Nanotechnology for Transcorneal Drug Targeting in Glaucoma: Challenges and Progress

  • Ameeduzzafar Zafar
  • Javed Ahmad
  • Sohail Akhter
  • Richard T. AddoEmail author


The eye is a highly protected organ, and designing ocular formulation for effective therapy, is challenging for drug delivery researcher. The anatomical and physiological barriers resulted in a low ocular bioavailability of administered drugs. Poor bioavailability of ocularly administered drugs is mainly due to factors responsible for precorneal loss (like tear dynamics, non-productive absorption, a transient residence time in the cul-de-sac, and relative impermeability of the corneal epithelial membrane). Due to these constraints, less than 5 % of the administered dose is absorbed from the conventional ophthalmic dosage forms. Vision-threatening diseases like glaucoma alter the physiology and molecular mechanism of vision. Ocular drug delivery in this dreadful condition is quite challenging. Though, the potential use of a nanoparticulate system as drug carriers has led to the development of many different colloidal delivery vehicles for targeted delivery in glaucoma. Drug loaded colloidal carriers associated with several favorable biological characteristics such as biodegradability, biocompatibility and mucoadhesiveness have been found to be effective in transcorneal drug targeting in glaucoma. These nanoparticulate systems exhibited better ocular drug efficacy by improving ocular bioavailability without blurring the vision in glaucoma. This chapter aims to briefly discuss the ocular barriers to glaucoma drug delivery along with nanotechnology mediated transcorneal drug targeting.


Glaucoma Bioavailability Nanotechnology Colloidal carrier Transcorneal drug targeting 


  1. Addo RT, Siddig A, Patel NJ, Siwale R, Akande J, Uddin AU, D’Souza MJ (2010) Formulation, characterization, and testing of tetracaine hydrochloride-loaded albumin-chitosan microparticles for ocular drug delivery. J Microencapsul 27(2):95–104CrossRefGoogle Scholar
  2. Addo RT, Yeboah KG, Siwale RC, Siddig A, Jones A, Ubale RV, Akande J, Nettey H, Patel NJ, Addo E, D’Souza MJ (2015) Formulation and characterization of atropine sulfate in albumin-chitosan microparticles for in vivo ocular drug delivery. J Pharm Sci 104(5):1677–1690CrossRefGoogle Scholar
  3. Aggarwal D, Pal D, Mitra AK, Kaur IP (2007) Study of the extent of ocular absorption of acetazolamide from a developed niosomal formulation, by microdialysis sampling of aqueous humor. Int J Pharm 338(1–2):21–29CrossRefGoogle Scholar
  4. Akhter S, Talegaonkar S, Khan ZI, Jain GK, Khar RK, Ahmad FJ (2011) Assessment of ocular pharmacokinetics and safety of ganciclovir loaded nanoformulation. Biomed Nanotechnol 7:144–145CrossRefGoogle Scholar
  5. Aksungur P, Demirbilek M, Denkbas EB, Vandervoort J, Ludwig A, Unlu N (2007) Development & characterization of Cyclosporine A loaded nanoparticles for ocular drug delivery: cellular toxicity, uptake, and kinetic studies. J. Control Rel 151:286–294CrossRefGoogle Scholar
  6. Ananthula HK, Vaishya RD, Barot M, Mitra AK (2009) Duane’s Ophthalmology. In: Tasman W, Jaeger EA (eds) Bioavailability. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  7. Bhagav P, Upadhyay H, Chandran S (2011) Brimonidine tartrate-eudragit long-acting nanoparticles: formulation, optimization, in vitro and in vivo evaluation. AAPS PharmSciTech 12(4):1087–1101CrossRefGoogle Scholar
