Skip to main content
SpringerLink
Log in

Ocular Drug Delivery

  • Chapter
  • First Online:
Pharmacologic Therapy of Ocular Disease

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 242))

Abstract

Although the eye is an accessible organ for direct drug application, ocular drug delivery remains a major challenge due to multiple barriers within the eye. Key barriers include static barriers imposed by the cornea, conjunctiva, and retinal pigment epithelium and dynamic barriers including tear turnover and blood and lymphatic clearance mechanisms. Systemic administration by oral and parenteral routes is limited by static blood–tissue barriers that include epithelial and endothelial layers, in addition to rapid vascular clearance mechanisms. Together, the static and dynamic barriers limit the rate and extent of drug delivery to the eye. Thus, there is an ongoing need to identify novel delivery systems and approaches to enhance and sustain ocular drug delivery. This chapter summarizes current and recent experimental approaches for drug delivery to the anterior and posterior segments of the eye.

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 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
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

  • Abdelbary G (2011) Ocular ciprofloxacin hydrochloride mucoadhesive chitosan-coated liposomes. Pharm Dev Technol 16(1):44–56

    Article  CAS  PubMed  Google Scholar 

  • Aciont. Available from: http://www.aciont.com/technologies/visulex

  • Agrawal AK, Das M, Jain S (2012) In situ gel systems as ‘smart’ carriers for sustained ocular drug delivery. Expert Opin Drug Deliv 9(4):383–402

    Article  CAS  PubMed  Google Scholar 

  • Ahmed I, Patton TF (1985) Importance of the noncorneal absorption route in topical ophthalmic drug delivery. Invest Ophthalmol Vis Sci 26(4):584–587

    CAS  PubMed  Google Scholar 

  • Aksungur P, Demirbilek M, Denkbas EB, Vandervoort J, Ludwig A, Unlu N (2011) Development and characterization of cyclosporine A loaded nanoparticles for ocular drug delivery: cellular toxicity, uptake, and kinetic studies. J Control Release 151(3):286–294

    Article  CAS  PubMed  Google Scholar 

  • Amrite AC, Kompella UB (2005) Size-dependent disposition of nanoparticles and microparticles following subconjunctival administration. J Pharm Pharmacol 57(12):1555–1563

    Article  CAS  PubMed  Google Scholar 

  • Amrite AC, Edelhauser HF, Singh SR, Kompella UB (2008) Effect of circulation on the disposition and ocular tissue distribution of 20 nm nanoparticles after periocular administration. Mol Vis 14:150–160

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ang M (2014) Evaluation of a prednisolone acetate-loaded subconjunctival implant for the treatment of recurrent uveitis in a rabbit model. PLoS One 9(8), e97555

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Arakawa Y, Hashida N, Ohguro N, Yamazaki N, Onda M, Matsumoto S et al (2007) Eye-concentrated distribution of dexamethasone carried by sugar-chain modified liposome in experimental autoimmune uveoretinitis mice. Biomed Res 28(6):331–334

    Article  CAS  PubMed  Google Scholar 

  • Aukunuru JV, Sunkara G, Bandi N, Thoreson WB, Kompella UB (2001) Expression of multidrug resistance-associated protein (MRP) in human retinal pigment epithelial cells and its interaction with BAPSG, a novel aldose reductase inhibitor. Pharm Res 18(5):565–572

    Article  CAS  PubMed  Google Scholar 

  • Badawi AA, El-Laithy HM, El Qidra RK, El Mofty H, El dally M (2008) Chitosan based nanocarriers for indomethacin ocular delivery. Arch Pharm Res 31(8):1040–1049

    Article  CAS  PubMed  Google Scholar 

  • Barar J, Javadzadeh AR, Omidi Y (2008) Ocular novel drug delivery: impacts of membranes and barriers. Expert Opin Drug Deliv 5(5):567–581

    Article  CAS  PubMed  Google Scholar 

  • Baydoun L, Muller-Goymann CC (2003) Influence of n-octenylsuccinate starch on in vitro permeation of sodium diclofenac across excised porcine cornea in comparison to Voltaren ophtha. Eur J Pharm Biopharm 56(1):73–79

    Article  CAS  PubMed  Google Scholar 

  • 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):1087–1101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bikbova G, Bikbov M (2014) Transepithelial corneal collagen cross-linking by iontophoresis of riboflavin. Acta Ophthalmol 92(1):e30–e34

    Article  CAS  PubMed  Google Scholar 

  • Bock F, Matthaei M, Reinhard T, Bohringer D, Christoph J, Ganslandt T et al (2014) High-dose subconjunctival cyclosporine A implants do not affect corneal neovascularization after high-risk keratoplasty. Ophthalmology 121(9):1677–1682

    Article  PubMed  Google Scholar 

  • Bourges JL, Bloquel C, Thomas A, Froussart F, Bochot A, Azan F et al (2006) Intraocular implants for extended drug delivery: therapeutic applications. Adv Drug Deliv Rev 58(11):1182–1202

    Article  CAS  PubMed  Google Scholar 

  • Bourkiza R, Lee V (2012) A review of the complications of lacrimal occlusion with punctal and canalicular plugs. Orbit 31(2):86–93

    Article  PubMed  Google Scholar 

  • Bratton ML, He YG, Weakley DR (2014) Dexamethasone intravitreal implant (Ozurdex) for the treatment of pediatric uveitis. J AAPOS 18(2):110–113

    Article  PubMed  Google Scholar 

  • Calvo P, Alonso MJ, Vila-Jato JL, Robinson JR (1996) Improved ocular bioavailability of indomethacin by novel ocular drug carriers. J Pharm Pharmacol 48(11):1147–1152

    Article  CAS  PubMed  Google Scholar 

  • Carmen AL, Fernando Y, Rafael BI, Angel C (2006) Imprinted soft contact lenses as norfloxacin delivery systems. J Control Release 113:236–424

    Article  CAS  Google Scholar 

  • Chaiyasan W, Srinivas SP, Tiyaboonchai W (2013) Mucoadhesive chitosan-dextran sulfate nanoparticles for sustained drug delivery to the ocular surface. J Ocul Pharmacol Ther 29(2):200–207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang SC, Bundgaard H, Buur A, Lee VH (1987) Improved corneal penetration of timolol by prodrugs as a means to reduce systemic drug load. Invest Ophthalmol Vis Sci 28(3):487–491

    CAS  PubMed  Google Scholar 

  • Chastain JE, Sanders ME, Curtis MA, Chemuturi NV, Gadd ME, Kapin MA et al (2016) Distribution of topical ocular nepafenac and its active metabolite amfenac to the posterior segment of the eye. Exp Eye Res 145:58–67

    Article  CAS  PubMed  Google Scholar 

  • Chauhan A (2015) Ocular drug delivery role of contact lenses. Allied Ophthal Sci 26(2):131–135

    Google Scholar 

  • Chee SP (2012) Moxifloxacin punctum plug for sustained drug delivery. J Ocul Pharmacol Ther 28(4):340–349

