Ocular Drug Delivery: Role of Degradable Polymeric Nanocarriers for Ophthalmic Application

Abstract

Ocular drug delivery has been a major challenge for clinical pharmacologists and biomaterial scientists due to intricate and unique anatomical and physiological barriers in the eye. The critical requirement varies from anterior and posterior ocular segments from a drug delivery perspective. Recently, many new drugs with special formulations have been introduced for targeted delivery with modified methods and routes of drug administration to improve drug delivery efficacy. Current developments in nanoformulations of drug carrier systems have become a promising attribute to enhance drug retention/permeation and prolong drug release in ocular tissue. Biodegradable polymers have been explored as the base polymers to prepare nanocarriers for encasing existing drugs to enhance the therapeutic effect with better tissue adherence, prolonged drug action, improved bioavailability, decreased toxicity, and targeted delivery in eye. In this review, we summarized recent studies on sustained ocular drug/gene delivery and emphasized on the nanocarriers made by biodegradable polymers such as liposome, poly lactic-co-glycolic acid (PLGA), chitosan, and gelatin. Moreover, we discussed the bio-distribution of these nanocarriers in the ocular tissue and their therapeutic applications in various ocular diseases.

References 83

1. 1.

   World Health Organization. Blindness and Vision Impairment Prevention.

   Not in our library

2. 2.

   Kels B.D., Grzybowski A., Grant-Kels J.M. Human ocular anatomy. Clin. Dermatol. 2015;33:140-146.

   Not in our library10.1016/j.clindermatol.2014.10.006

3. 3.

   Kolb H. Simple Anatomy of the Retina by Helga Kolb. 2011.

   Not in our library

4. 4.

   Barar J., Asadi M., Mortazavi-Tabatabaei S.A., Omidi Y. Ocular drug delivery; impact of in vitro cell culture models. J. Ophthalmic Vis. Res. 2009;4:238-252.

   Not in our library

5. 5.

   Kiel J.W. The ocular circulation. Colloquium Series on Integrated Systems Physiology: From Molecule to Function. 2011;1-81.

   Not in our library

6. 6.

   Kim Y.C., Chiang B., Wu X., Prausnitz M.R. Ocular delivery of macromolecules. J. Control. Release. 2014;190:172-181.

   Not in our library10.1016/j.jconrel.2014.06.043

7. 7.

   Shintani K., Shechtman D.L., Gurwood A.S. Review and update: Current treatment trends for patients with retinitis pigmentosa. Optometry. 2009;80:384-401.

   Not in our library10.1016/j.optm.2008.01.026

8. 8.

   Del Amo E.M., Urtti A. Current and future ophthalmic drug delivery systems: A shift to the posterior segment. Drug Discov. Today. 2008;13:135-143.

   Not in our library10.1016/j.drudis.2007.11.002

9. 9.

   Sampat K.M., Garg S.J. Complications of intravitreal injections. Curr. Opin. Ophthalmol. 2010;21:178-183.

   Not in our library10.1097/icu.0b013e328338679a

10. 10.

    Jager R.D., Aiello L.P., Patel S.C., Cunningham E.T. Risks of intravitreous injection: A comprehensive review. Retina. 2004;24:676-698.

    Not in our library10.1097/00006982-200410000-00002

11. 11.

    Gerstenblith A.T., Rabinowitz M.P. The Wills Eye Manual: Office and Emergency Room Diagnosis and Treatment of Eye Disease. 2012.

    Not in our library

12. 12.

    Gaudana R., Jwala J., Boddu S.H., Mitra A.K. Recent perspectives in ocular drug delivery. Pharm. Res. 2009;26:1197.

    Not in our library10.1007/s11095-008-9694-0

13. 13.

    Urtti A. Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv. Drug Deliv. Rev. 2006;58:1131-1135.

    Not in our library10.1016/j.addr.2006.07.027

14. 14.