  8. Bourlais CL, Acar L, Zia H, Sado PA, Neehan T et al (1998) Ophthalmic drug delivery systems-recent advances. Prog Retin Eye Res 17(1):33–58Google Scholar
  9. Casson RJ, Chidlow GW, John PM, Crowston JG, Goldberg I (2012) Definition of glaucoma: Clinical and experimental concepts. Clin Exp Ophthalmol 40(4):341–349CrossRefGoogle Scholar
  10. Chen R, Qian Y, Li R, Zhang Q, Liu D, Wang M, Xu Q (2010) Methazolamide calcium phosphate nanoparticles in an ocular delivery system. Yakugaku Zasshi 130(3):419–424CrossRefGoogle Scholar
  11. De-Santis LM Jr (1994) Adrenergic receptor-blocking agents. In: Mauger TF, Craig EL (eds) Havener’s ocular pharmacology, 6th edn. Mosby-Year Book, St Louis, MO, pp 84–112Google Scholar
  12. Dey S, Anand BS, Patel J, Mitra AK (2003a) Transporters/receptors in the anterior chamber: pathways to explore ocular drug delivery strategies. Expert Opin Biol Ther 3(1):23–44CrossRefGoogle Scholar
  13. Dey S, Patel J, Anand BS et al (2003b) Molecular evidence and functional expression of P-glycoprotein (MDR1) in human and rabbit cornea and corneal epithelial cell lines. Invest Ophthalmol Vis Sci 44(7):2909–2918CrossRefGoogle Scholar
  14. Dey S, Gunda S, Mitra AK (2004) Pharmacokinetics of erythromycin in rabbit corneas after single-dose infusion: role of P-glycoprotein as a barrier to in vivo ocular drug absorption. J Pharmacol Exp Ther 311(1):246–255CrossRefGoogle Scholar
  15. Diepold R, Kreuter J, Himber J, Gurny R, Lee VHL, Robinson JR, Saettone MF, Schnaudigel OE (1989) Comparison of different models for the testing of pilocarpine eyedrops using conventional eyedrops as a novel depot formulation (nanoparticles). Graefe’s Arch Clin Exp Ophthalmol 227:188CrossRefGoogle Scholar
  16. Diebold Y, Jarrín M, Sáez V, Carvalho EL, Orea M, Calonge M, Seijo B, Alonso MJ (2007) Ocular drug delivery by liposome-chitosan nanoparticle complexes (LCS-NP). Biomaterials 28(8):1553–1564CrossRefGoogle Scholar
  17. Doina G, Hosking SL, Orgu S (2004) Autonomic nervous system, circadian rhythms, and primary open-angle glaucoma. Surv Ophthalmol 49:491–508CrossRefGoogle Scholar
  18. Duijm HF, van den Berg TJ, Greve EL (1997) Choroidal haemodynamics in glaucoma. Br J Ophthalmol 81:735–742CrossRefGoogle Scholar
  19. Durrani AM, Davies NM, Thomas M, Kellaway IW (1992) Pilocarpine bioavailability from a mucoadhesive liposomal ophthalmic delivery system. Int J Pharm 88(1):409–415Google Scholar
  20. Fessi H, Puisieux F, Devissaguet JP, Ammoury N, Benitas S (1989) Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm 55:R1–R4CrossRefGoogle Scholar
  21. Gaudana R, Jwala J, Boddu SH et al (2009a) Recent perspectives in ocular drug delivery. Pharm Res 26(5):1197–1216CrossRefGoogle Scholar
  22. Gaudana R, Jwala J, Boddu SH, Mitra AK (2009b) Recent perspectives in ocular drug delivery. Pharm Res 26(5):1197–1216CrossRefGoogle Scholar
  23. Geroski DH, Edelhauser HF (2001) Transscleral drug delivery for posterior segment disease. Adv Drug Deliv Rev 52(1):37–48CrossRefGoogle Scholar
  24. Gherghel D, Hosking SL, Orgu S (2004) Autonomic nervous system, circadian rhythms, and primary open-angle glaucoma. Surv Ophthalmol 49:491–508CrossRefGoogle Scholar
  25. Guinedi AS, Mortada ND, Mansour S, Hathout RM (2005) Preparation and evaluation of reverse-phase evaporation and multilamellar niosomes as ophthalmic carriers of acetazolamide. Int J Pharm 306:71–82CrossRefGoogle Scholar