    Article  CAS  PubMed  Google Scholar 

  • Cheruvu NP, Kompella UB (2006) Bovine and porcine transscleral solute transport: influence of lipophilicity and the Choroid-Bruch’s layer. Invest Ophthalmol Vis Sci 47(10):4513–4522

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheruvu NP, Amrite AC, Kompella UB (2008) Effect of eye pigmentation on transscleral drug delivery. Invest Ophthalmol Vis Sci 49(1):333–341

    Article  PubMed  PubMed Central  Google Scholar 

  • Chien DS, Tang-Liu DD, Woodward DF (1997) Ocular penetration and bioconversion of prostaglandin F2alpha prodrugs in rabbit cornea and conjunctiva. J Pharm Sci 86(10):1180–1186

    Article  CAS  PubMed  Google Scholar 

  • Chopra P, Hao J, Li SK (2010) Iontophoretic transport of charged macromolecules across human sclera. Int J Pharm 388(1–2):107–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Christie JG, Kompella UB (2008) Ophthalmic light sensitive nanocarrier systems. Drug Discov Today 13(3–4):124–134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Civiale C, Bucaria F, Piazza S, Peri O, Miano F, Enea V (2004) Ocular permeability screening of dexamethasone esters through combined cellular and tissue systems. J Ocul Pharmacol Ther 20(1):75–84

    Article  CAS  PubMed  Google Scholar 

  • Civiale C, Licciardi M, Cavallaro G, Giammona G, Mazzone MG (2009) Polyhydroxyethylaspartamide-based micelles for ocular drug delivery. Int J Pharm 378(1–2):177–186

    Article  CAS  PubMed  Google Scholar 

  • Cohen AE, Assang C, Patane MA, From S, Korenfeld M (2012) Avion study investigators. Evaluation of dexamethasone phosphate delivered by ocular iontophoresis for treating noninfectious anterior uveitis. Ophthalmology 119(1):66–73

    Article  PubMed  Google Scholar 

  • Contreras-Ruiz L, Zorzi GK, Hileeto D, Lopez-Garcia A, Calonge M, Seijo B et al (2013) A nanomedicine to treat ocular surface inflammation: performance on an experimental dry eye murine model. Gene Ther 20(5):467–477

    Article  CAS  PubMed  Google Scholar 

  • Cruysberg LP, Nuijts RM, Geroski DH, Koole LH, Hendrikse F, Edelhauser HF (2002) In vitro human scleral permeability of fluorescein, dexamethasone-fluorescein, methotrexate-fluorescein and rhodamine 6G and the use of a coated coil as a new drug delivery system. J Ocul Pharmacol Ther 18(6):559–569

    Article  CAS  PubMed  Google Scholar 

  • Davies NM (2000) Biopharmaceutical considerations in topical ocular drug delivery. Clin Exp Pharmacol Physiol 27(7):558–562

    Article  CAS  PubMed  Google Scholar 

  • Davies JB, Ciavatta VT, Boatright JH, Nickerson JM (2003) Delivery of several forms of DNA, DNA-RNA hybrids, and dyes across human sclera by electrical fields. Mol Vis 9(68–69):569–578

    CAS  PubMed  Google Scholar 

  • Davis BM, Normando EM, Guo L, Turner LA, Nizari S, O’Shea P et al (2014) Topical delivery of Avastin to the posterior segment of the eye in vivo using annexin A5-associated liposomes. Small 10(8):1575–1584

    Article  CAS  PubMed  Google Scholar 

  • De Campos AM, Sanchez 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):159–168

    Article  PubMed  Google Scholar 

  • de Paiva CS, Schwartz CE, Gjorstrup P, Pflugfelder SC (2012) Resolvin E1 (RX-10001) reduces corneal epithelial barrier disruption and protects against goblet cell loss in a murine model of dry eye. Cornea 31(11):1299–1303

    Article  PubMed  Google Scholar 

  • Dey S, Anand BS, Patel J, Mitra AK (2003) Transporters/receptors in the anterior chamber: pathways to explore ocular drug delivery strategies. Expert Opin Biol Ther 3(1):23–44

    Article  CAS  PubMed  Google Scholar 

  • Di Tommaso C, Torriglia A, Furrer P, Behar-Cohen F, Gurny R, Moller M (2011) Ocular biocompatibility of novel cyclosporin A formulations based on methoxy poly(ethylene glycol)-hexylsubstituted poly(lactide) micelle carriers. Int J Pharm 416(2):515–524

    Article  PubMed  CAS  Google Scholar 

  • Dong Y, Dong P, Huang D, Mei L, Xia Y, Wang Z et al (2015) Fabrication and characterization of silk fibroin-coated liposomes for ocular drug delivery. Eur J Pharm Biopharm 91:82–90

    Article  CAS  PubMed  Google Scholar 

  • Dunlevy JR, Rada JA (2004) Interaction of lumican with aggrecan in the aging human sclera. Invest Ophthalmol Vis Sci 45(11):3849–3856

    Article  PubMed  Google Scholar 

  • Durairaj C, Shah JC, Senapati S, Kompella UB (2009a) Prediction of vitreal half-life based on drug physicochemical properties: quantitative structure-pharmacokinetic relationships (QSPKR). Pharm Res 26(5):1236–1260

    Article  CAS  PubMed  Google Scholar 

  • Durairaj C, Kim SJ, Edelhauser HF, Shah JC, Kompella UB (2009b) Influence of dosage form on the intravitreal pharmacokinetics of diclofenac. Invest Ophthalmol Vis Sci 50(10):4887–4897

    Article  PubMed  PubMed Central  Google Scholar 

  • Durairaj C, Kadam RS, Chandler JW, Hutcherson SL, Kompella UB (2010) Nanosized dendritic polyguanidilyated translocators for enhanced solubility, permeability, and delivery of gatifloxacin. Invest Ophthalmol Vis Sci 51(11):5804–5816

    Article  PubMed  Google Scholar 

  • Duvvuri S, Majumdar S, Mitra AK (2003) Drug delivery to the retina: challenges and opportunities. Expert Opin Biol Ther 3(1):45–56

    Article  CAS  PubMed  Google Scholar 

  • Eljarrat-Binstock E, Domb AJ (2006) Iontophoresis: a non-invasive ocular drug delivery. J Control Release 110(3):479–489

    Article  CAS  PubMed  Google Scholar 

  • Eljarrat-Binstock E, Pe’er J, Domb AJ (2010) New techniques for drug delivery to the posterior eye segment. Pharm Res 27(4):530–543

    Article  CAS  PubMed  Google Scholar 

  • Eperon S, Bossy-Nobs L, Petropoulos IK, Gurny R, Guex-Crosier Y (2008) A biodegradable drug delivery system for the treatment of postoperative inflammation. Int J Pharm 352(1–2):240–247

    Article  CAS  PubMed  Google Scholar 

  • Eytan GD, Kuchel PW (1999) Mechanism of action of P-glycoprotein in relation to passive membrane permeation. Int Rev Cytol 190:175–250

