Ophthalmic and Otic Drug Administration: Novel Approaches and Challenges

  • Ankita Desai
  • Manish Shukla
  • Furqan Maulvi
  • Ketan Ranch


Disorders of the eye and ear severely influence the life of millions of people worldwide, but management strategies for these disorders present the challenge primarily for the design of formulation and product development. More than 90% of drugs used in various ophthalmic disorders are in the form of conventional formulation that is eye drops; the drugs however applied in the form of topical solution/drops are being washed off by tear drainage/lacrimation, which leads to lower bioavailability in the range of 1–5%. Transport of such topically applied drugs by the use of conventional dosage forms is limited to the ocular tissue, due to unique anatomy and physiology of the eye. To increase the ocular drug bioavailability, effort has been made in the direction of creating the novel drug delivery systems for ophthalmic application. The chapter will basically emphasize on the restrictions with conventional ocular therapy and explore various novel approaches/emerging novel technologies, to improve the ocular bioavailability of drugs to the anterior as well as posterior chamber of the eye. Treatment strategies for inner ear disorders with high safety and efficacy will remain a challenge. The chapter will focus on recent advancement in the field of otic drug delivery along with its potential limitations.


Ophthalmic drug delivery Otic drug delivery Conventional dosage forms Novel approaches Bioavailability 


  1. 1.
    Le Bourlais C, Acar L, Zia H, Sado PA, Needham T, Leverge R (1998) Ophthalmic drug delivery systems—recent advances. Prog Retin Eye Res 17(1):33–58PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Gulsen D, Chauhan A (2004) Ophthalmic drug delivery through contact lenses. Invest Ophthalmol Vis Sci 45(7):2342–2347PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Patel A, Cholkar K, Agrahari V, Mitra AK (2013) Ocular drug delivery systems: an overview. World J Pharmacol 2(2):47PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Ahmed I, Gokhale RD, Shah MV, Patton T (1987) Physicochemical determinants of drug diffusion across the conjunctiva, sclera, and cornea. J Pharm Sci 76(8):583–586PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Ahmed I, Patton TFJI (1987) Disposition of timolol and inulin in the rabbit eye following corneal versus non-corneal absorption. Int J Pharm 38(1–3):9–21CrossRefGoogle Scholar
  6. 6.
    Ahmed I, Patton T (1985) Importance of the noncorneal absorption route in topical ophthalmic drug delivery. Invest Ophthalmol Vis Sci 26(4):584–587PubMedPubMedCentralGoogle Scholar
  7. 7.
    Ahmed I (2003) The noncorneal route in ocular drug delivery. Taylor and Francis, New York, pp 335–364Google Scholar
  8. 8.
    Rojanasakul Y, Robinson JR (1989) Transport mechanisms of the cornea: characterization of barrier permselectivity. Int J Pharm 55(2–3):237–246CrossRefGoogle Scholar
  9. 9.
    Hornof M, Toropainen E, Urtti A (2005) Cell culture models of the ocular barriers. Eur J Pharm Biopharm 60(2):207–225PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Duvvuri S, Majumdar S, Mitra AK (2003) Drug delivery to the retina: challenges and opportunities. Expert Opin Biol Ther 3(1):45–56PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Sunkara G, Kompella UB (2003) Membrane transport processes in the eye. Taylor and Francis, New York, pp 13–58Google Scholar
  12. 12.
    Hämäläinen K, Kananen K, Auriola S, Kontturi K, Urtti A (1997) Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera. Invest Ophthalmol Vis Sci 38(3):627–634PubMedPubMedCentralGoogle Scholar
  13. 13.
    Schoenwald RD (1990) Ocular drug delivery. Clin Pharmacokinet 18(4):255–269PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Rajasekaran A, Kumaran K, Preetha JP, Karthika (2010) A comparative review on conventional and advanced ocular drug delivery formulations. Int J PharmTech Res 2(1):668–674Google Scholar
  15. 15.
