Breaking Barriers in Eye Treatment: Polymeric Nano-Based Drug-Delivery System for Anterior Segment Diseases and Glaucoma

The eye has anatomical structures that function as robust static and dynamic barriers, limiting the penetration, residence time, and bioavailability of medications administered topically. The development of polymeric nano-based drug-delivery systems (DDS) could be the solution to these challenges: it can pass through ocular barriers, offering higher bioavailability of administered drugs to targeted tissues that are otherwise inaccessible; it can stay in ocular tissues for longer periods of time, requiring fewer drug administrations; and it can be made up of polymers that are biodegradable and nano-sized, minimizing the undesirable effects of the administered molecules. Therefore, therapeutic innovations in polymeric nano-based DDS have been widely explored for ophthalmic drug-delivery applications. In this review, we will give a comprehensive overview of polymeric nano-based drug-delivery systems (DDS) used in the treatment of ocular diseases. We will then examine the current therapeutic challenges of various ocular diseases and analyze how different types of biopolymers can potentially enhance our therapeutic options. A literature review of the preclinical and clinical studies published between 2017 and 2022 was conducted. Thanks to the advances in polymer science, the ocular DDS has rapidly evolved, showing great promise to help clinicians better manage patients.

[1]  Guihua Fang,et al.  Cyclodextrin-based ocular drug delivery systems: A comprehensive review , 2023, Coordination Chemistry Reviews.

[2]  J. E. Lee,et al.  Clinical efficacy of 0.05% cyclosporine nano-emulsion in the treatment of dry eye syndrome associated with meibomian gland dysfunction. , 2022, International journal of ophthalmology.

[3]  F. Medeiros,et al.  Bimatoprost Implant Biodegradation in the Phase 3, Randomized, 20-Month ARTEMIS Studies , 2022, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[4]  W. Pan,et al.  Optimization and Characterization of Low-Molecular-Weight Chitosan-Coated Baicalin mPEG-PLGA Nanoparticles for the Treatment of Cataract. , 2022, Molecular pharmaceutics.

[5]  J. Sun,et al.  Rebamipide liposome as an effective ocular delivery system for the management of dry eye disease , 2022, Journal of Drug Delivery Science and Technology.

[6]  H. Yang,et al.  Dendrimer-based drug delivery systems: history, challenges, and latest developments , 2022, Journal of Biological Engineering.

[7]  Xi Lin,et al.  Nanoparticles in ocular applications and their potential toxicity , 2022, Frontiers in Molecular Biosciences.

[8]  M. Foldvari,et al.  Peptide-Modified Gemini Surfactants as Delivery System Building Blocks with Dual Functionalities for Glaucoma Treatment: Gene Carriers and Amyloid-Beta (Aβ) Self-Aggregation Inhibitors. , 2022, Molecular pharmaceutics.

[9]  Yanzhang Liu,et al.  Fabrication of Anti-Oxidant Curcumin loaded Ceria Nanoclusters for the novel Delivery system to Prevention of Selenite-Induced Cataract Therapy in Alleviating Diabetic Cataract , 2022, Process Biochemistry.

[10]  Jingtian Han,et al.  N-acetylcysteine functionalized chitosan oligosaccharide-palmitic acid conjugate enhances ophthalmic delivery of flurbiprofen and its mechanisms. , 2022, Carbohydrate polymers.

[11]  Deng-Guang Yu,et al.  Recent Advances in Poly(α-L-glutamic acid)-Based Nanomaterials for Drug Delivery , 2022, Biomolecules.

[12]  L. Rajagopalan,et al.  Intraocular Pressure-Lowering Efficacy of a Sustained-Release Bimatoprost Implant in Dog Eyes Pretreated with Selective Laser Trabeculoplasty , 2022, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[13]  L. Gonçalves,et al.  Chitosan and Hyaluronic Acid Nanoparticles as Vehicles of Epoetin Beta for Subconjunctival Ocular Delivery , 2022, Marine drugs.

[14]  L. Spirikhin,et al.  Hydrogels on the Base of Modified Chitosan and Hyaluronic Acid Mix as Polymer Matrices for Cytostatics Delivery , 2022, Gels.

[15]  I. Bravo-Osuna,et al.  Validation of a Rapid and Easy-to-Apply Method to Simultaneously Quantify Co-Loaded Dexamethasone and Melatonin PLGA Microspheres by HPLC-UV: Encapsulation Efficiency and In Vitro Release , 2022, Pharmaceutics.