    Article  CAS  PubMed  Google Scholar 

  • Fujisawa T, Miyai H, Hironaka K, Tsukamoto T, Tahara K, Tozuka Y et al (2012) Liposomal diclofenac eye drop formulations targeting the retina: formulation stability improvement using surface modification of liposomes. Int J Pharm 436(1–2):564–567

    Article  CAS  PubMed  Google Scholar 

  • Furrer E, Berdugo M, Stella C, Behar-Cohen F, Gurny R, Feige U et al (2009) Pharmacokinetics and posterior segment biodistribution of ESBA105, an anti-TNF-alpha single-chain antibody, upon topical administration to the rabbit eye. Invest Ophthalmol Vis Sci 50(2):771–778

    Article  PubMed  Google Scholar 

  • Gan L, Gan Y, Zhu C, Zhang X, Zhu J (2009) Novel microemulsion in situ electrolyte-triggered gelling system for ophthalmic delivery of lipophilic cyclosporine A: in vitro and in vivo results. Int J Pharm 365(1–2):143–149

    Article  CAS  PubMed  Google Scholar 

  • Gan L, Han S, Shen J, Zhu J, Zhu C, Zhang X et al (2010) Self-assembled liquid crystalline nanoparticles as a novel ophthalmic delivery system for dexamethasone: improving preocular retention and ocular bioavailability. Int J Pharm 396(1–2):179–187

    Article  CAS  PubMed  Google Scholar 

  • Gaudana R, Jwala J, Boddu SHS, Mitra AK (2009) Recent perspectives in ocular drug delivery. Pharm Res 26(5):1197–1216

    Article  CAS  PubMed  Google Scholar 

  • Gaudana R, Ananthula HK, Parenky A, Mitra AK (2010) Ocular drug delivery. AAPS J 12(3):348–360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghate D, Edelhauser HF (2006) Ocular drug delivery. Expert Opin Drug Deliv 3(2):275–287

    Article  CAS  PubMed  Google Scholar 

  • Ghazi NG, Abboud EB, Nowilaty SR, Alkuraya H, Alhommadi A, Cai H et al (2016) Treatment of retinitis pigmentosa due to MERTK mutations by ocular subretinal injection of adeno-associated virus gene vector: results of a phase I trial. Hum Genet 135(3):327–343

    Article  CAS  PubMed  Google Scholar 

  • Gilger BC, Abarca EM, Salmon JH, Patel S (2013) Treatment of acute posterior uveitis in a porcine model by injection of triamcinolone acetonide into the suprachoroidal space using microneedles. Invest Ophthalmol Vis Sci 54(4):2483–2492

    Article  CAS  PubMed  Google Scholar 

  • Gu JM, Robinson JR, Leung SH (1988) Binding of acrylic polymers to mucin/epithelial surfaces: structure-property relationships. Crit Rev Ther Drug Carrier Syst 5(1):21–67

    CAS  PubMed  Google Scholar 

  • Guidetti B, Azema J, Malet-Martino M, Martino R (2008) Delivery systems for the treatment of proliferative vitreoretinopathy: materials, devices and colloidal carriers. Curr Drug Deliv 5(1):7–19

    Article  CAS  PubMed  Google Scholar 

  • Gupta C, Chauhan A (2011) Ophthalmic delivery of cyclosporine A by punctal plugs. J Control Release 150(1):70–76

    Article  CAS  PubMed  Google Scholar 

  • Gupta AK, Madan S, Majumdar DK, Maitra A (2000) Ketorolac entrapped in polymeric micelles: preparation, characterisation and ocular anti-inflammatory studies. Int J Pharm 209(1–2):1–14

    Article  CAS  PubMed  Google Scholar 

  • Gupta H, Aqil M, Khar RK, Ali A, Bhatnagar A, Mittal G (2011) Biodegradable levofloxacin nanoparticles for sustained ocular drug delivery. J Drug Target 19(6):409–417

    Article  CAS  PubMed  Google Scholar 

  • Habib FS, Fouad EA, Abdel-Rhaman MS, Fathalla D (2010) Liposomes as an ocular delivery system of fluconazole: in-vitro studies. Acta Ophthalmol 88(8):901–904

    Article  CAS  PubMed  Google Scholar 

  • Halhal M, Renard G, Courtois Y, BenEzra D, Behar-Cohen F (2004) Iontophoresis: from the lab to the bed side. Exp Eye Res 78:751–757

    Article  CAS  PubMed  Google Scholar 

  • Hauswirth WW, Aleman TS, Kaushal S, Cideciyan AV, Schwartz SB, Wang L et al (2008) Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum Gene Ther 19(10):979–990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hillman JS (1974) Management of acute glaucoma with pilocarpine-soaked hydrophilic lens. Br J Ophthalmol 58(7):674–679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hobden JA, Reidy JJ, O’Callaghan RJ, Insler MS, Hill JM (1990) Ciprofloxacin iontophoresis for aminoglycoside-resistant pseudomonal keratitis. Invest Ophthalmol Vis Sci 31(10):1940–1944

    CAS  PubMed  Google Scholar 

  • Holden CA, Tyagi P, Thakur A, Kadam R, Jadhav G, Kompella UB et al (2012) Polyamidoamine dendrimer hydrogel for enhanced delivery of antiglaucoma drugs. Nanomed Nanotechnol Biol Med 8(5):776–783

    Article  CAS  Google Scholar 

  • Horvat G, Budai-Szucs M, Berko S, Szabo-Revesz P, Soos J, Facsko A et al (2015) Comparative study of nanosized cross-linked sodium-, linear sodium- and zinc-hyaluronate as potential ocular mucoadhesive drug delivery systems. Int J Pharm 494(1):321–328

    Article  CAS  PubMed  Google Scholar 

  • Hosoya K, Lee VH (1997) Cidofovir transport in the pigmented rabbit conjunctiva. Curr Eye Res 16(7):693–697

    Article  CAS  PubMed  Google Scholar 

  • Hosoya K, Tachikawa M (2012) The inner blood-retinal barrier: molecular structure and transport biology. Adv Exp Med Biol 763:85–104

    CAS  PubMed  Google Scholar 

  • Hosoya K, Horibe Y, Kim KJ, Lee VH (1997) Na(+)-dependent L-arginine transport in the pigmented rabbit conjunctiva. Exp Eye Res 65(4):547–553

    Article  CAS  PubMed  Google Scholar 

  • Hosoya K, Lee VH, Kim KJ (2005) Roles of the conjunctiva in ocular drug delivery: a review of conjunctival transport mechanisms and their regulation. Eur J Pharm Biopharm 60(2):227–240

    Article  CAS  PubMed  Google Scholar 

  • Hosoya K, Tomi M, Tachikawa M (2011) Strategies for therapy of retinal diseases using systemic drug delivery: relevance of transporters at the blood-retinal barrier. Expert Opin Drug Deliv 8(12):1571–1587

    Article  CAS  PubMed  Google Scholar 

  • Hsu KH, Carbia BE, Plummer C, Chauhan A (2015) Dual drug delivery from vitamin E loaded contact lenses for glaucoma therapy. Eur J Pharm Biopharm 94:312–321

