surgical therapy for cerebrovascular disease. N Engl J Med. 1987;317(24):1505–16.

    Article  CAS  PubMed  Google Scholar 

  74. Barot M, Bagui M, Gokulgandhi MR, Mitra AK. Prodrug strategies in ocular drug delivery. Med Chem. 2012;8(4):753–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Järvinen T, Niemi R. Prodrug approaches to ophthalmic drug delivery. In: Stella VJ, Borchardt RT, Hageman MJ, Oliyai R, Maag H, Tilley JW, editors. Prodrugs. Biotechnology: pharmaceutical aspects, vol. V. New York: Springer; 2007. p. 126–46.

    Google Scholar 

  76. Gaudana R, Ananthula HK, Parenky A, Mitra AK. Ocular drug delivery. AAPS J. 2010;12(3):348–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Mathiowitz E, Chickering DE III, Lehr C-M. Bioadhesive drug delivery systems: fundamentals, novel approaches and development, vol. 98. NewYork: Marcel Dekker Inc.; 1999. p. 343.

    Book  Google Scholar 

  78. Khobragade PK, Puranik PK. Chitosan: a mucoadhesive polymer. World J Pharm Pharmaceut Sci. 2015;4(04):1829–47.

    CAS  Google Scholar 

  79. Pescina S, Sonvico F, Santi P, Nicoli S. Therapeutics and carriers: the dual role of proteins in nanoparticles for ocular delivery. Curr Top Med Chem. 2015;15(4):369–85.

    Article  CAS  PubMed  Google Scholar 

  80. De Campos AM, Sánchez A, Alonso MJ. Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to cyclosporin A. Int J Pharm. 2001;224(1–2):159–68.

    Article  PubMed  Google Scholar 

  81. Alonso MJ, Sánchez A. The potential of chitosan in ocular drug delivery. J Pharm Pharmacol. 2003;55(11):1451–63.

    Article  CAS  PubMed  Google Scholar 

  82. Pleyer U, Elkins B, Rückert D, Lutz S, Grammer J, Chou J, Schmidt KH, Mondino BJ. Ocular absorption of cyclosporine A from liposomes incorporated into collagen shields. Curr Eye Res. 1994;13(3):177–81.

    Article  CAS  PubMed  Google Scholar 

  83. Gokce EH, Sandri G, Bonferoni MC, Rossi S, Ferrari F, Güneri T, Caramella C. Cyclosporine A loaded SLNs: evaluation of cellular uptake and corneal cytotoxicity. Int J Pharm. 2008;364(1):76–86.

    Article  CAS  PubMed  Google Scholar 

  84. Gökçe EH, Sandri G, Eğrilmez S, Bonferoni MC, Güneri T, Caramella C. Cyclosporinea-loaded solid lipid nanoparticles: ocular tolerance and in vivo drug release in rabbit eyes. Curr Eye Res. 2009;34(11):996–1003.

    Article  PubMed  CAS  Google Scholar 

  85. Prokai L, Prokai-Tatrai K. Peptide transport and delivery into the central nervous system. Basel: Birkha¨user-Verlag; 2003.

    Book  Google Scholar 

  86. Lajavardi L, Camelo S, Agnely F, Luo W, Goldenberg B, Naud MC, Behar-Cohen F, de Kozak Y, Bochot A. New formulation of vasoactive intestinal peptide using liposomes in hyaluronic acid gel for uveitis. J Control Release. 2009;139(1):22–30.

    Article  CAS  PubMed  Google Scholar 

  87. Kaur IP, Batra A. Chapter 25. Ocular penetration enhancers. In: Touitou E, Barry BW, editors. Enhancement in drug delivery. Boca Raton: Taylor and Francis Group, CRC Press; 2006.

    Google Scholar 

  88. Newton C, Gebhardt BM, Kaufman HE. Topically applied cyclosporine in zone prolongs corneal allograft survival. Invest Ophthalmol Vis Sci. 1988;29:208–15.

    CAS  PubMed  Google Scholar 

  89. Morimoto K, Nakai T, Morisaka K. Evaluation of permeability enhancement of hydrophilic compounds and macromolecular compounds by bile salts through rabbit corneas in-vitro. J Pharm Pharmacol. 1987;39(2):124–6.

    Article  CAS  PubMed  Google Scholar 

  90. Chiou GCY, Shen ZF, Zheng YQ, Chen YJ. Enhancement of systemic delivery of peptides drug via ocular route with surfactants. Drug Dev Res. 1988;27:177–83.