[16]  X. Loh,et al.  Effectiveness of an ocular adhesive polyhedral oligomeric silsesquioxane hybrid thermo-responsive FK506 hydrogel in a murine model of dry eye , 2021, Bioactive materials.

[17]  C. Alvarez‐Lorenzo,et al.  Injectable Depot Forming Thermoresponsive Hydrogel for Sustained Intrascleral Delivery of Sunitinib Using Hollow Microneedles. , 2022, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[18]  K. Swindle-Reilly,et al.  Considerations for Polymers Used in Ocular Drug Delivery , 2022, Frontiers in Medicine.

[19]  D. Tzetzis,et al.  In Situ Gelling Electrospun Ocular Films Sustain the Intraocular Pressure-Lowering Effect of Timolol Maleate: In Vitro, Ex Vivo, and Pharmacodynamic Assessment. , 2021, Molecular pharmaceutics.

[20]  Abdelwahab Omri,et al.  Cellulosic Polymers for Enhancing Drug Bioavailability in Ocular Drug Delivery Systems , 2021, Pharmaceuticals.

[21]  H. McCarthy,et al.  Dissolving microneedle patches loaded with amphotericin B microparticles for localised and sustained intradermal delivery: Potential for enhanced treatment of cutaneous fungal infections. , 2021, Journal of controlled release : official journal of the Controlled Release Society.

[22]  Yin Zhao,et al.  Polydopamine nanoparticles attenuate retina ganglion cell degeneration and restore visual function after optic nerve injury , 2021, Journal of Nanobiotechnology.

[23]  S. Saber-Samandari,et al.  Alginate nanoparticles as ocular drug delivery carriers , 2021, Journal of Drug Delivery Science and Technology.

[24]  Y. Lei,et al.  Endogenous dual stimuli-activated NO generation in the conventional outflow pathway for precision glaucoma therapy. , 2021, Biomaterials.

[25]  M. Ansari,et al.  Formulation of carteolol chitosomes for ocular delivery: formulation optimization, ex-vivo permeation, and ocular toxicity examination , 2021, Cutaneous and ocular toxicology.

[26]  J. Loscalzo,et al.  Retinal Protection by Sustained Nanoparticle Delivery of Oncostatin M and Ciliary Neurotrophic Factor Into Rodent Models of Retinal Degeneration , 2021, Translational vision science & technology.

[27]  Yang Xu,et al.  Hyaluronic acid in ocular drug delivery. , 2021, Carbohydrate polymers.

[28]  K. Kesavan,et al.  Phase Transition Microemulsion of Brimonidine Tartrate for Glaucoma Therapy: Preparation, Characterization and Pharmacodynamic Study , 2021, Current eye research.

[29]  H. Sheardown,et al.  Ocular drug delivery to the anterior segment using nanocarriers: A mucoadhesive/mucopenetrative perspective. , 2021, Journal of controlled release : official journal of the Controlled Release Society.

[30]  A. Nokhodchi,et al.  Polyvinyl Alcohol/Chitosan Single-Layered and Polyvinyl Alcohol/Chitosan/Eudragit RL100 Multi-layered Electrospun Nanofibers as an Ocular Matrix for the Controlled Release of Ofloxacin: an In Vitro and In Vivo Evaluation , 2021, AAPS PharmSciTech.

[31]  R. Herrero-Vanrell,et al.  The Effect of a Triple Combination of Bevacizumab, Sodium Hyaluronate and a Collagen Matrix Implant in a Trabeculectomy Animal Model , 2021, Pharmaceutics.

[32]  Nasiru Wo,et al.  Combinatorial therapeutic drug delivery of riboflavin and dexamethasone for the treatment of keratoconus affected corneas of mice: Ex vivo permeation and hemolytic toxicity , 2021, Micro & Nano Letters.

[33]  H. Gong,et al.  Surface Engineering of FLT4-Targeted Nanocarriers Enhances Cell-Softening Glaucoma Therapy , 2021, bioRxiv.

[34]  Preeya K Gupta,et al.  The role of KPI-121 0.25% in the treatment of dry eye disease: penetrating the mucus barrier to treat periodic flares , 2021, Therapeutic advances in ophthalmology.

[35]  D. Zack,et al.  Ion-Complex Microcrystal Formulation Provides Sustained Delivery of a Multimodal Kinase Inhibitor from the Subconjunctival Space for Protection of Retinal Ganglion Cells , 2021, Pharmaceutics.