    Article  CAS  PubMed  Google Scholar 

  • Hu FQ, Li YH, Yuan H, Zeng S (2006) Novel self-aggregates of chitosan oligosaccharide grafted stearic acid: preparation, characterization and protein association. Pharmazie 61(3):194–198

    CAS  PubMed  Google Scholar 

  • Huang Z (2005) A review of progress in clinical photodynamic therapy. Technol Cancer Res Treat 4(3):283–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes PM, Mitra AK (1993) Effect of acylation on the ocular disposition of acyclovir. II: corneal permeability and anti-HSV 1 activity of 2′-esters in rabbit epithelial keratitis. J Ocul Pharmacol 9(4):299–309

    Article  CAS  PubMed  Google Scholar 

  • Hughes PM, Olejnik O, Chang-Lin JE, Wilson CG (2005) Topical and systemic drug delivery to the posterior segments. Adv Drug Deliv Rev 57(14):2010–2032

    Article  CAS  PubMed  Google Scholar 

  • Hui A, Sheardown H, Jones L (2012) Acetic and acrylic acid molecular imprinted model silicone hydrogel materials for ciprofloxacin-hcl delivery. Materials 5(1):81–107

    Google Scholar 

  • Ibrahim HK, El-Leithy IS, Makky AA (2010) Mucoadhesive nanoparticles as carrier systems for prolonged ocular delivery of gatifloxacin/prednisolone bitherapy. Mol Pharm 7(2):576–585

    Article  CAS  PubMed  Google Scholar 

  • Ideta R, Tasaka F, Jang WD, Nishiyama N, Zhang GD, Harada A et al (2005) Nanotechnology-based photodynamic therapy for neovascular disease using a supramolecular nanocarrier loaded with a dendritic photosensitizer. Nano Lett 5(12):2426–2431

    Article  CAS  PubMed  Google Scholar 

  • Jackson TL, Antcliff R, Hillenkamp J, Marshall J (2003) Human retinal molecular weight exclusion limit and estimate of species variation. Invest Ophthalmol Vis Sci 44(5):2141–2146

    Article  PubMed  Google Scholar 

  • Jaffe GJ, Martin D, Callanan D, Pearson PA, Levy B, Comstock T et al (2006) Fluocinolone acetonide implant (Retisert) for noninfectious posterior uveitis - thirty-four-week results of a multicenter randomized clinical study. Ophthalmology 113(6):1020–1027

    Article  PubMed  Google Scholar 

  • Jain-Vakkalagadda B, Dey S, Pal D, Mitra AK (2003) Identification and functional characterization of a Na+-independent large neutral amino acid transporter, LAT1, in human and rabbit cornea. Invest Ophthalmol Vis Sci 44(7):2919–2927

    Article  PubMed  Google Scholar 

  • Jain-Vakkalagadda B, Pal D, Gunda S, Nashed Y, Ganapathy V, Mitra AK (2004) Identification of a Na+-dependent cationic and neutral amino acid transporter, B(0,+), in human and rabbit cornea. Mol Pharm 1(5):338–346

    Article  CAS  PubMed  Google Scholar 

  • Janoria KG, Hariharan S, Paturi D, Pal D, Mitra AK (2006) Biotin uptake by rabbit corneal epithelial cells: role of sodium-dependent multivitamin transporter (SMVT). Curr Eye Res 31(10):797–809

    Article  CAS  PubMed  Google Scholar 

  • Jiang J, Moore JS, Edelhauser HF, Prausnitz MR (2009) Intrascleral drug delivery to the eye using hollow microneedles. Pharm Res 26(2):395–403

    Article  CAS  PubMed  Google Scholar 

  • Jung HJ, Chauhan A (2012) Temperature sensitive contact lenses for triggered ophthalmic drug delivery. Biomaterials 33(7):2289–2300

    Article  CAS  PubMed  Google Scholar 

  • Kambhampati SP, Mishra MK, Mastorakos P, Oh Y, Lutty GA, Kannan RM (2015) Intracellular delivery of dendrimer triamcinolone acetonide conjugates into microglial and human retinal pigment epithelial cells. Eur J Pharm Biopharm 95(Pt B):239–249

    Google Scholar 

  • Kang SJ, Durairaj C, Kompella UB, O’Brien JM, Grossniklaus HE (2009) Subconjunctival nanoparticle carboplatin in the treatment of murine retinoblastoma. Arch Ophthalmol 127(8):1043–1047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karlgard CC, Wong NS, Jones LW, Moresoli C (2003) In vitro uptake and release studies of ocular pharmaceutical agents by silicon-containing and p-HEMA hydrogel contact lens materials. Int J Pharm 257(1–2):141–151

    Article  CAS  PubMed  Google Scholar 

  • Karn PR, Kim HD, Kang H, Sun BK, Jin SE, Hwang SJ (2014) 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 Nanomedicine 9:3791–3800

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kassem MA, Abdel Rahman AA, Ghorab MM, Ahmed MB, Khalil RM (2007) Nanosuspension as an ophthalmic delivery system for certain glucocorticoid drugs. Int J Pharm 340(1–2):126–133

    Article  CAS  PubMed  Google Scholar 

  • Katiyar S, Pandit J, Mondal RS, Mishra AK, Chuttani K, Aqil M et al (2014) In situ gelling dorzolamide loaded chitosan nanoparticles for the treatment of glaucoma. Carbohydr Polym 102:117–124

    Article  CAS  PubMed  Google Scholar 

  • Katragadda S, Talluri RS, Mitra AK (2006) Modulation of P-glycoprotein-mediated efflux by prodrug derivatization: an approach involving peptide transporter-mediated influx across rabbit cornea. J Ocul Pharmacol Ther 22(2):110–120

    Article  CAS  PubMed  Google Scholar 

  • Kaur IP, Smitha R (2002) Penetration enhancers and ocular bioadhesives: two new avenues for ophthalmic drug delivery. Drug Dev Ind Pharm 28(4):353–369

    Article  CAS  PubMed  Google Scholar 

  • Kempen JH, Altaweel MM, Holbrook JT, Jabs DA, Louis TA, Sugar EA et al (2011) Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial. Ophthalmology 118(10):1916–1926

    Article  PubMed  PubMed Central  Google Scholar 

  • Khan W, Aldouby YH, Avramoff A, Domb AJ (2012) Cyclosporin nanosphere formulation for ophthalmic administration. Int J Pharm 437(1–2):275–276

    Article  CAS  PubMed  Google Scholar 

  • Khurana RN, Appa SN, McCannel CA, Elman MJ, Wittenberg SE, Parks DJ et al (2014) Dexamethasone implant anterior chamber migration risk factors, complications, and management strategies. Ophthalmology 121(1):67–71

    Article  PubMed  Google Scholar 

  • Kim SH, Lutz RJ, Wang NS, Robinson MR (2007) Transport barriers in transscleral drug delivery for retinal diseases. Ophthalmic Res 39(5):244–254