    Mainardes RM, Urban MC, Cinto PO, Khalil NM, Chaud MV, Evangelista RC et al (2005) Colloidal carriers for ophthalmic drug delivery. Curr Drug Targets 6(3):363–371PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Gupta H, Aqil M (2012) Contact lenses in ocular therapeutics. Drug Discov Today 17(9–10):522–527PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Gaudana R, Jwala J, Boddu SH, Mitra AK (2009) Recent perspectives in ocular drug delivery. Pharm Res 26(5):1197PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Tangri P, Khurana S (2011) Basics of ocular drug delivery systems. Int J Res Pharmaceut 2(4):1541–1552Google Scholar
  19. 19.
    Akhter S, Talegaonkar S, Khan ZI, Jain GK, Khar RK, Ahmad FJ (2011) Assessment of ocular pharmacokinetics and safety of Ganciclovir loaded nanoformulations. J Biomed Nanotechnol 7(1):144–145PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Gupta H, Aqil M, Khar R, Ali A, Bhatnagar A, Mittal G (2011) Biodegradable levofloxacin nanoparticles for sustained ocular drug delivery. J Drug Target 19(6):409–417PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Papadimitriou S, Bikiaris D, Avgoustakis K, Karavas E, Georgarakis M (2008) Chitosan nanoparticles loaded with dorzolamide and pramipexole. Carbohydr Polym 73(1):44–54CrossRefGoogle Scholar
  22. 22.
    Sahoo SK, Labhasetwar V (2003) Nanotech approaches to drug delivery and imaging. Drug Discov Today 8(24):1112–1120PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Kayser O, Lemke A (2005) Hernandez-Trejo. The impact of nanobiotechnology on the development of new drug delivery systems. Curr Pharm Biotechnol 6(1):3–5PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Mishima S, Gasset A, Klyce S, Baum J (1966) Determination of tear volume and tear flow. Investig Ophthalmol Vis Sci 5(3):264–276Google Scholar
  25. 25.
    Winter KN, Anderson DM, Braun RJ (2010) A model for wetting and evaporation of a post-blink precorneal tear film. Math Med Biol J IMA 27(3):211–225CrossRefGoogle Scholar
  26. 26.
    Craig J (2002) Structure and function of the preocular tear film. In: The tear film: structure, function clinical examination. Butterworth Heinemann, Oxford, pp 18–50CrossRefGoogle Scholar
  27. 27.
    Barar J, Asadi M, Mortazavi-Tabatabaei SA, Omidi Y (2009) Ocular drug delivery; impact of in vitro cell culture models. J Ophthalmic Vis Res 4(4):238PubMedPubMedCentralGoogle Scholar
  28. 28.
    Dua HS, Faraj LA, Said DG, Gray T, Lowe J (2013) Human corneal anatomy redefined: a novel pre-Descemet’s layer (Dua’s layer). Ophthalmology 120(9):1778–1785PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Malhotra M, Majumdar D (2001) Permeation through cornea. Indian J Exp Biol 39(1):11–24PubMedPubMedCentralGoogle Scholar
  30. 30.
    Freddo TF (2001) Shifting the paradigm of the blood–aqueous barrier. Exp Eye Res 73(5):581–592PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Urtti A (2006) Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv Drug Deliv Rev 58(11):1131–1135PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Cunha-Vaz JG (1976) The blood-retinal barriers. Doc Ophthalmol 41(2):287–327PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Kompella UB, Kadam RS, Lee VH (2010) Recent advances in ophthalmic drug delivery. Ther Deliv 1(3):435–456PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Manish K, Kulkarni G (2012) Recent advances in ophthalmic drug delivery system. Int J Pharm Pharm Sci 4:387Google Scholar
  35. 35.
    Barot M, Bagui M, R Gokulgandhi M, K Mitra A (2012) Prodrug strategies in ocular drug delivery. Med Chem 8(4):753–768PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Loftsson T, Masson M (2001) Cyclodextrins in topical drug formulations: theory and practice. Int J Pharm 225(1–2):15–30PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Rabinovich-Guilatt L, Couvreur P, Lambert G, Dubernet C (2004) Cationic vectors in ocular drug delivery. J Drug Target 12(9–10):623–633PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Gaudana R, Ananthula HK, Parenky A, Mitra AK (2010) Ocular drug delivery. AAPS J 12(3):348–360PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Pitkänen L, Ranta V-P, Moilanen H, Urtti A (2005) Permeability of retinal pigment epithelium: effects of permeant molecular weight and lipophilicity. Invest Ophthalmol Vis Sci 46(2):641–646PubMedCrossRefGoogle Scholar
  40. 40.