    Chang C.Y., Wang M.C., Miyagawa T., Chen Z.Y., Lin F.H., Chen K.H., Liu G.S., Tseng C.L. Preparation of arginine–glycine–aspartic acid-modified biopolymeric nanoparticles containing epigalloccatechin-3-gallate for targeting vascular endothelial cells to inhibit corneal neovascularization. Int. J. Nanomed. 2017;12:279-294.

    Not in our library10.2147/ijn.s114754

15. 15.

    Ali M., Byrne M.E. Challenges and solutions in topical ocular drug-delivery systems. Expert Rev. Clin. Pharmacol. 2008;1:145-161.

    Not in our library10.1586/17512433.1.1.145

16. 16.

    Tangri P., Khurana S. Basics of ocular drug delivery systems. Int. J. Res. Pharm. 2011;2:1541-1552.

    Not in our library

17. 17.

    Molokhia S.A., Thomas S.C., Garff K.J., Mandell K.J., Wirostko B.M. Anterior eye segment drug delivery systems: Current treatments and future challenges. J. Ocul. Pharmacol. Ther. 2013;29:92-105.

    Not in our library10.1089/jop.2012.0241

18. 18.

    Kuno N., Fujii S. Recent advances in ocular drug delivery systems. Polymers. 2011;3:193-221.

    Not in our library10.3390/polym3010193

19. 19.

    Shivhare R., Pathak A., Shrivastava N., Singh C., Tiwari G., Goyal R. An update review on novel advanced ocular drug delivery system. World J. Pharm. Pharm. Sci. 2012;1:545-568.

    Not in our library

20. 20.

    Tomi M., Hosoya K.-I. The role of blood–ocular barrier transporters in retinal drug disposition: An overview. Expert Opin. Drug Metab. Toxicol. 2010;6:1111-1124.

    Not in our library10.1517/17425255.2010.486401

21. 21.

    Souto E.B., Doktorovova S., Gonzalez-Mira E., Egea M.A., Garcia M.L. Feasibility of lipid nanoparticles for ocular delivery of anti-inflammatory drugs. Curr. Eye Res. 2010;35:537-552.

    Not in our library10.3109/02713681003760168

22. 22.

    Holekamp N.M. The vitreous gel: More than meets the eye. Am. J. Ophthalmol. 2010;149:32-36.

    Not in our library10.1016/j.ajo.2009.07.036

23. 23.

    Thakur S.S., Barnett N.L., Donaldson M.J., Parekh H.S. Intravitreal drug delivery in retinal disease: Are we out of our depth? Expert Opin. Drug Deliv. 2014;11:1575-1590.

    Not in our library10.1517/17425247.2014.927864

24. 24.

    Achouri D., Alhanout K., Piccerelle P., Andrieu V. Recent advances in ocular drug delivery. Drug Dev. Ind. Pharm. 2013;39:1599-1617.

    Not in our library10.3109/03639045.2012.736515

25. 25.

    Gaudana R., Ananthula H.K., Parenky A., Mitra A.K. Ocular drug delivery. AAPS J. 2010;12:348-360.

    Not in our library10.1208/s12248-010-9183-3

26. 26.

    HS Boddu S., Gupta H., Patel S. Drug delivery to the back of the eye following topical administration: An update on research and patenting activity. Recent Pat. Drug Deliv. Formul. 2014;8:27-36.

    Not in our library10.2174/1872211308666140130093301

27. 27.

    Hikichi T., Kado M., Yoshida A. Intravitreal injection of hyaluronidase cannot induce posterior vitreous detachment in the rabbit. Retina. 2000;20:195-198.

    Not in our library10.1097/00006982-200002000-00014

28. 28.

    Martens T.F., Remaut K., Deschout H., Engbersen J.F., Hennink W.E., Van Steenbergen M.J., Demeester J., De Smedt S.C., Braeckmans K. Coating nanocarriers with hyaluronic acid facilitates intravitreal drug delivery for retinal gene therapy. J. Control Release. 2015;202:83-92.