    Article  CAS  PubMed  Google Scholar 

  • Kirchhof S, Goepferich AM, Brandl FP (2015) Hydrogels in ophthalmic applications. Eur J Pharm Biopharm 95(Pt B):227–238

    Google Scholar 

  • Klang S, Abdulrazik M, Benita S (2000) Influence of emulsion droplet surface charge on indomethacin ocular tissue distribution. Pharm Dev Technol 5(4):521–532

    Article  CAS  PubMed  Google Scholar 

  • Kompella UB, Kadam RS, Lee VH (2010) Recent advances in ophthalmic drug delivery. Ther Deliv 1(3):435–456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kompella UB, Amrite AC, Pacha Ravi R, Durazo SA (2013) Nanomedicines for back of the eye drug delivery, gene delivery, and imaging. Prog Retin Eye Res 36:172–198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Konat Zorzi G, Contreras-Ruiz L, Parraga JE, Lopez-Garcia A, Romero Bello R, Diebold Y et al (2011) Expression of MUC5AC in ocular surface epithelial cells using cationized gelatin nanoparticles. Mol Pharm 8(5):1783–1788

    Article  CAS  PubMed  Google Scholar 

  • Kuno N, Fujii S (2011) Recent advances in ocular drug delivery systems. Polymers (Basel) 3(1):193–221

    Article  CAS  Google Scholar 

  • Kuwano M, Ibuki H, Morikawa N, Ota A, Kawashima Y (2002) Cyclosporine A formulation affects its ocular distribution in rabbits. Pharm Res 19(1):108–111

    Article  CAS  PubMed  Google Scholar 

  • Lallemand F, Furrer P, Felt-Baeyens O, Gex-Fabry M, Dumont JM, Besseghir K et al (2005) A novel water-soluble cyclosporine A prodrug: ocular tolerance and in vivo kinetics. Int J Pharm 295(1–2):7–14

    Article  CAS  PubMed  Google Scholar 

  • Lallemand F, Varesio E, Felt-Baeyens O, Bossy L, Hopfgartner G, Gurny R (2007) Biological conversion of a water-soluble prodrug of cyclosporine A. Eur J Pharm Biopharm 67(2):555–561

    Article  CAS  PubMed  Google Scholar 

  • Law SL, Huang KJ, Chiang CH (2000) Acyclovir-containing liposomes for potential ocular delivery. Corneal penetration and absorption. J Control Release 63(1–2):135–140

    Article  CAS  PubMed  Google Scholar 

  • Lee VH (1983) Esterase activities in adult rabbit eyes. J Pharm Sci 72(3):239–244

    Article  CAS  PubMed  Google Scholar 

  • Lee VH, Robinson JR (1986) Topical ocular drug delivery: recent developments and future challenges. J Ocul Pharmacol 2(1):67–108

    Article  CAS  PubMed  Google Scholar 

  • Lee JH, Pidaparti RM, Atkinson GM, Moorthy RS (2012) Design of an implantable device for ocular drug delivery. J Drug Deliv 2012:527516

    PubMed  PubMed Central  Google Scholar 

  • Li N, Zhuang C, Wang M, Sun X, Nie S, Pan W (2009) Liposome coated with low molecular weight chitosan and its potential use in ocular drug delivery. Int J Pharm 379(1):131–138

    Article  CAS  PubMed  Google Scholar 

  • Lo R, Li PY, Saati S, Agrawal RN, Humayun MS, Meng E (2009) A passive MEMS drug delivery pump for treatment of ocular diseases. Biomed Microdevices 11(5):959–970

    Article  CAS  PubMed  Google Scholar 

  • Losa C, Calvo P, Castro E, Vila-Jato JL, Alonso MJ (1991) Improvement of ocular penetration of amikacin sulphate by association to poly(butylcyanoacrylate) nanoparticles. J Pharm Pharmacol 43(8):548–552

    Article  CAS  PubMed  Google Scholar 

  • 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(1):80–87

    Article  CAS  PubMed  Google Scholar 

  • Lu C, Yoganathan RB, Kociolek M, Allen C (2013) Hydrogel containing silica shell cross-linked micelles for ocular drug delivery. J Pharm Sci 102(2):627–637

    Article  CAS  PubMed  Google Scholar 

  • Luo Q, Zhao J, Zhang X, Pan W (2011) Nanostructured lipid carrier (NLC) coated with Chitosan Oligosaccharides and its potential use in ocular drug delivery system. Int J Pharm 403(1–2):185–191

    Article  CAS  PubMed  Google Scholar 

  • Mac Gabhann F, Demetriades AM, Deering T, Packer JD, Shah SM, Duh E et al (2007) Protein transport to choroid and retina following periocular injection: theoretical and experimental study. Ann Biomed Eng 35(4):615–630

    Article  PubMed  Google Scholar 

  • Macha S, Mitra AK (2003) Overview of ocular drug delivery. In: Mitra AK (ed) Ophthalmic drug delivery systems, 2nd edn. Marcel Dekker, New York, pp 1–12

    Chapter  Google Scholar 

  • Mainolfi N, Powers J, Amin J, Long D, Lee W, McLaughlin ME et al (2013) An effective prodrug strategy to selectively enhance ocular exposure of a cannabinoid receptor (CB1/2) agonist. J Med Chem 56(13):5464–5472

    Article  CAS  PubMed  Google Scholar 

  • Maiti S, Paul S, Mondol R, Ray S, Sa B (2011) Nanovesicular formulation of brimonidine tartrate for the management of glaucoma: in vitro and in vivo evaluation. AAPS PharmSciTech 12(2):755–763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Majumdar S, Nashed YE, Patel K, Jain R, Itahashi M, Neumann DM et al (2005) Dipeptide monoester ganciclovir prodrugs for treating HSV-1-induced corneal epithelial and stromal keratitis: in vitro and in vivo evaluations. J Ocul Pharmacol Ther 21(6):463–474

    Article  CAS  PubMed  Google Scholar 

  • 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):1136–1163

    Article  CAS  PubMed  Google Scholar 

  • Matsuo T, Masuda I, Yasuda T, Matsuo N (1996) Gene transfer to the retina of rat by liposome eye drops. Biochem Biophys Res Commun 219(3):947–950

    Article  CAS  PubMed  Google Scholar 

  • 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):108–118

    Article  CAS  PubMed  Google Scholar 

  • Mishima S (1981) Clinical pharmacokinetics of the eye. Proctor lecture. Invest Ophthalmol Vis Sci 21(4):504–541

    CAS  PubMed  Google Scholar 

  • Mitra AK, Velagaleti PR, Grau UM (2010) Topical drug delivery systems for ophthalmic use. Google Patents

    Google Scholar 

  • Mohammadi S, Jones L, Gorbet M (2014) Extended latanoprost release from commercial contact lenses: in vitro studies using corneal models. PLoS One 9(9), e106653

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Molokhia SA, Jeong EK, Higuchi WI, Li SK (2008) Examination of barriers and barrier alteration in transscleral iontophoresis. J Pharm Sci 97(2):831–844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Molokhia SA, Jeong EK, Higuchi WI, Li SK (2009) Transscleral iontophoretic and intravitreal delivery of a macromolecule: study of ocular distribution in vivo and postmortem with MRI. Exp Eye Res 88(3):418–425