    InSite Vision DuraSite®. Available online:
  41. 41.
    InSite Vision AzaSite®. Available online:
  42. 42.
    Kymionis GD, Bouzoukis DI, Diakonis VF, Siganos C (2008) Treatment of chronic dry eye: focus on cyclosporine. Clin Ophthalmol 2(4):829PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Diane D-S, Acheampong A (2005) Ocular pharmacokinetics and safety of ciclosporin, a novel topical treatment for dry eye. Clin Pharmacokinet 44(3):247–261CrossRefGoogle Scholar
  44. 44.
    Bucolo C, Melilli B, Piazza C, Zurria M, Drago F (2011) Ocular pharmacokinetics profile of different indomethacin topical formulations. J Ocul Pharmacol Ther 27(6):571–576PubMedCrossRefGoogle Scholar
  45. 45.
    Trivedi R, Kompella UB (2010) Nanomicellar formulations for sustained drug delivery: strategies and underlying principles. Nanomedicine 5(3):485–505PubMedCrossRefGoogle Scholar
  46. 46.
    Vaishya RD, Khurana V, Patel S, Mitra AK (2014) Controlled ocular drug delivery with nanomicelles. Expert Opin Biol Ther 6(5):422–437Google Scholar
  47. 47.
    Cholkar K, Patel A, Dutt Vadlapudi A, K Mitra A (2012) Novel nanomicellar formulation approaches for anterior and posterior segment ocular drug delivery. Recent Pat Nanomed Med Chem 2(2):82–95CrossRefGoogle Scholar
  48. 48.
    Boddu S (2012) Polymeric nanoparticles for ophthalmic drug delivery: an update on research and patenting activity. Recent Pat Nanomed 2:96–112CrossRefGoogle Scholar
  49. 49.
    Rajoria G, Gupta A (2012) In-situ gelling system: a novel approach for ocular drug delivery. Am J Pharmtech Res 2:24–53Google Scholar
  50. 50.
    Ticho U, Blumenthal M, Zonis S, Gal A, Blank I, Mazor Z (1979) A clinical trial with Piloplex--a new long-acting pilocarpine compound: preliminary report. Ann Ophthalmol 11(4):555–561PubMedPubMedCentralGoogle Scholar
  51. 51.
    Zhang L, Li Y, Zhang C, Wang Y, Song C (2009) Pharmacokinetics and tolerance study of intravitreal injection of dexamethasone-loaded nanoparticles in rabbits. Int J Nanomedicine 4:175PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Kim H, Robinson SB, Csaky KG (2009) Investigating the movement of intravitreal human serum albumin nanoparticles in the vitreous and retina. Pharm Res 26(2):329–337PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Patravale V, Date AA, Kulkarni R (2004) Nanosuspensions: a promising drug delivery strategy. J Pharm Pharmacol 56(7):827–840PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Pignatello R, Bucolo C, Ferrara P, Maltese A, Puleo A, Puglisi G (2002) Eudragit RS100® nanosuspensions for the ophthalmic controlled delivery of ibuprofen. Eur J Pharm Sci 16(1–2):53–61PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Dandagi P, Kerur S, Mastiholimath V, Gadad A, Kulkarni A (2010) Polymeric ocular nanosuspension for controlled release of acyclovir: in vitro release and ocular distribution. Iran J Phar Res 8(2):79–86Google Scholar
  56. 56.
    Kassem M, Rahman AA, Ghorab M, Ahmed M, Khalil R (2007) Nanosuspension as an ophthalmic delivery system for certain glucocorticoid drugs. Int J Pharm 340(1–2):126–133PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Ali HS, York P, Ali AM, Blagden N (2011) Hydrocortisone nanosuspensions for ophthalmic delivery: a comparative study between microfluidic nanoprecipitation and wet milling. J Control Release 149(2):175–181PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Schwendener RA (2007) Liposomes in biology and medicine. In: Bio-applications of nanoparticles. Springer, New York, pp 117–128CrossRefGoogle Scholar
  59. 59.
    Mehanna MM, Elmaradny HA, Samaha MW (2010) Mucoadhesive liposomes as ocular delivery system: physical, microbiological, and in vivo assessment. Drug Dev Ind Pharm 36(1):108–118PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Rathore K, Nema R (2009) An insight into ophthalmic drug delivery system. Int J Pharm Sci Drug Res 1(1):1–5Google Scholar
  61. 61.