[36]  Xinghuai Sun,et al.  A miRNA stabilizing polydopamine nano-platform for intraocular delivery of miR-21-5p in glaucoma therapy. , 2021, Journal of materials chemistry. B.

[37]  P. Sharma,et al.  Optimization and Characterization of Brimonidine Tartrate Nanoparticles-loaded In Situ Gel for the Treatment of Glaucoma , 2021, Current eye research.

[38]  S. Benita,et al.  Topical tacrolimus νanocapsules eye drops for therapeutic effect enhancement in both anterior and posterior ocular inflammation models. , 2021, Journal of controlled release : official journal of the Controlled Release Society.

[39]  A. Urtti,et al.  Intravitreal Polymeric Nanocarriers with Long Ocular Retention and Targeted Delivery to the Retina and Optic Nerve Head Region , 2021, Pharmaceutics.

[40]  B. Bui,et al.  Targeted Delivery of LM22A-4 by Cubosomes Protects Retinal Ganglion Cells in An Experimental Glaucoma Model. , 2021, Acta biomaterialia.

[41]  Shi-you Zhou,et al.  Efficacy, Safety, and Tolerability of a Novel Cyclosporine, a Formulation for Dry Eye Disease: A Multicenter Phase II Clinical Study. , 2021, Clinical therapeutics.

[42]  Xiaobo Mao,et al.  Role of Retinal Amyloid-β in Neurodegenerative Diseases: Overlapping Mechanisms and Emerging Clinical Applications , 2021, International journal of molecular sciences.

[43]  K. S. Prasad,et al.  Why chitosan could be apt candidate for glaucoma drug delivery - An overview. , 2021, International journal of biological macromolecules.

[44]  P. Coimbra,et al.  Comparative Analysis of Morphological and Release Profiles in Ocular Implants of Acetazolamide Prepared by Electrospinning , 2021, Pharmaceutics.

[45]  D. Petri,et al.  Hydroxypropyl methylcellulose: physicochemical properties and ocular drug delivery formulations. , 2021, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[46]  P. Venkatesh,et al.  Comparative evaluation of once-daily and twice-daily dosing of topical bromfenac 0.09%: aqueous pharmacokinetics and clinical efficacy study , 2021, Journal of cataract and refractive surgery.

[47]  K. Nguyen,et al.  Nanoencapsulated hybrid compound SA-2 with long-lasting intraocular pressure–lowering activity in rodent eyes , 2021, Molecular vision.

[48]  T. Wong,et al.  Positive-charge tuned gelatin hydrogel-siSPARC injectable for siRNA anti-scarring therapy in post glaucoma filtration surgery , 2021, Scientific Reports.

[49]  F. Otero-Espinar,et al.  Design, Optimization, and Characterization of Lactoferrin-Loaded Chitosan/TPP and Chitosan/Sulfobutylether-β-cyclodextrin Nanoparticles as a Pharmacological Alternative for Keratoconus Treatment. , 2021, ACS applied materials & interfaces.

[50]  Islam A Khalil,et al.  Novel cubosome based system for ocular delivery of acetazolamide , 2021, Drug delivery.

[51]  Q. Ping,et al.  Wettability and contact angle affect precorneal retention and pharmacodynamic behavior of microspheres , 2021, Drug delivery.

[52]  Kexin Sun,et al.  Preparation and Characterization of Tacrolimus-Loaded SLNs in situ Gel for Ocular Drug Delivery for the Treatment of Immune Conjunctivitis , 2021, Drug design, development and therapy.

[53]  C. R. Ethier,et al.  Drug‐Free, Nonsurgical Reduction of Intraocular Pressure for Four Months after Suprachoroidal Injection of Hyaluronic Acid Hydrogel , 2020, Advanced science.

[54]  Jangwook P. Jung,et al.  Stability and ocular biodistribution of topically administered PLGA nanoparticles , 2020, Scientific Reports.

[55]  Yimeng Du,et al.  Size, shape, charge and “stealthy” surface: Carrier properties affect the drug circulation time in vivo , 2020, Asian journal of pharmaceutical sciences.

[56]  A. Al-Nima,et al.  Nanoemulsions as Ophthalmic Drug Delivery Systems , 2020, Turkish journal of pharmaceutical sciences.

[57]  A. Ferreira,et al.  Topical Bimatoprost Insert for Primary Open-Angle Glaucoma and Ocular Hypertension Treatment - A Phase II Controlled Study. , 2020, Current drug delivery.

[58]  Menglong Wang,et al.  Efficient Synthesis of Folate-Conjugated Hollow Polymeric Capsules for Accurate Drug Delivery to Cancer Cells. , 2020, Biomacromolecules.