    Article  CAS  PubMed  Google Scholar 

  • 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. Vision Res 50(7):680–685

    Article  CAS  PubMed  Google Scholar 

  • Molokhia SA, Thomas SC, Garff KJ, Mandell KJ, Wirostko BM (2013) Anterior eye segment drug delivery systems: current treatments and future challenges. J Ocul Pharmacol Ther 29(2):92–105

    Article  CAS  PubMed  Google Scholar 

  • Monem AS, Ali FM, Ismail MW (2000) Prolonged effect of liposomes encapsulating pilocarpine HCl in normal and glaucomatous rabbits. Int J Pharm 198(1):29–38

    Article  CAS  PubMed  Google Scholar 

  • Moosa RM, Choonara YE, du Toit LC, Kumar P, Carmichael T, Tomar LK et al (2014) A review of topically administered mini-tablets for drug delivery to the anterior segment of the eye. J Pharm Pharmacol 66(4):490–506

    Article  CAS  PubMed  Google Scholar 

  • Muchtar S, Almog S, Torracca MT, Saettone MF, Benita S (1992) A submicron emulsion as ocular vehicle for delta-8-tetrahydrocannabinol: effect on intraocular pressure in rabbits. Ophthalmic Res 24(3):142–149

    Article  CAS  PubMed  Google Scholar 

  • Nagarsenker MS, Londhe VY, Nadkarni GD (1999) Preparation and evaluation of liposomal formulations of tropicamide for ocular delivery. Int J Pharm 190(1):63–71

    Article  CAS  PubMed  Google Scholar 

  • Nair KL, Vidyanand S, James J, Kumar GSV (2012) Pilocarpine-loaded poly(DLlactic-co-glycolic acid) nanoparticles as potential candidates for controlled drug delivery with enhanced ocular pharmacological response. J Appl Polym Sci 124:2030–2036

    Article  CAS  Google Scholar 

  • NeurotechUSA. Available from: http://www.neurotechusa.com/cntfrenexus.html

  • Nicoli S, Ferrari G, Quarta M, Macaluso C, Santi P (2009) In vitro transscleral iontophoresis of high molecular weight neutral compounds. Eur J Pharm Sci 36(4–5):486–492

    Article  CAS  PubMed  Google Scholar 

  • Normand N, Valamanesh F, Savoldelli M, Mascarelli F, BenEzra D, Courtois Y et al (2005) VP22 light controlled delivery of oligonucleotides to ocular cells in vitro and in vivo. Mol Vis 11(21):184–191

    CAS  PubMed  Google Scholar 

  • Olsen TW, Aaberg SY, Geroski DH, Edelhauser HF (1998) Human sclera: thickness and surface area. Am J Ophthalmol 125(2):237–241

    Article  CAS  PubMed  Google Scholar 

  • Paasonen L, Laaksonen T, Johans C, Yliperttula M, Kontturi K, Urth A (2007) Gold nanoparticles enable selective light-induced contents release from liposomes. J Control Release 122(1):86–93

    Article  CAS  PubMed  Google Scholar 

  • Parkinson TM, Ferguson E, Febbraro S, Bakhtyari A, King M, Mundasad M (2003) Tolerance of ocular iontophoresis in healthy volunteers. J Ocul Pharmacol Ther 19(2):145–151

    Article  CAS  PubMed  Google Scholar 

  • Pascolini D, Mariotti SP (2012) Global estimates of visual impairment: 2010. Br J Ophthalmol 96(5):614–618

    Article  PubMed  Google Scholar 

  • Patel SR, Berezovsky DE, McCarey BE, Zarnitsyn V, Edelhauser HF, Prausnitz MR (2012) Targeted administration into the suprachoroidal space using a microneedle for drug delivery to the posterior segment of the eye. Invest Ophthalmol Vis Sci 53(8):4433–4441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pearce W, Hsu J, Yeh S (2015) Advances in drug delivery to the posterior segment. Curr Opin Ophthalmol 26(3):233–239

    Article  PubMed  PubMed Central  Google Scholar 

  • Pederson J (2006) Fluid physiology of the subretinal space. In: Rayan SJ (ed) Retina, 4th edn. Elsevier Inc., Philadelphia, pp 1909–1920

    Chapter  Google Scholar 

  • Pehlivan SB, Yavuz B, Calamak S, Ulubayram K, Kaffashi A, Vural I et al (2015) Preparation and in vitro/in vivo evaluation of cyclosporin A-loaded nanodecorated ocular implants for subconjunctival application. J Pharm Sci 104(5):1709–1720

    Article  CAS  PubMed  Google Scholar 

  • Peng CC, Burke MT, Carbia BE, Plummer C, Chauhan A (2012) Extended drug delivery by contact lenses for glaucoma therapy. J Control Release 162(1):152–158

    Article  CAS  PubMed  Google Scholar 

  • Pepic I, Jalsenjak N, Jalsenjak I (2004) Micellar solutions of triblock copolymer surfactants with pilocarpine. Int J Pharm 272(1–2):57–64

    Article  CAS  PubMed  Google Scholar 

  • Pepic I, Hafner A, Lovric J, Pirkic B, Filipovic-Grcic J (2010) A nonionic surfactant/chitosan micelle system in an innovative eye drop formulation. J Pharm Sci 99(10):4317–4325

    Article  CAS  PubMed  Google Scholar 

  • Peyman GA, Schulman JA, Khoobehi B, Alkan HM, Tawakol ME, Mani H (1989) Toxicity and clearance of a combination of liposome-encapsulated ganciclovir and trifluridine. Retina 9(3):232–236

    Article  CAS  PubMed  Google Scholar 

  • Phan CM, Subbaraman L, Jones L (2014) Contact lenses for antifungal ocular drug delivery: a review. Expert Opin Drug Deliv 11(4):537–546

    Article  CAS  PubMed  Google Scholar 

  • 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):53–61

    Article  CAS  PubMed  Google Scholar 

  • Prabhu P, Nitish KR, Koland M, Harish N, Vijayanarayan K, Dhondge G et al (2010) Preparation and evaluation of nano-vesicles of brimonidine tartrate as an ocular drug delivery system. J Young Pharm 2(4):356–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quintana-Hau JD, Cruz-Olmos E, Lopez-Sanchez MI, Sanchez-Castellanos V, Baiza-Duran L, Gonzalez JR et al (2005) Characterization of the novel ophthalmic drug carrier Sophisen in two of its derivatives: 3A Ofteno and Modusik-A Ofteno. Drug Dev Ind Pharm 31(3):263–269

    Article  CAS  PubMed  Google Scholar 

  • Rafie F, Javadzadeh Y, Javadzadeh AR, Ghavidel LA, Jafari B, Moogooee M et al (2010) In vivo evaluation of novel nanoparticles containing dexamethasone for ocular drug delivery on rabbit eye. Curr Eye Res 35(12):1081–1089