  26. Gupta H, Aqil M, Khar RK, Ali A, Bhatnagar A, Mittal G (2011) Biodegradable levofloxacine nanoparticles for sustained ocular drug delivery. J Drug Target 19(6):409–417CrossRefGoogle Scholar
  27. Gupta H, Aqil M, Khar RK, Ali A, Bhatnagar A, Mittal G (2010) Sparfloxacin-loaded PLGA nanoparticles for sustained ocular drug delivery. Nanomed Nanotech Boil Med 6:324–333CrossRefGoogle Scholar
  28. Hämäläinen KM, Kontturi K, Auriola S, Murtomäki L, Urtti A (1997) Estimation of pore size and pore density of biomembranes from permeability measurements of polyethylene glycols using an effusion-like approach. J Controlled Release 49:97–104Google Scholar
  29. Harima T, Kreuter J, Speiser P, Boye T, Gurny R, Kubis A (1986) Enhancement of miotic response of rabbits with pilocarpine-loaded polybutylcyanoacrylate nanoparticles. Int J Pharm 33:187CrossRefGoogle Scholar
  30. Hathout RM, Mansour S, Mortada ND, Guinedi AS (2007) Liposomes as an ocular delivery system for acetazolamide: in vitro and in vivo studies. AAPS Pharm SciTech 8(1):E1–E12CrossRefGoogle Scholar
  31. Hornof M, Toropainen E, Urtti A (2005) Cell culture models of the ocular barriers. Eur J Pharm Biopharm 60(2):207–225CrossRefGoogle Scholar
  32. Hu FQ, Jiang SP, Du YZ, Yuan H, Ye YQ, Zeng S (2005) Preparation and characterization of stearic acid nanostructured lipid carriers by solvent diffusion method in an aqueous system. Colloids Surf B 45(3–4):167–173CrossRefGoogle Scholar
  33. Huang AJW, Tseng SCG, Kenyon KR (1989) Paracellular permeability of cornea1 and conjunctival epithelia. Invest Ophthalmol Vis Sci 30:684–689PubMedGoogle Scholar
  34. Hyun JJ, Michelle AJ, Carbia BE, Plummer C, Chauhan A (2013) Glaucoma therapy by extended release of timolol from nanoparticle loaded silicone-hydrogel contact lenses. J Control Release 165:82–89CrossRefGoogle Scholar
  35. Jain GK, Pathan SA, Akhter S, Jayabalan N, Talagaonkar S, Khar RK, Ahmad FJ (2011) Microscopic and spectroscopic evaluation of novel PLGA-Chitosan nanoplexes as ocular delivery system. Colloids Surf B Biointerfaces 82(2):397–403. doi: 10.1016/j.colsurfb.2010.09.010CrossRefGoogle Scholar
  36. Jain K, Kumar RS, Sood S, Dhyanandhan G (2013) Betaxolol hydrochloride loaded chitosan nanoparticles for ocular delivery and their anti-glaucoma efficacy. Curr Drug Deliv 10(5):493–499CrossRefGoogle Scholar
  37. Jain S, Thompson JR, Foot B, Tatham A, Eke T (2014) Severe intraocular pressure rise following intravitreal triamcinolone: a national survey to estimate incidence and describe case profiles. Eye (Lond). doi: 10.1038/eye.2013.306CrossRefGoogle Scholar
  38. Jarvinen T, Pate DW, Lain K (2000) Cannabinoids in the treatment of glaucoma. Pharmacol Ther 295:203–220Google Scholar
  39. Javadzadeh Y, Ahadi F, Davaran S, Mohammadi G, Sabzevari A, Adibkia K (2010) Preparation and physicochemical characterization of naproxen-PLGA nanoparticles. Colloids Surf. B Biointerfaces 81:498–502CrossRefGoogle Scholar
  40. Kalam MA, Sultana Y, Ali A, Aqil M, Mishra AK, Chuttani K (2010) Preparation, characterization, and evaluation of gatifloxacin loaded solid lipid nanoparticles as colloidal ocular drug delivery system. J Drug Target 18(3):191–204CrossRefGoogle Scholar
  41. Kao HJ, Lin HR, Lo YL, Yu SP (2006) Characterization of pilocarpine-loaded chitosan/carbopol nanoparticles. J Pharm Pharmacol 58(2):179–186CrossRefGoogle Scholar