    Jin J, Zhou KK, Park K, Hu Y, Xu X, Zheng Z et al (2011) Anti-inflammatory and antiangiogenic effects of nanoparticle-mediated delivery of a natural angiogenic inhibitor. Invest Ophthalmol Vis Sci 52(9):6230–6237PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Lallemand F, Daull P, Benita S, Buggage R, Garrigue J-S (2012) Successfully improving ocular drug delivery using the cationic nanoemulsion, novasorb. J Drug Deliv 2012:604204PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Mishra I (2011) Dendrimer: a novel drug delivery system. J Drug Deliv Ther 1(2):70–74Google Scholar
  64. 64.
    Cheng Y, Xu Z, Ma M, Xu T (2008) Dendrimers as drug carriers: applications in different routes of drug administration. J Pharm Sci 97(1):123–143PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Vandamme TF, Brobeck L (2005) Poly (amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide. J Control Release 102(1):23–38PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Yao W, Sun K, Mu H, Liang N, Liu Y, Yao C et al (2010) Preparation and characterization of puerarin–dendrimer complexes as an ocular drug delivery system. Drug Dev Ind Pharm 36(9):1027–1035PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Bague S, Philips B, Garrigue J-s, Rabinovich-Guilatt L, Lambert G, inventors (2012) US8298568, assignee. Oil-in-water type emulsion with low concentration of cationic agent and positive zeta potential 2012, 30 OCTGoogle Scholar
  68. 68.
    Hara H, Takeuchi H, inventors (2015) US20110008421, assignee. Liposome for delivery to posterior segment of eye and pharmaceutical composition for disease in posterior segment of eye 2015, 25 AugustGoogle Scholar
  69. 69.
    Ketelson HA, Dassanayake NL, Carey TC, Meadows DL, inventors (2012) US8097270, assignee. Use of nanoparticles as carriers for biocides in ophthalmic compositions 2012, Jan 17Google Scholar
  70. 70.
    Ravi N, inventor (2012) US8153156B2, assignee. Hydrogel nanocomposites for ophthalmic applicationsGoogle Scholar
  71. 71.
    Carli F, Baronian M, Schmid R, Chiellini E, inventors (2013) US8414904B2, assignee. Ophthalmic oil-in-water emulsions containing prostaglandinsGoogle Scholar
  72. 72.
    Lee S, Yang J, Lee G, Choi B, Ryu J, inventors EP2659903 A2, assignee. Nanoemulsion-type ophthalmic compositionGoogle Scholar
  73. 73.
    Gaillard PJ, Rip J, inventors (2018) WO2017025588A1, assignee. Pegylated lipid nanoparticle with bioactive lipophilic compoundGoogle Scholar
  74. 74.
    Miller SC, Donovan MD (1982) Effect of poloxamer 407 gel on the mitotic activity of pilocarpine nitrate in rabbits. Int J Pharm 12(2–3):147–152CrossRefGoogle Scholar
  75. 75.
    Gurny R, Ibrahim H, Aebi A, Buri P, Wilson C, Washington N et al (1987) Design and evaluation of controlled release systems for the eye. J Control Release 6(1):367–373CrossRefGoogle Scholar
  76. 76.
    Rozier A, Mazuel C, Grove J, Plazonnet B (1989) Gelrite®: a novel, ion-activated, in-situ gelling polymer for ophthalmic vehicles. Effect on bioavailability of timolol. Int J Pharm 57(2):163–168CrossRefGoogle Scholar
  77. 77.
    Ako-Adounvo A-M, Nagarwal RC, Oliveira L, Boddu SHS, Wang XS, Dey S et al (2014) Recent patents on ophthalmic nanoformulations and therapeutic implications. Recent Pat Drug Deliv Formul 8(3):193–201PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Velagaleti P, Anglade E, Khan I, Gilger B, Mitra A (2010) Topical delivery of hydrophobic drugs using a novel mixed nanomicellar technology to treat diseases of the anterior and posterior segments of the eye. Drug Deliv Technol 10(4):42–47Google Scholar
  79. 79.