    Article  Google Scholar 

  91. Yamamoto A, Luo AM, Dodda-Kashi S, Lee VH. The ocular route for systemic insulin delivery in the albino rabbit. J Pharmacol Exp Ther. 1989;249:249–55.

    CAS  PubMed  Google Scholar 

  92. Wang Y, Lin H, Lin S, Qu J, Xiao J, Huang Y, Xiao Y, Fu X, Yang Y, Li X. Cell-penetrating peptide TAT-mediated delivery of acidic FGF to retina and protection against ischemia–reperfusion injury in rats. J Cell Mol Med. 2010;14(7):1998–2005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Lee KY, Yuk SH. Polymeric protein delivery systems. Prog Polym Sci. 2007;32(7):669–97.

    Article  CAS  Google Scholar 

  94. Abrishami M, Zarei-Ghanavati S, Soroush D, Rouhbakhsh M, Jaafari MR, Malaekeh-Nikouei B. Preparation, characterization, and in vivo evaluation of nanoliposomes-encapsulated bevacizumab (avastin) for intravitreal administration. Retina. 2009;29(5):699–703.

    Article  PubMed  Google Scholar 

  95. Gavini E, Chetoni P, Cossu M, Alvarez MG, Saettone MF, Giunchedi P. PLGA microspheres for the ocular delivery of a peptide drug, vancomycin using emulsification/spray-drying as the preparation method: in vitro/in vivo studies. Eur J Pharm Biopharm. 2004;57(2):207–12.

    Article  CAS  PubMed  Google Scholar 

  96. Nair R, Chakrapani M, Kaza R. Preparation and evaluation of vancomycin microemulsion for ocular drug delivery. Drug Deliv Lett. 2012;2(1):26–34.

    CAS  Google Scholar 

  97. Yousry C, Fahmy RH, Essam T, El-Laithy HM, Elkheshen SA. Nanoparticles as tool for enhanced ophthalmic delivery of vancomycin: a multidistrict-based microbiological study, solid lipid nanoparticles formulation and evaluation. Drug Dev Ind Pharm. 2016;42(11):1752–62.

    Article  CAS  PubMed  Google Scholar 

  98. Khangtragool A, Ausayakhun S, Leesawat P, Laokul C, Molloy R. Chitosan as an ocular drug delivery vehicle for vancomycin. J Appl Polym Sci. 2011;122(5):3160–7.

    Article  CAS  Google Scholar 

  99. Ambati J, Gragoudas ES, Miller JW, You TT, Miyamoto K, Delori FC, Adamis AP. Transscleral delivery of bioactive protein to the choroid and retina. Invest Ophthalmol Vis Sci. 2000;41(5):1186–91.

    CAS  PubMed  Google Scholar 

  100. Ranta VP, Urtti A. Transscleral drug delivery to the posterior eye: prospects of pharmacokinetic modeling. Adv Drug Deliv Rev. 2006;58(11):1164–81.

    Article  CAS  PubMed  Google Scholar 

  101. Camelo S, Lajavardi L, Bochot A, Goldenberg B, Naud MC, Brunel N, Lescure B, Klein C, Fattal E, Behar-Cohen F, de Kozak Y. Protective effect of intravitreal injection of vasoactive intestinal peptide-loaded liposomes on experimental autoimmune uveoretinitis. J Ocul Pharmacol Ther. 2009;25(1):9–21.

    Article  CAS  PubMed  Google Scholar 

  102. Nell B, Walde I. Posterior segment diseases. Equine Vet J Suppl. 2010;37:69–79.

    Article  Google Scholar 

  103. Sheardown H, Saltzman WM. Novel drug delivery systems for posterior segment ocular disease. In: Tombrain-Tink J, Barnstable CJ, editors. Ocular angiogenesis. Opthalmology research. New York: Humana Press; 2006.