  42. Kaur H, Ahuja M, Kumar S, Dilbaghi N (2012) Carboxymethyl tamarind kernel polysaccharide nanoparticles for ophthalmic drug delivery. Int J Biol Macromol 50:833–839CrossRefGoogle Scholar
  43. Kaur IP, Aggarwal D, Singh H, Kakkar S (2010) Improved ocular absorption kinetics of timolol maleate loaded into a bioadhesive niosomal delivery system. Graefes Arch Clin Exp Ophthalmol 248(10):1467–1472. doi: 10.1007/s00417-010-1383-0CrossRefGoogle Scholar
  44. Kaur IP, Garg A, Singla AK, Aggarwal D (2004) Vesicular systems in ocular drug delivery: an overview. Int J Pharm 269:1–14CrossRefGoogle Scholar
  45. Kawazu K, Yamada K, Nakamura M, Ota A (1999) Characterization of cyclosporin A transport in cultured rabbit corneal epithelial cells: P-glycoprotein transport activity and binding to cyclophilin. Invest Ophthalmol Vis Sci 40(8):1738–1744PubMedGoogle Scholar
  46. Kaye GI, Sibley RC, Hoefle FB (1973) Recent studies on the nature and function of the cornea1 endothelial barrier. Exp Eye Res 15:585–613CrossRefGoogle Scholar
  47. Kayseri O, Lemke A, Hernandez-Trejo N (2005) The impact of nanobiotechnology on the development of new drug delivery systems. Curr Pharm Biotechnol 6:3–5CrossRefGoogle Scholar
  48. Kowing D, Messer D, Slagle S, Wasik A (2010) Programs to optimize adherence in glaucoma. Optometry 81:339–350CrossRefGoogle Scholar
  49. Kumari A, Yadav SK, Yadav SC (2010) Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf A 72(1):1–18Google Scholar
  50. Langman MJS, Lancashire RJ, Cheng KK, Stewart PM (2005) Systemic hypertension and glaucoma: mechanisms in common and co-occurrence. Br J Ophthalmol 89(8):960–963CrossRefGoogle Scholar
  51. Lee VH, Robinson JR (1986) Topical ocular drug delivery: recent developments and future challenges. J Ocul Pharm 2:67–108CrossRefGoogle Scholar
  52. Leonardi A, Bucolo C, Drago F, Salomone S, Pignatello R (2014) Cationic solid lipid nanoparticles enhance ocular hypotensive effect of melatonin in rabbit. Int J Pharm 478(1):180–186CrossRefGoogle Scholar
  53. Liaw J, Robinson JR (1992) The effect of polyethylene glycol molecular weight on cornea1 transport and the related influence of penetration enhancers. Int J Pharm 88:125–140CrossRefGoogle Scholar
  54. Liaw J, Robinson JR (1993) Ocular penetration enhancers. In: Mitra AK (ed) Ophthalmic drug delivery systems. Marcel Dekker, New York, pp 369–381Google Scholar
  55. Lin HR, Yu SP, Kuo CJ, Kao HJ, Lo YL, Lin YJ (2007) Pilocarpine-loaded chitosan-PAA nanosuspension for ophthalmic delivery. J Biomater Sci Polym Ed 18(2):205–221CrossRefGoogle Scholar
  56. Losa C, Alonso MJ, Vila JL, Orallo F, Martinez J, Saavedra JA, Pastor JC (1992) Reduction of cardiovascular side effects associated with ocular administration of metipranolol by inclusion in polymeric nanocapsules. J. Ocul Pharmacol 8:191CrossRefGoogle Scholar
  57. Losa C, Marchal-Heussler L, Orallo F, Vila Jato JL, Alonso MJ (1993) Design of new formulations for topical ocular administration: polymeric nanocapsules containing metipranolol. Pharm Res 10:80–87CrossRefGoogle Scholar
  58. Machaand SA, Mitra K (2003) Overview of ocular drug delivery. In: Mitra AK (ed) ophthalmic drug delivery systems, vol 130. Marcel-Dekker, New York, pp 1–12Google Scholar
  59. Mannermaa E, Vellonen KS, Urtti A (2006) Drug transport in corneal epithelium and blood-retina barrier: emerging role of transporters in ocular pharmacokinetics. Adv Drug Deliv Rev 58(11):1136–1163CrossRefGoogle Scholar