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Ranta VP, Mannermaa E, Lummepuro K, Subrizi A, Laukkanen A, Antopolsky M et al (2010) Barrier analysis of periocular drug delivery to the posterior segment. J Control Release 148(1):42–48

    Article  CAS  PubMed  Google Scholar 

  • Reimondez-Troitino S, Csaba N, Alonso MJ, de la Fuente M (2015) Nanotherapies for the treatment of ocular diseases. Eur J Pharm Biopharm 95(Pt B):279–293

    Google Scholar 

  • Reimondez-Troitino S, Csaba N, Alonso MJ, de la Fuente M (2015b) Nanotherapies for the treatment of ocular diseases. Eur J Pharm Biopharm 95:279–293

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez-Aller M, Kaufmann B, Guillarme D, Stella C, Furrer P, Rudaz S et al (2012) In vivo characterisation of a novel water-soluble cyclosporine A prodrug for the treatment of dry eye disease. Eur J Pharm Biopharm 80(3):544–552

    Article  CAS  PubMed  Google Scholar 

  • Rowe-Rendleman CL, Durazo SA, Kompella UB, Rittenhouse KD, Di Polo A, Weiner AL et al (2014) Drug and gene delivery to the back of the eye: from bench to bedside. Invest Ophthalmol Vis Sci 55(4):2714–2730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruponen M, Urtti A (2015) Undefined role of mucus as a barrier in ocular drug delivery. Eur J Pharm Biopharm 96:442–446

    Article  CAS  PubMed  Google Scholar 

  • Saati S, Lo R, Li PY, Meng E, Varma R, Humayun MS (2010) Mini drug pump for ophthalmic use. Curr Eye Res 35(3):192–201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sachinkumar P, Atul K, Sandip B, Shitalkumar P (2015) Formuation and evaluation of an in situ gel for ocular drug delivery of anticonjunctival drug. Cellul Chem Technol 49(1):35–40

    Google Scholar 

  • Saha P, Yang JJ, Lee VH (1998) Existence of a p-glycoprotein drug efflux pump in cultured rabbit conjunctival epithelial cells. Invest Ophthalmol Vis Sci 39(7):1221–1226

    CAS  PubMed  Google Scholar 

  • Sanders DR, Goldstick B, Kraff C, Hutchins R, Bernstein MS, Evans MA (1983) Aqueous penetration of oral and topical indomethacin in humans. Arch Ophthalmol 101(10):1614–1616

    Article  CAS  PubMed  Google Scholar 

  • Santipharp P, Laman LA (2008) Ophthalmic nanoparticulate formulation of a cyclooxygenase-2 selective inhibitor. Patent US20080145430 A1

    Google Scholar 

  • Schoenwald RD (1990) Ocular drug delivery. Pharmacokinetic considerations. Clin Pharmacokinet 18(4):255–269

    Article  CAS  PubMed  Google Scholar 

  • Sedlacek J (1965) Possibility of the application of ophthalmic drugs with the use of gel contact lenses. Cesk Oftalmol 21(6):509–512

    CAS  PubMed  Google Scholar 

  • Shell JW (1985) Ophthalmic drug delivery systems. Drug Dev Res 6(3):245–261

    Article  CAS  Google Scholar 

  • Shen Y, Tu J (2007) Preparation and ocular pharmacokinetics of ganciclovir liposomes. AAPS J 9(3):E371–E377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen J, Deng Y, Jin X, Ping Q, Su Z, Li L (2010) Thiolated nanostructured lipid carriers as a potential ocular drug delivery system for cyclosporine A: improving in vivo ocular distribution. Int J Pharm 402(1–2):248–253

    Article  CAS  PubMed  Google Scholar 

  • Shen J, Gan L, Zhu C, Zhang X, Dong Y, Jiang M et al (2011) Novel NSAIDs ophthalmic formulation: flurbiprofen axetil emulsion with low irritancy and improved anti-inflammation effect. Int J Pharm 412(1-2):115–122

    Article  CAS  PubMed  Google Scholar 

  • Shukla A, Fuller RC, Hammond PT (2011) Design of multi-drug release coatings targeting infection and inflammation. J Control Release 155(2):159–166

    Article  CAS  PubMed  Google Scholar 

  • Sigurdsson HH, Kirch J, Lehr CM (2013) Mucus as a barrier to lipophilic drugs. Int J Pharm 453(1):56–64

    Article  CAS  PubMed  Google Scholar 

  • Sjoquist B, Stjernschantz J (2002) Ocular and systemic pharmacokinetics of latanoprost in humans. Surv Ophthalmol 47(Suppl 1):S6–S12

    Article  PubMed  Google Scholar 

  • Spataro G, Malecaze F, Turrin CO, Soler V, Duhayon C, Elena PP et al (2010) Designing dendrimers for ocular drug delivery. Eur J Med Chem 45(1):326–334

    Article  CAS  PubMed  Google Scholar 

  • Spraul CW, Lang GE, Grossniklaus HE, Lang GK (1999) Histologic and morphometric analysis of the choroid, Bruch’s membrane, and retinal pigment epithelium in postmortem eyes with age-related macular degeneration and histologic examination of surgically excised choroidal neovascular membranes. Surv Ophthalmol 44(Suppl 1):S10–S32

    Article  PubMed  Google Scholar 

  • Steuer H, Jaworski A, Elger B, Kaussmann M, Keldenich J, Schneider H et al (2005) Functional characterization and comparison of the outer blood-retina barrier and the blood-brain barrier. Invest Ophthalmol Vis Sci 46(3):1047–1053

    Article  PubMed  Google Scholar 

  • Stratford RE Jr, Lee VH (1985) Ocular aminopeptidase activity and distribution in the albino rabbit. Curr Eye Res 4(9):995–999

    Article  CAS  PubMed  Google Scholar 

  • Sznitowska M, Zurowska-Pryczkowska K, Janicki S, Jarvinen T (1999) Miotic effect and irritation potential of pilocarpine prodrug incorporated into a submicron emulsion vehicle. Int J Pharm 184(1):115–120

    Article  CAS  PubMed  Google Scholar 

  • Taban M, Chen B, Perry JD (2006) Update on punctal plugs. Compr Ophthalmol Updat 7(5):205–212, discussion 213–214

    Google Scholar 

  • Talluri RS, Katragadda S, Pal D, Mitra AK (2006) Mechanism of L-ascorbic acid uptake by rabbit corneal epithelial cells: evidence for the involvement of sodium-dependent vitamin C transporter 2. Curr Eye Res 31(6):481–489

    Article  CAS  PubMed  Google Scholar 

  • Thrimawithana TR, Young S, Bunt CR, Green C, Alany RG (2011) Drug delivery to the posterior segment of the eye. Drug Discov Today 16(5-6):270–277

    Article  CAS  PubMed  Google Scholar 

  • Ticho U, Blumenthal M, Zonis S, Gal A, Blank I, Mazor ZW (1979) A clinical trial with Piloplex--a new long-acting pilocarpine compound: preliminary report. Ann Ophthalmol 11(4):555–561