    Bengani LC, Chauhan A (2013) Extended delivery of an anionic drug by contact lens loaded with a cationic surfactant. Biomaterials 34(11):2814–2821PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Kim J, Conway A, Chauhan A (2008) Extended delivery of ophthalmic drugs by silicone hydrogel contact lenses. Biomaterials 29(14):2259–2269PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Kim J, Chauhan A (2008) Dexamethasone transport and ocular delivery from poly (hydroxyethyl methacrylate) gels. Int J Pharm 353(1–2):205–222PubMedPubMedCentralGoogle Scholar
  82. 82.
    Gulsen D, Li C-C, Chauhan A (2005) Dispersion of DMPC liposomes in contact lenses for ophthalmic drug delivery. Curr Eye Res 30(12):1071–1080PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Gulsen D, Chauhan A (2005) Dispersion of microemulsion drops in HEMA hydrogel: a potential ophthalmic drug delivery vehicle. Int J Pharm 292(1–2):95–117PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Maulvi FA, Lakdawala DH, Shaikh AA, Desai AR, Choksi HH, Vaidya RJ et al (2016) In vitro and in vivo evaluation of novel implantation technology in hydrogel contact lenses for controlled drug delivery. J Control Release 226:47–56PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Maulvi FA, Shaikh AA, Lakdawala DH, Desai AR, Pandya MM, Singhania SS et al (2017) Design and optimization of a novel implantation technology in contact lenses for the treatment of dry eye syndrome: in vitro and in vivo evaluation. Acta Biomater 53:211–221PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Desai AR, Maulvi FA, Pandya MM, Ranch KM, Vyas BA, Shah SA et al (2018) Co-delivery of timolol and hyaluronic acid from semi-circular ring-implanted contact lenses for the treatment of glaucoma: in vitro and in vivo evaluation. Biomater Sci 6(6):1580–1591PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Maulvi FA, Singhania SS, Desai AR, Shukla MR, Tannk AS, Ranch KM et al (2018) Contact lenses with dual drug delivery for the treatment of bacterial conjunctivitis. Int J Pharm 548(1):139–150PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Yasin MN, Svirskis D, Seyfoddin A, Rupenthal ID (2014) Implants for drug delivery to the posterior segment of the eye: a focus on stimuli-responsive and tunable release systems. J Control Release 196:208–221PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Molokhia SA, Sant H, Simonis J, Bishop CJ, Burr RM, Gale BK et al (2010) The capsule drug device: novel approach for drug delivery to the eye. Vis Res 50(7):680–685PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Haghjou N, Soheilian M, Abdekhodaie MJ (2011) Sustained release intraocular drug delivery devices for treatment of uveitis. J Ophthalmic Vis Res 6(4):317PubMedPubMedCentralGoogle Scholar
  91. 91.
    Cho S, Olsen T (2013) Drug delivery to the suprachoroidal space. Taylor Francis Group, Boca Raton, pp 235–258Google Scholar
  92. 92.
    Rzhevskiy AS, Singh TRR, Donnelly RF, Anissimov YG (2018) Microneedles as the technique of drug delivery enhancement in diverse organs and tissues. J Control Release 270:184–202PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Jiang J, Gill HS, Ghate D, McCarey BE, Patel SR, Edelhauser HF et al (2007) Coated microneedles for drug delivery to the eye. Invest Ophthalmol Vis Sci 48(9):4038–4043PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Vadlapudi A, CholKAr K, Dasari S, Mitra AJ (2015) Ocular drug delivery. Jones & Barnett, Burlington, pp 219–263Google Scholar
  95. 95.
    Dorkowski M, Williamson J, Rixon A (2018) A guide to applying IOP-lowering drugs. Rev Optom 155(7):24–34Google Scholar
  96. 96.
    Jokinen M, Leino L, Griffin C, Pitkäkatu I (2016) New solutions for ophthalmic drug delivery using biodegradable silica matrix. OnDrugDelivery 63:28–30Google Scholar
  97. 97.
    Palmer D, PLC MP, Park M, Seaman P (2016) Opsisporin: a long-acting drug delivery approach for uveitis. ONdrugDelivery 2016(63):32–35Google Scholar
  98. 98.