  60. Marchal-Haussler L, Fessi H, Devissaguet JP, Hoffman M, Maincent P (1992) Colloidal drug delivery systems for the eye. A comparison of the efficacy of three different polymers: polyisobutylcyanoacrylate, polylactic-coglycolic acid, poly-epsilon-caprolactone. Pharm Sci 2:98Google Scholar
  61. Marchal-Heussler L, Sirbat D, Hoffman M, Maincent P (1993) Poly (caprolactone) nanocapsules in carteolol ophthalmic delivery. Pharm Res 10:386CrossRefGoogle Scholar
  62. Maurice DM, Mishima S (1984) Ocular pharmacokinetics. In: Sears MC (ed) Handbook of experimental pharmacology, vol. 69. Pharmacology of the Eye. Springer-Verlag, Berlin-Heidelberg, pp 19–l16CrossRefGoogle Scholar
  63. Merodio M, Irache JM, Valamanesh F, Mirshahi M (2002) Ocular disposition and tolerance of ganciclovir-loaded albumin nanoparticles after intravitreal injection in rats. Biomaterials 23:1587–1594CrossRefGoogle Scholar
  64. Michelson G, Langhans MJ, Groh MJ (1996) Perfusion of the juxtapapillary retina and the neuroretinal rim area in primary open angle glaucoma. J Glaucoma 5:91–98PubMedGoogle Scholar
  65. Musumeci T, Bucolo C, Carbone C, Pignatello R, Drago F, Puglisi G (2013) Polymeric nanoparticles augment the ocular hypotensive effect of melatonin in rabbits. Int J Pharm 440(2):135–140CrossRefGoogle Scholar
  66. Nathanson JA (1980) Effects of a potent and specific beta 2-adrenoceptor antagonist on intraocular pressure. PNAS, USA 77(12):7420–7424Google Scholar
  67. Newell DG (1986) Monoclonal antibodies directed against the flagella of Campylobacter jejuni: cross-reacting and serotypic specificity and potential use in diagnosis. J Hyg (Lond) 96(3):377–384CrossRefGoogle Scholar
  68. Ohtake Y, Tanino T, Kimura I et al (2004) Long-term efficacy and safety of combines topical antiglaucoma therapy-timolol and unoprostone versus betaxolol and unoprostone. Nippon Ganka Gakkai Zasshi. J Jpn Ophthalmol Soc 108:23–28Google Scholar
  69. Omaima NE, Ahmed HH (1997) Preparation and evaluation of acetazolamide liposomes as an ocular delivery system. Int J Pharm 158:121–125Google Scholar
  70. Papadimitriou S, Bikiaris D, Avgoustakis K, Karavas E, Georgarakis M (2008) Chitosan nanoparticles loaded with dorzolamide and pramipexole. Carbohyd Polym 73(1):44–54CrossRefGoogle Scholar
  71. Parhi R, Suresh P (2010) Production of solid lipid nanoparticles—drug loading and release mechanism. J Chem Pharm Res 2(1):211–227Google Scholar
  72. Piltz-Seymour JR, Grunwald JE, Hariprasad SM, Dupont J (2001) Optic nerve blood flow is diminished in eyes of primary open-angle glaucoma suspects. Am J Ophthalmol 132:63–69CrossRefGoogle Scholar
  73. Quaranta L, Katsanos A, Russo A et al (2013a) 24-hour intraocular pressure and ocular perfusion pressure in glaucoma; major review. Surv Ophthalmol 58:26–40CrossRefGoogle Scholar
  74. Quaranta L, Katsanos A, Russo A, Riva I (2013b) 24-hour intraocular pressure and ocular perfusion pressure in glaucoma; major review. Surv Ophthalmol 58:26–40CrossRefGoogle Scholar
  75. Quigley HA (1996) Number of people with glaucoma worldwide. J Ophthalmol 80:389–393Google Scholar
  76. Quigley HA, Broman AT (2006) The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 90:262–267CrossRefGoogle Scholar
  77. Rapoport SI (1976) Blood-brain barrier in physiology and medicine. Raven Press, New YorkGoogle Scholar
  78. Rhee DJ (2013) Glaucoma. In: Porter RS, Kaplan JL (eds) The Merck manual home health handbook. Retrieved 12 Dec 2013Google Scholar