    CAS  PubMed  Google Scholar 

  • Tirucherai GS, Dias C, Mitra AK (2002) Corneal permeation of ganciclovir: mechanism of ganciclovir permeation enhancement by acyl ester prodrug design. J Ocul Pharmacol Ther 18(6):535–548

    Article  CAS  PubMed  Google Scholar 

  • Tong YC, Chang SF, Liu CY, Kao WW, Huang CH, Liaw J (2007) Eye drop delivery of nano-polymeric micelle formulated genes with cornea-specific promoters. J Gene Med 9(11):956–966

    Article  CAS  PubMed  Google Scholar 

  • Trivedi R, Kompella UB (2010) Nanomicellar formulations for sustained drug delivery: strategies and underlying principles. Nanomedicine (Lond) 5(3):485–505

    Article  CAS  Google Scholar 

  • Trivedi R, Redente EF, Thakur A, Riches DW, Kompella UB (2012) Local delivery of biodegradable pirfenidone nanoparticles ameliorates bleomycin-induced pulmonary fibrosis in mice. Nanotechnology 23(50):505101

    Article  PubMed  CAS  Google Scholar 

  • Tyagi P, Barros M, Stansbury JW, Kompella UB (2013) Light-activated, in situ forming gel for sustained suprachoroidal delivery of bevacizumab. Mol Pharm 10(8):2858–2867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vadlapudi AD, Vadlapatla RK, Kwatra D, Earla R, Samanta SK, Pal D et al (2012a) Targeted lipid based drug conjugates: a novel strategy for drug delivery. Int J Pharm 434(1-2):315–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vadlapudi AD, Vadlapatla RK, Mitra AK (2012b) Current and emerging antivirals for the treatment of cytomegalovirus (CMV) retinitis: an update on recent patents. Recent Pat Antiinfect Drug Discov 7(1):8–18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vadlapudi AD, Cholkar K, Vadlapatla RK, Mitra AK (2014) Aqueous nanomicellar formulation for topical delivery of biotinylated lipid prodrug of acyclovir: formulation development and ocular biocompatibility. J Ocul Pharmacol Ther 30(1):49–58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valls R, Vega E, Garcia ML, Egea MA, Valls JO (2008) Transcorneal permeation in a corneal device of non-steroidal anti-inflammatory drugs in drug delivery systems. Open Med Chem J 2:66–71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vandamme TF, Brobeck L (2005) Poly(amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide. J Control Release 102(1):23–38

    Article  CAS  PubMed  Google Scholar 

  • Vega E, Egea MA, Valls O, Espina M, Garcia ML (2006) Flurbiprofen loaded biodegradable nanoparticles for ophthalmic administration. J Pharm Sci 95(11):2393–2405

    Article  CAS  PubMed  Google Scholar 

  • Vinogradov SV, Batrakova EV, Kabanov AV (2004) Nanogels for oligonucleotide delivery to the brain. Bioconjug Chem 15(1):50–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vooturi SK, Kadam RS, Kompella UB (2012) Transporter targeted gatifloxacin prodrugs: synthesis, permeability, and topical ocular delivery. Mol Pharm 9(11):3136–3146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Wong VG (1989) Biodegradable ocular implants. Google Patents

    Google Scholar 

  • Wu J, Zhang JJ, Koppel H, Jacob TJ (1996) P-glycoprotein regulates a volume-activated chloride current in bovine non-pigmented ciliary epithelial cells. J Physiol 491(Pt 3):743–755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiang CD, Batugo M, Gale DC, Zhang T, Ye J, Li C et al (2009) Characterization of human corneal epithelial cell model as a surrogate for corneal permeability assessment: metabolism and transport. Drug Metab Dispos 37(5):992–998

    Article  CAS  PubMed  Google Scholar 

  • Xu X, Weng YH, Xu L, Chen H (2013) Sustained release of avastin (R) from polysaccharides cross-linked hydrogels for ocular drug delivery. Int J Biol Macromol 60:272–276

    Article  CAS  PubMed  Google Scholar 

  • Yavuz B, Pehlivan SB, Vural I, Unlu N (2015) In vitro/in vivo evaluation of Dexamethasone--PAMAM dendrimer complexes for retinal drug delivery. J Pharm Sci 104(11):3814–3823

    Article  CAS  PubMed  Google Scholar 

  • Yellepeddi VK, Sheshala R, McMillan H, Gujral C, Jones D, Raghu Raj Singh T (2015) Punctal plug: a medical device to treat dry eye syndrome and for sustained drug delivery to the eye. Drug Discov Today 20(7):884–889

    Article  CAS  PubMed  Google Scholar 

  • Yenice I, Mocan MC, Palaska E, Bochot A, Bilensoy E, Vural I et al (2008) Hyaluronic acid coated poly-epsilon-caprolactone nanospheres deliver high concentrations of cyclosporine A into the cornea. Exp Eye Res 87(3):162–167

    Article  CAS  PubMed  Google Scholar 

  • Yu J, Xu X, Yao FL, Luo ZC, Jin L, Xie BB et al (2014) In situ covalently cross-linked PEG hydrogel for ocular drug delivery applications. Int J Pharm 470(1–2):151–157

    Article  CAS  PubMed  Google Scholar 

  • Yuan XB, Yuan YB, Jiang W, Liu J, Tian EJ, Shun HM et al (2008) Preparation of rapamycin-loaded chitosan/PLA nanoparticles for immunosuppression in corneal transplantation. Int J Pharm 349(1–2):241–248

    Article  CAS  PubMed  Google Scholar 

  • Zhang T, Xiang CD, Gale D, Carreiro S, Wu EY, Zhang EY (2008) Drug transporter and cytochrome P450 mRNA expression in human ocular barriers: implications for ocular drug disposition. Drug Metab Dispos 36(7):1300–1307

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This was supported in part by the NIH grants EY022097, EY024072, and EY018940 and the US FDA grants FD004929 and FD004719. The authors are thankful to Dr. Ryan A. Kelley for his editorial assistance and review of this chapter.

Author information

Authors and Affiliations

  1. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, 12850 East Montview Blvd., C238-V20, Aurora, CO, 80045, USA

    Burcin Yavuz & Uday B. Kompella

  2. Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA

    Burcin Yavuz

Authors
  1. Burcin Yavuz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Uday B. Kompella
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Uday B. Kompella .

Editor information

Editors and Affiliations

  1. Akrivista and Whitecap Biosciences, Mission Viejo, California, USA

    Scott M. Whitcup

  2. Illinois Eye and Ear Infirmary, University of Illinois at Chicago College of Medicine, Chicago, Illinois, USA

    Dimitri T. Azar

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Yavuz, B., Kompella, U.B. (2016). Ocular Drug Delivery. In: Whitcup, S., Azar, D. (eds) Pharmacologic Therapy of Ocular Disease. Handbook of Experimental Pharmacology, vol 242. Springer, Cham. https://doi.org/10.1007/164_2016_84

Download citation

Publish with us

Policies and ethics

Search

Navigation