    Not in our library10.1016/j.jconrel.2015.01.030

29. 29.

    Sahoo S.K., Dilnawaz F., Krishnakumar S. Nanotechnology in ocular drug delivery. Drug Discov. Today. 2008;13:144-151.

    Not in our library10.1016/j.drudis.2007.10.021

30. 30.

    Nagarwal R.C., Kant S., Singh P.N., Maiti P., Pandit J.K. Polymeric nanoparticulate system: A potential appproach for ocular drug delivery. J. Control. Release. 2009;136:2-13.

    Not in our library10.1016/j.jconrel.2008.12.018

31. 31.

    Liu S., Jones L., Gu F.X. Nanomaterials for ocular drug delivery. Macromol. Biosci. 2012;12:608-620.

    Not in our library10.1002/mabi.201100419

32. 32.

    Ali Y., Lehmussaari K. Industrial perspective in ocular drug delivery. Adv. Drug Deliv. Rev. 2006;57:1258-1268.

    Not in our library10.1016/j.addr.2006.07.022

33. 33.

    Zhang Q., Li J., Gao W., Zhang L. Nanoparticles for Ocular Drug Delivery. Ophthalmic Disease Mechanisms and Drug Discovery. 2017;197-223.

    Not in our library

34. 34.
    Ocular Drug Delivery Barriers—Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases · 2018

    No notice
35. 35.

    Chen H., Jin Y., Sun L., Li X., Nan K., Liu H., Zheng Q., Wang B. Recent Developments in Ophthalmic Drug Delivery Systems for Therapy of Both Anterior and Posterior Segment Diseases. Colloids Interface Sci. Commun. 2018;24:54-61.

    Not in our library10.1016/j.colcom.2018.03.008

36. 36.

    Reimondez-Troitiño S., Csaba N., Alonso M.J., de la Fuente M. Nanotherapies for the treatment of ocular diseases. Eur. J. Pharm. Biopharm. 2015;95:279-293.

    Not in our library10.1016/j.ejpb.2015.02.019

37. 37.

    Akhter S., Anwar M., Siddiqui M.A., Ahmad I., Ahmad J., Ahmad M.Z., Bhatnagar A., Ahmad F.J. Improving the topical ocular pharmacokinetics of an immunosuppressant agent with mucoadhesive nanoemulsions: Formulation development, in-vitro and in-vivo studies. Colloids Surf. B Biointerfaces. 2016;148:19-29.

    Not in our library10.1016/j.colsurfb.2016.08.048

38. 38.

    Tseng C.L., Chen K.H., Su W.Y., Lee Y.H., Wu C.C., Lin F.H. Cationic Gelatin Nanoparticles for Drug Delivery to the Ocular Surface: In vitro and In vivo Evaluation. J. Nanomater. 2013;2013:1-11.

    Not in our library

39. 39.

    Xu Q., Boylan N.J., Suk J.S., Wang Y.-Y., Nance E.A., Yang J.-C., McDonnell P.J., Cone R.A., Duh E.J., Hanes J. Nanoparticle diffusion in, and microrheology of, the bovine vitreous ex vivo. J. Control. Release. 2013;167:76-84.

    Not in our library10.1016/j.jconrel.2013.01.018

40. 40.

    Ying L., Tahara K., Takeuchi H. Drug delivery to the ocular posterior segment using lipid emulsion via eye drop administration: Effect of emulsion formulations and surface modification. Int. J. Pharm. 2013;453:329-335.

    Not in our library10.1016/j.ijpharm.2013.06.024

41. 41.

    Honary S., Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems—A review (Part 2). Trop. J. Pharm. Res. 2013;12:265-273.

    Not in our library

42. 42.

    Koo H., Moon H., Han H., Na J.H., Huh M.S., Park J.H., Woo S.J., Park K.H., Kwon I.C., Kim K., et al. The movement of self-assembled amphiphilic polymeric nanoparticles in the vitreous and retina after intravitreal injection. Biomaterials. 2012;33:3485-3493.