  79. Sahoo SK, Dilnawaz F, Krishnakumar S (2008) Nanotechnology in ocular drug delivery. Drug Discov Today 13:144–151CrossRefGoogle Scholar
  80. Sahoo SK, Labhasetwar V (2003) Nanotech approaches to drug delivery and imaging. Drug Discov Today 8:1112–1120CrossRefGoogle Scholar
  81. Satilmis M, Orgu S, Doubler B et al (2003) Rate of progression of glaucoma correlates with retrobulbar circulation and intraocular pressure. Am J Ophthalmol 135:664–669CrossRefGoogle Scholar
  82. Saxena R, Prakash J, Mathur P, Gupta SK (2002) Pharmacotherapy of Glaucoma. Indian J Pharmacol 34:71–85Google Scholar
  83. Schoenwald RD (1990) Ocular drug delivery. Pharmacokinetic considerations. Clin. Pharm. 18:255–269CrossRefGoogle Scholar
  84. Seyfoddin A, Shaw J, Al-Kassas R (2010) Solid lipid nanoparticles for ocular drug delivery. Drug Deliv 17(7):467–489CrossRefGoogle Scholar
  85. Shields MB (1992) Adrenergic inhibitors. In: Williams MD (ed) Textbook of glaucoma, 3rd edn. Wilkins, Baltimore, pp 480–499Google Scholar
  86. Singh J, Chhabra G, Pathak K (2014) Development of acetazolamide loaded, pH triggered polymeric nanoparticulate in situ gel for sustained ocular delivery: in vitro, ex vivo evaluation and pharmacodynamic study. Drug Dev Ind Pharm 40(9):1223CrossRefGoogle Scholar
  87. Singh KH, Shinde UA (2011) Chitosan nanoparticles for controlled delivery of brimonidine tartrate to the ocular membrane. Pharmazie 66(8):594–599PubMedGoogle Scholar
  88. Stroman GA, Stewart WC, Golnik KC (1995) Magnetic resonance imaging in patients with low-tension glaucoma. Arch Ophthalmol 113:168–172CrossRefGoogle Scholar
  89. Susanna R, Basseto FL (1992) Hemorrhage of the optic disc and neurosensorial dysacousia. J Glaucoma 1:248–253CrossRefGoogle Scholar
  90. Tataru CP, Purcarea VL (2012) Antiglaucoma pharmacotherapy. J Med Life 5:247–251PubMedPubMedCentralGoogle Scholar
  91. Ticho U, Blumenthal M, Zonis S, Gal A, Blank I, Mazor ZW (1979a) Piloplex, a new long-acting pilocarpine polymer salt. A long-term study. Br J Opthalmol 63:48CrossRefGoogle Scholar
  92. Ticho U, Blumenthal M, Zonis S, Gal A, Blank I, Mazor ZW (1979b) A clinical trial with Piloplex—a new long-acting pilocarpine compound: preliminary report. Ann Ophthalmol 11:555PubMedGoogle Scholar
  93. Uner M, Yener G (2007) Importance of solid lipid nanoparticles (SLN) in various administration routes and future perspectives. Int J Nanomedicine 2(3):289–300PubMedPubMedCentralGoogle Scholar
  94. Urtti A, Pipkin JD, Rork G, Sendo T, Finne U, Repta AJ (1990) Controlled drug delivery for esperimental ocular studies with timolol 2. Ocular and systemic ahsorption in rabbits. Int J Pharm 61:241–249Google Scholar
  95. Urtti A, Rouhiainen H, Kaila T, Saano V (1994) Controlled ocular timolol delivery: systemic absorption and intraocular pressure effects in humans. Pharm Res 11(9):1278–1282Google Scholar
  96. Van Buskirk EM, Cioffi GA (1992) Glaucomatous optic neuropathy. Am J Ophthalmol 113:447–452CrossRefGoogle Scholar
  97. Vandervoort J, Ludwig A (2004) Preparation and evaluation of drug-loaded gelatin nanoparticles for topical ophthalmic use. Eur. J. Biopharm 57:251–261CrossRefGoogle Scholar
  98. Vidmar V, Pepeljnjak S, Jals˘enjak I (1985) The in vivo evaluation of poly (lactic acid) microcapsules of pilocarpine in hydrochloride. J Microen 2:289CrossRefGoogle Scholar