    Brandt JD, Sall K, DuBiner H, Benza R, Alster Y, Walker G et al (2016) Six-month intraocular pressure reduction with a topical bimatoprost ocular insert: results of a phase II randomized controlled study. Ophthalmology 123(8):1685–1694PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Thekkedath R, Barman K, Barman SP (2014) OcuSurf: a nanostructured, membrane-interactive, biphasic ocular drug delivery system for once/day administration of water-insoluble ophthalmic medications. Invest Ophthalmol Vis Sci 55(13):458Google Scholar
  100. 100.
    Young S, Wong M, Tabata Y, Mikos AG (2005) Gelatin as a delivery vehicle for the controlled release of bioactive molecules. J Control Release 109(1–3):256–274PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Vandervoort J, Ludwig A (2004) Preparation and evaluation of drug-loaded gelatin nanoparticles for topical ophthalmic use. Eur J Pharm Biopharm 57(2):251–261PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Leucuta S (1990) Controlled release of nifedipine from gelatin microspheres and microcapsules: in vitro kinetics and pharmacokinetics in man. J Microencapsul 7(2):209–217PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Hussain AA, Higuchi T, Shell JW (1976) Bioerodible ocular device. Google PatentsGoogle Scholar
  104. 104.
    Ros F, Tijl J, Faber J (1991) Bandage lenses: collagen shield vs. hydrogel lens. CLAO J 17(3):187–190PubMedPubMedCentralGoogle Scholar
  105. 105.
    Friedberg ML, Pleyer U, Mondino B (1991) Device drug delivery to the eye: collagen shield’s, iontophoresis, and pumps. Ophthalmology 98(5):725–732PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    De Campos AM, Sánchez A, Alonso MJ (2001) Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to cyclosporin A. Int J Pharm 224(1–2):159–168PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    De Campos AM, Sánchez A, Gref R, Calvo P, Alonso MJ (2003) The effect of a PEG versus a chitosan coating on the interaction of drug colloidal carriers with the ocular mucosa. Eur J Pharm Sci 20(1):73–81PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Bruining MJ, Edelbroek-Hoogendoorn PS, Blaauwgeers HG, Mooy CM, Hendrikse FH, Koole LH (1999) New biodegradable networks of poly (N-vinylpyrrolidinone) designed for controlled nonburst degradation in the vitreous body. J Biomed Mater Res 47(2):189–197PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Hong Y, Chirila TV, Vijayasekaran S, Dalton PD, Tahija SG, Cuypers MJ et al (1996) Crosslinked poly (1-vinyl-2-pyrrolidinone) as a vitreous substitute. J Biomed Mater Res 30(4):441–448PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Hyon SH (2000) Biodegradable poly (lactic acid) microspheres for drug delivery systems. Yonsei Med J 41(6):720–734PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Yasukawa T, Ogura Y, Kimura H, Sakurai E, Tabata Y (2006) Drug delivery from ocular implants. Expert Opin Drug Deliv 3(2):261–273PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Dillen K, Vandervoort J, Van den Mooter G, Ludwig A (2006) Evaluation of ciprofloxacin-loaded Eudragit® RS100 or RL100/PLGA nanoparticles. Int J Pharm 314(1):72–82PubMedCrossRefPubMedCentralGoogle Scholar
  113. 113.
    Yin H, Gong C, Shi S, Liu X, Wei Y, Qian Z (2010) Toxicity evaluation of biodegradable and thermosensitive PEG-PCL-PEG hydrogel as a potential in situ sustained ophthalmic drug delivery system. J Biomed Mater Res 92(1):129–137CrossRefGoogle Scholar
  114. 114.
    Albertsson AC, Carlfors J, Sturesson C (1996) Preparation and characterisation of poly (adipic anhydride) microspheres for ocular drug delivery. J Appl Polym Sci 62(4):695–705CrossRefGoogle Scholar
  115. 115.
    Draize JH, Woodard G, Calvery HO (1944) Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J Pharmacol Exp Ther 82(3):377–390Google Scholar
  116. 116.
    Osguthorpe JD, Nielsen DR (2006) Otitis externa: review and clinical update. Am Fam Physician 74(9):1510–1516PubMedPubMedCentralGoogle Scholar
  117. 117.
    Harmes KM, Blackwood RA, Burrows HL, Cooke JM, Van Harrison R, Passamani PP (2013) Otitis media: diagnosis and treatment. Children 100(8):10Google Scholar
  118. 118.