    Not in our library10.1016/j.biomaterials.2012.01.030

43. 43.

    Kim H., Robinson S.B., Csaky K.G. Investigating the movement of intravitreal human serum albumin nanoparticles in the vitreous and retina. Pharm. Res. 2009;26:329-337.

    Not in our library10.1007/s11095-008-9745-6

44. 44.

    Hagigit T., Abdulrazik M., Valamanesh F., Behar-Cohen F., Benita S. Ocular antisense oligonucleotide delivery by cationic nanoemulsion for improved treatment of ocular neovascularization: An in-vivo study in rats and mice. J. Control. Release. 2012;160:225-231.

    Not in our library10.1016/j.jconrel.2011.11.022

45. 45.

    Kompellaa U.B., Amrited A.C., Ravia R.P., Durazo S.A. Nanomedicines for back of the eye drug delivery, gene delivery, and imaging. Prog. Retin Eye Res. 2013;36:172-198.

    Not in our library10.1016/j.preteyeres.2013.04.001

46. 46.

    Kaur I.P., Kakkar S. Nanotherapy for posterior eye diseases. J. Control. Release. 2014;193:100-112.

    Not in our library10.1016/j.jconrel.2014.05.031

47. 47.

    Joseph R.R., Venkatraman S.S. Drug delivery to the eye: What benefits do nanocarriers offer? Nanomedicine (Lond.). 2017;12:683-702.

    Not in our library10.2217/nnm-2016-0379

48. 48.

    Hillaireau H., Couvreur P. Nanocarriers’ entry into the cell: Relevance to drug delivery. Cell Mol. Life Sci. 2009;66:2873-2896.

    Not in our library10.1007/s00018-009-0053-z

49. 49.

    Adijanto J., Naash M.I. Nanoparticle-based technologies for retinal gene therapy. Eur. J. Pharm. Biopharm. 2015;95:353-367.

    Not in our library10.1016/j.ejpb.2014.12.028

50. 50.

    Jo D.H., Lee T.G., Kim J.H. Nanotechnology and nanotoxicology in retinopathy. Int. J. Mol. Sci. 2011;12:8288-8301.

    Not in our library10.3390/ijms12118288

51. 51.

    Bisht R., Mandal A., Jaiswal J.K., Rupenthal I.D. Nanocarrier mediated retinal drug delivery: Overcoming ocular barriers to treat posterior eye diseases. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2018;10:e1473.

    Not in our library10.1002/wnan.1473

52. 52.

    Mishra B., Patel B.B., Tiwari S. Colloidal nanocarriers: A review on formulation technology, types and applications toward targeted drug delivery. Nanomedicine. 2010;6:9-24.

    Not in our library10.1016/j.nano.2009.04.008

53. 53.

    Karn P.R., Do Kim H., Kang H., Sun B.K., Jin S.-E., Hwang S.-J. Supercritical fluid-mediated liposomes containing cyclosporin A for the treatment of dry eye syndrome in a rabbit model: Comparative study with the conventional cyclosporin A emulsion. Int. J. Nanomed. 2014;9:3791.

    Not in our library10.2147/ijn.s65601

54. 54.

    De Sá F.A.P., Taveira S.F., Gelfuso G.M., Lima E.M., Gratieri T. Liposomal voriconazole (VOR) formulation for improved ocular delivery. Colloids Surf. B Biointerfaces. 2015;133:331-338.

    Not in our library10.1016/j.colsurfb.2015.06.036

55. 55.

    Davis B.M., Normando E.M., Guo L., Turner L.A., Nizari S., O’Shea P., Moss S.E., Somavarapu S., Cordeiro M.F. Topical Delivery of Avastin to the Posterior Segment of the Eye In Vivo Using Annexin A5-associated Liposomes. Small. 2014;10:1575-1584.