  99. Wadhwa S, Paliwal R, Paliwal SR, Vyas SP (2010) Hyaluronic acid modified chitosan nanoparticles for effective management of glaucoma: development, characterization, and evaluation. J Drug Target 18(4):292–302. doi: 10.3109/10611860903450023CrossRefGoogle Scholar
  100. Wang F, Chen L, Zhang D, Jiang S, Shi K, Huang Y, Li R, Xu Q (2014a) Methazolamide-loaded solid lipid nanoparticles modified with low-molecular weight chitosan for the treatment of glaucoma: vitro and vivo study. J Drug Target 22(9):849–858CrossRefGoogle Scholar
  101. Wang F, Chen L, Jiang S, He J, Zhang X, Peng J, Xu Q, Li R (2014b) Optimization of methazolamide-loaded solid lipid nanoparticles for ophthalmic delivery using Box–Behnken design. J Liposome Res 24(3):171–181CrossRefGoogle Scholar
  102. Warsi MH, Anwar M, Garg V, Jain GK, Talegaonkar S, Ahmad FJ, Khar RK (2014) Dorzolamide-loaded PLGA/vitamin E TPGS nanoparticles for glaucoma therapy: pharmacoscintigraphy study and evaluation of extended ocular hypotensive effect in rabbits. Colloids Surf B Biointerfaces 122:423–431CrossRefGoogle Scholar
  103. Wasutrasawat P, Al-Obaidi H, Gaisford S, Lawrence MJ, Warisnoicharoen W (2013) Drug solubilisation in lipid nanoparticles containing high melting point triglycerides. Eur J Pharm Biopharm 85(3):365–371CrossRefGoogle Scholar
  104. Wenger Y, Schneider RJ, Reddy GR, Kopelman R, Jolliet O, Philbert MA (2011) Tissue distribution and pharmacokinetics of stable polyacrylamide nanoparticles following intravenous injection in the rat. Toxicol Appl Pharmacol 251:181–190CrossRefGoogle Scholar
  105. Zhang R, He R, Qian J, Guo J, Xue K, Yuan YF (2010) Treatment of experimental autoimmune uveoretinitis with intravitreal injection of tacrolimus (FK506) encapsulated in liposomes. Invest Ophth Vis Sci 51(7):3575–3582CrossRefGoogle Scholar
  106. Zhu X, Su M, Tang S, Wang L, Liang X, Meng F, Hong Y, Xu Z (2012) Synthesis of thiolated chitosan and preparation nanoparticles with sodium alginate for ocular drug delivery. Mol. Vis. 18:1973–1982PubMedPubMedCentralGoogle Scholar
  107. Zimmer AK, Chetoni P, Saettone MF, Zerbe H, Kreuter J (1995) Evaluation of pilocarpine-loaded albumin particles as controlled drug delivery systems for the eye. II. Co-administration with bioadhesive and viscous polymers. J Cont Rel 33:31CrossRefGoogle Scholar
  108. Zimmer A, Mutschler E, Lambrecht G, Mayer D, Kreuter J (1994) Pharmacokinetic and Pharmacodynamic aspects of an ophthalmic pilocarpine nanoparticle-delivery-system. Pharm Res 11:1435CrossRefGoogle Scholar
  109. Zimmer AK, Kreuter J, Robinson JR (1991) Studies on the transport pathway of PBCA nanoparticles in ocular tissues. J Microencapsul 8(4):497–504CrossRefGoogle Scholar
  110. Zimmerman TJ (1993) Topical ophthalmic beta blockers: a comparative review. J Ocul Pharmacol 9:373–384CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  • Ameeduzzafar Zafar
    • 1
  • Javed Ahmad
    • 2
  • Sohail Akhter
    • 3
    • 4
  • Richard T. Addo
    • 5
    Email author
  1. 1.Department of Pharmaceutics, Faculty of PharmacyJamia Hamdard UniversityNew DelhiIndia
  2. 2.Department of PharmaceuticsNational Institute of Pharmaceutical Education and Research (NIPER)RaebareliIndia
  3. 3.LE STUDIUM® Loire Valley Institute for Advanced StudiesCentre-Val de LoireFrance
  4. 4.Nucleic Acids Transfer by Non-Viral MethodsCentre de Biophysique MoléculaireOrléansFrance
  5. 5.Department of Pharmaceutical Sciences, School of PharmacyUnion UniversityJacksonUSA

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