    Coco AS (2007) Cost-effectiveness analysis of treatment options for acute otitis media. Ann Fam Med 5(1):29–38PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Vio MM, Holme RH (2005) Hearing loss and tinnitus: 250 million people and a US10 billion potential market. Drug Discov Today 10(19):1263–1265PubMedCrossRefPubMedCentralGoogle Scholar
  120. 120.
    Esterberg R, Coffin AB, Ou H, Simon JA, Raible DW, Rubel EW (2013) Fish in a dish: drug discovery for hearing habilitation. Drug Discov Today Dis Model 10(1):e23–ee9CrossRefGoogle Scholar
  121. 121.
    Liu H, Hao J, Li KS (2013) Current strategies for drug delivery to the inner ear. Acta Pharm Sin B 3(2):86–96CrossRefGoogle Scholar
  122. 122.
    Valente F, Astolfi L, Simoni E, Danti S, Franceschini V, Chicca M et al (2017) Nanoparticle drug delivery systems for inner ear therapy: an overview. J Drug Delivery Sci Technol 39:28–35CrossRefGoogle Scholar
  123. 123.
    Jahnke K (1980) Permeability barriers of the inner ear. Fine structure and function. Fortschr Med 98(9):330–336PubMedPubMedCentralGoogle Scholar
  124. 124.
    Saito T, Zhang ZJ, Tokuriki M, Ohtsubo T, Noda I, Shibamori Y et al (2001) Expression of p-glycoprotein is associated with that of multidrug resistance protein 1 (MRP1) in the vestibular labyrinth and endolymphatic sac of the Guinea pig. Neurosci Lett 303(3):189–192PubMedCrossRefPubMedCentralGoogle Scholar
  125. 125.
    Yang J, Wu H, Zhang P, Hou D-M, Chen J, Zhang S-G (2008) The pharmacokinetic profiles of dexamethasone and methylprednisolone concentration in perilymph and plasma following systemic and local administration. Acta Otolaryngol 128(5):496–504PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Salvinelli F, Maurizi M, Calamita S, D’alatri L, Capelli A, Carbone A (1991) The external ear and the tympanic membrane a three-dimensional study. Scand Audiol 20(4):253–256PubMedCrossRefPubMedCentralGoogle Scholar
  127. 127.
    Okuno H, Sando I (1988) Anatomy of the round window: a histopathological study with a graphic reconstruction method. Acta Otolaryngol 106(1–2):55–63PubMedCrossRefPubMedCentralGoogle Scholar
  128. 128.
    Shea PF, Richey PA, Wan JY, Stevens SR (2012) Hearing results and quality of life after streptomycin/dexamethasone perfusion for Meniere’s disease. Laryngoscope 122(1):204–211PubMedCrossRefPubMedCentralGoogle Scholar
  129. 129.
    Sun C, Wang X, Chen D, Lin X, Yu D, Wu H (2016) Dexamethasone loaded nanoparticles exert protective effects against Cisplatin-induced hearing loss by systemic administration. Neurosci Lett 619:142–148PubMedCrossRefPubMedCentralGoogle Scholar
  130. 130.
    Meyer T (2013) Intratympanic treatment for tinnitus: a review. Noise Health 15(63):83PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    Silverstein H, Thompson J, Rosenberg SI, Brown N, Light J (2004) Silverstein MicroWick. Otolaryngol Clin N Am 37(5):1019–1034CrossRefGoogle Scholar
  132. 132.
    Liu X, Li M, Smyth H, Zhang F (2018) Otic drug delivery systems: formulation principles and recent developments. Drug Dev Ind Pharm 44(9):1395–1408PubMedCrossRefPubMedCentralGoogle Scholar
  133. 133.
    Herraiz C, Aparicio JM, Plaza G (2010) Intratympanic drug delivery for the treatment of inner ear diseases. Acta Otorrinolaringol 61(3):225–232CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Ankita Desai
    • 1
  • Manish Shukla
    • 1
  • Furqan Maulvi
    • 1
  • Ketan Ranch
    • 1
  1. 1.Department of Pharmaceutics, Maliba Pharmacy CollegeUka Tarsadia UniversitySuratIndia

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