    Not in our library10.1002/smll.201303433

56. 56.

    Lajunen T., Hisazumi K., Kanazawa T., Okada H., Seta Y., Yliperttula M., Urtti A., Takashima Y. Topical drug delivery to retinal pigment epithelium with microfluidizer produced small liposomes. Eur. J. Pharm. Sci. 2014;62:23-32.

    Not in our library10.1016/j.ejps.2014.04.018

57. 57.

    Natarajan J.V., Ang M., Darwitan A., Chattopadhyay S., Wong T.T., Venkatraman S.S. Nanomedicine for glaucoma: Liposomes provide sustained release of latanoprost in the eye. Int. J. Nanomed. 2012;7:123-131.

    Not in our library10.2147/ijn.s25468

58. 58.

    Zhang R., He R., Qian J., Guo J., Xue K., Yuan Y.-F. Treatment of experimental autoimmune uveoretinitis with intravitreal injection of tacrolimus (FK506) encapsulated in liposomes. Investig. Ophthalmol. Vis. Sci. 2010;51:3575-3582.

    Not in our library10.1167/iovs.09-4373

59. 59.

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

    Not in our library10.1097/iae.0b013e3181a2f42a

60. 60.

    Baldrick P. The safety of chitosan as a pharmaceutical excipient. Regul. Toxicol. Pharmacol. 2010;56:290-299.

    Not in our library10.1016/j.yrtph.2009.09.015

61. 61.

    Nagpal K., Singh S.K., Mishra D.N. Chitosan nanoparticles: A promising system in novel drug delivery. Pharm. Bull. 2010;58:1423-1430.

    Not in our library10.1248/cpb.58.1423

62. 62.

    Nagarwal R.C., Singh P.N., Kant S., Maiti P., Pandit J.K. Chitosan nanoparticles of 5-fluorouracil for ophthalmic delivery: Characterization, in-vitro and in-vivo study. Pharm. Bull. 2011;59:272-278.

    Not in our library10.1248/cpb.59.272

63. 63.

    Silva N.C., Silva S., Sarmento B., Pintado M. Chitosan nanoparticles for daptomycin delivery in ocular treatment of bacterial endophthalmitis. Drug Deliv. 2015;22:885-893.

    Not in our library10.3109/10717544.2013.858195

64. 64.

    Klausner E.A., Zhang Z., Chapman R.L., Multack R.F., Volin M.V. Ultrapure chitosan oligomers as carriers for corneal gene transfer. Biomaterials. 2010;31:1814-1820.

    Not in our library10.1016/j.biomaterials.2009.10.031

65. 65.

    Mitra R.N., Han Z., Merwin M., Al Taai M., Conley S.M., Naash M.I. Synthesis and characterization of glycol chitosan DNA nanoparticles for retinal gene delivery. Chem. Med. Chem. 2014;9:189-196.

    Not in our library10.1002/cmdc.201300371

66. 66.

    Han T., Nwe N., Furuike T., Tokura S., Tamura H. Methods of N-acetylated chitosan scaffolds and its in vitro biodegradation by lysozyme. J. Biomed. Sci. Eng. 2012;5:15-23.

    Not in our library10.4236/jbise.2012.51003

67. 67.

    Lončarević A., Ivanković M., Rogina A. Lysozyme-Induced Degradation of Chitosan: The Characterisation of Degraded Chitosan Scaffolds. J. Tissue Repair Regen. 2017;1:12-22.

    Not in our library

68. 68.

    Sun X.Y., Xu C., Wu G., Ye Q.S., Wang C.N. Poly(lactic-co-glycolic acid): Applications and future prospects for periodontal tissue regeneration. Polymers. 2017;9:189.

    Not in our library10.3390/polym9060189

69. 69.

    Ulery B.D., Nair L.S., Laurencin C.T. Biomedical applications of biodegradable polymers. J. Polym. Sci. B Polym. Phys. 2011;49:832-964.