    Google Scholar 

  104. Ozaki T, Nakazawa M, Yamashita T, Ishiguro S. Delivery of topically applied calpain inhibitory peptide to the posterior segment of the rat eye. PLoS One. 2015;10(6):e0130986.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Ghosh JG, Nguyen AA, Bigelow CE, Poor S, Qiu Y, Rangaswamy N, Ornberg R, Jackson B, Mak H, Ezell T, Kenanova V, de la Cruz E, Carrion A, Etemad-Gilbertson B, Caro RG, Zhu K, George V, Bai J, Sharma-Nahar R, Shen S, Wang Y, Subramanian KK, Fassbender E, Maker M, Hanks S, Vrouvlianis J, Leehy B, Long D, Prentiss M, Kansara V, Jaffee B, Dryja TP, Roguska M. Long-acting protein drugs for the treatment of ocular diseases. Nat Commun. 2017;8:14837.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Liu L, Yu H, Huang X, Tan H, Li S, Luo Y, Zhang L, Jiang S, Jia H, Xiong Y, Zhang R, Huang Y, Chu CC, Tian W. A novel engineered VEGF blocker with an excellent pharmacokinetic profile and robust anti-tumor activity. BMC Cancer. 2015;15:170.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. de Oliveira Dias JR, de Andrade GC, Novais EA, Farah ME, Rodrigues EB. Fusion proteins for treatment of retinal diseases: aflibercept, ziv-aflibercept, and conbercept. Int J Ret Vitr. 2016;2:3.

    Article  Google Scholar 

  108. McCormack PL, Keam SJ. Bevacizumab: a review of its use in metastatic colorectal cancer. Drugs. 2008;68(4):487–506.

    Article  CAS  PubMed  Google Scholar 

  109. Kuppermann BD. A new approach to the rhino in the room. Catar Refr Surg Today. 2014:57–8.

    Google Scholar 

  110. Lu X, Sun X. Profile of conbercept in the treatment of neovascular age-related macular degeneration. Drug Des Devel Ther. 2015;9:2311–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Frokjaer S, Otzen DE. Protein drug stability: a formulation challenge. Nat Rev Drug Discov. 2005;4:298–306.

    Article  CAS  PubMed  Google Scholar 

  112. Rathore N, Rajan RS. Current perspectives on stability of protein drug products during formulation, fill and finish operations. Biotechnol Prog. 2008;24(3):504–14.

    Article  CAS  PubMed  Google Scholar 

  113. Bischof JC, He X. Thermal stability of proteins. Ann N Y Acad Sci. 2005;1066:12–33.

    Article  CAS  PubMed  Google Scholar 

  114. Moreno MR, Tabitha TS, Nirmal J, Radhakrishnan K, Yee CH, Lim S, Venkatraman S, Agrawal R. Study of stability and biophysical characterization of ranibizumab and aflibercept. Eur J Pharm Biopharm. 2016;108:156–67.

    Article  CAS  PubMed  Google Scholar 

  115. Bennett L. Ocular delivery of proteins and peptides. In: Addo R, editor. Ocular drug delivery: advances, challenges and applications. Basel, Switzerland: Springer; 2016.

    Google Scholar 

  116. Yenice I, Mocan MC, Palaska E, Bochot A, Bilensoy E, Vural I, Irkeç M, Hincal AA. Hyaluronic acid coated poly-epsilon-caprolactone nanospheres deliver high concentrations of cyclosporine A into the cornea. Exp Eye Res. 2008;87(3):162–7.

    Article  CAS  PubMed  Google Scholar 

  117. Aksungur P, Demirbilek M, Denkbas EB, Vandervoort J, Ludwig A, Unlü N. Development and characterization of Cyclosporin A loaded nanoparticles for ocular drug delivery: cellular toxicity, uptake, and kinetic studies. J Control Release. 2011;151(3):286–94.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies, St. Augustine, West Indies, Trinidad and Tobago

    Rajiv Dahiya

  2. Department of Pharmaceutical Sciences, School of Pharmacy, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico

    Sunita Dahiya

Authors
  1. Rajiv Dahiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sunita Dahiya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajiv Dahiya .

Editor information

Editors and Affiliations

  1. Faculty of Pharmacy, Sankalchand Patel University, Gujarat, India

    Jayvadan K. Patel

  2. College of Pharmacy, University of South Florida, Tampa, FL, USA

    Vijaykumar Sutariya

  3. School of Medicine, Faculty of Health, Deakin University, Victoria, Australia

    Jagat Rakesh Kanwar

  4. College of Pharmacy, University of South Florida, Tampa, FL, USA

    Yashwant V. Pathak

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Dahiya, R., Dahiya, S. (2018). Ocular Delivery of Peptides and Proteins. In: Patel, J., Sutariya, V., Kanwar, J., Pathak, Y. (eds) Drug Delivery for the Retina and Posterior Segment Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-95807-1_24

Download citation

Publish with us

Policies and ethics

Search

Navigation