    Not in our library10.1002/polb.22259

70. 70.
    Biodegradable nanoparticles are excellent vehicle for site directed in-vivo delivery of drugs and vaccines · 2011

    No notice
71. 71.

    Makadia H.K., Siegel S.J. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers. 2011;3:1377-1397.

    Not in our library10.3390/polym3031377

72. 72.

    Danhier F., Ansorena E., Silva J.M., Coco R., Le Breton A., Préat V. PLGA-based nanoparticles: An overview of biomedical applications. J. Control. Release. 2012;161:505-522.

    Not in our library10.1016/j.jconrel.2012.01.043

73. 73.

    Cañadas C., Alvarado H., Calpena A.C., Silva A.M., Souto E.B., García M.L., Abrego G. In vitro, ex vivo and in vivo characterization of PLGA nanoparticles loading pranoprofen for ocular administration. Int. J. Pharm. 2016;511:719-727.

    Not in our library10.1016/j.ijpharm.2016.07.055

74. 74.

    Ammar H.O., El-Nahhas S., Ghorab M., Salama A. Chitosan/cyclodextrin nanoparticles as drug delivery system. J. Incl. Phenom. Macrocycl. Chem. 2012;72:127-136.

    Not in our library10.1007/s10847-011-9950-5

75. 75.

    Salama A.H., Mahmoud A.A., Kamel R. A novel method for preparing surface-modified fluocinolone acetonide loaded PLGA nanoparticles for ocular use: In vitro and in vivo evaluations. AAPS PharmSciTech. 2016;17:1159-1172.

    Not in our library10.1208/s12249-015-0448-0

76. 76.

    Bisht R., Rupenthal I.D. PLGA nanoparticles for intravitreal peptide delivery: Statistical optimization, characterization and toxicity evaluation. Pharm. Dev. Technol. 2018;23:324-333.

    Not in our library10.1080/10837450.2016.1240184

77. 77.

    Tahara K., Karasawa K., Onodera R., Takeuchi H. Feasibility of drug delivery to the eye’s posterior segment by topical instillation of PLGA nanoparticles. Asian J. Pharm. Sci. 2017;12:394-399.

    Not in our library10.1016/j.ajps.2017.03.002

78. 78.

    Santoro M., Tatara A.M., Mikos A.G. Gelatin carriers for drug and cell delivery in tissue engineering. J. Control. Release. 2014;190:210-218.

    Not in our library10.1016/j.jconrel.2014.04.014

79. 79.

    Elzoghby A.O. Gelatin-based nanoparticles as drug and gene delivery systems: Reviewing three decades of research. J. Control. Release. 2013;172:1075-1091.

    Not in our library10.1016/j.jconrel.2013.09.019

80. 80.

    Jones R.T., Podczeck F., Jones B.E. Gelatin: Manufacture and physico-chemical properties. Pharmaceutical Capsules. UK; Chicago, IL, USA, 2004;46.

    Not in our library

81. 81.

    Hathout R.M., Omran M.K. Gelatin-based particulate systems in ocular drug delivery. Pharm. Dev. Technol. 2016;21:379-386.

    Not in our library10.3109/10837450.2014.999786

82. 82.

    Mahor A., Prajapati S.K., Verma A., Gupta R., Iyer A.K., Kesharwani P. Moxifloxacin loaded gelatin nanoparticles for ocular delivery: Formulation and in-vitro, in-vivo evaluation. J. Colloid Interface Sci. 2016;483:132-138.

    Not in our library10.1016/j.jcis.2016.08.018

83. 83.

    Contreras-Ruiz L., Zorzi G., Hileeto D., Lopez-Garcia A., Calonge M., Seijo B., Sanchez A., Diebold Y. A nanomedicine to treat ocular surface inflammation: Performance on an experimental dry eye murine model. Gene Therapy. 2013;20:467.

    Not in our library10.1038/gt.2012.56

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