[59]  E. Stefánsson,et al.  Angiotensin Receptor Blockers in cyclodextrin nanoparticle eye drops: Ocular pharmacokinetics and pharmacologic effect on intraocular pressure , 2020, Acta ophthalmologica.

[60]  J. M. Marchetti,et al.  The use of TPGS in drug delivery systems to overcome biological barriers , 2020 .

[61]  G. M. Gelfuso,et al.  Besifloxacin liposomes with positively charged additives for an improved topical ocular delivery , 2020, Scientific Reports.

[62]  Ge Jiang,et al.  PLGA Nanoparticle Platform for Trans-Ocular Barrier to Enhance Drug Delivery: A Comparative Study Based on the Application of Oligosaccharides in the Outer Membrane of Carriers , 2020, International journal of nanomedicine.

[63]  Ziping Zhang,et al.  Brinzolamide loaded core-shell nanoparticles for enhanced coronial penetration in the treatment of glaucoma , 2020, Journal of applied biomaterials & functional materials.

[64]  Xinghuai Sun,et al.  Prolonged use of nitric oxide donor sodium nitroprusside induces ocular hypertension in mice. , 2020, Experimental eye research.

[65]  Yubin Huang,et al.  Reduction-responsive disulfide linkage core-cross-linked polymeric micelles for site-specific drug delivery , 2020 .

[66]  D. D. Nguyen,et al.  Long-acting mucoadhesive thermogels for improving topical treatments of dry eye disease. , 2020, Materials science & engineering. C, Materials for biological applications.

[67]  A. Kabanov,et al.  Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval. , 2020, Advanced drug delivery reviews.

[68]  J. Mayoral,et al.  Brimonidine-LAPONITE® intravitreal formulation has an ocular hypotensive and neuroprotective effect throughout 6 months of follow-up in a glaucoma animal model. , 2020, Biomaterials science.

[69]  A. Piras,et al.  Quaternary Ammonium Chitosans: The Importance of the Positive Fixed Charge of the Drug Delivery Systems , 2020, International journal of molecular sciences.

[70]  S. Afifi,et al.  "CROWN ETHER NANOVESICLES (CROWNSOMES) REPOSITIONED PHENYTOIN FOR HEALING OF CORNEAL ULCERS". , 2020, Molecular pharmaceutics.

[71]  K. Nichols,et al.  Safety of KPI-121 Ophthalmic Suspension 0.25% in Patients With Dry Eye Disease: A Pooled Analysis of 4 Multicenter, Randomized, Vehicle-Controlled Studies. , 2020, Cornea.

[72]  R. Osman,et al.  Polypeptide and glycosaminoglycan polysaccharide as stabilizing polymers in nanocrystals for a safe ocular hypotensive effect. , 2020, International journal of biological macromolecules.

[73]  Pradeep Kumar,et al.  Thiolation of Biopolymers for Developing Drug Delivery Systems with Enhanced Mechanical and Mucoadhesive Properties: A Review , 2020, Polymers.

[74]  D. Khang,et al.  Potential Therapeutic Usage of Nanomedicine for Glaucoma Treatment , 2020, International journal of nanomedicine.

[75]  Chun Gwon Park,et al.  Brimonidine-montmorillonite hybrid formulation for topical drug delivery to the eye. , 2020, Journal of materials chemistry. B.

[76]  A. Dhar,et al.  A brief review on solid lipid nanoparticles: part and parcel of contemporary drug delivery systems , 2020, RSC advances.

[77]  M. Lazaridou,et al.  Chitosan and its Derivatives for Ocular Delivery Formulations: Recent Advances and Developments , 2020, Polymers.

[78]  D. Shah,et al.  Multiple drug delivery from the drug-implants-laden silicone contact lens: Addressing the issue of burst drug release. , 2020, Materials science & engineering. C, Materials for biological applications.

[79]  Mujtaba A. Qazi,et al.  Phase 3, Randomized, 20-Month Study of Bimatoprost Implant in Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 1). , 2020, Ophthalmology.

[80]  David S. Williams,et al.  Exploring the Impact of Morphology on the Properties of Biodegradable Nanoparticles and Their Diffusion in Complex Biological Medium , 2020, Biomacromolecules.

[81]  A. Ferreira,et al.  New antiglaucomatous agent for the treatment of open angle glaucoma: polymeric inserts for drug release and in vitro and in vivo study. , 2020, Journal of biomedical materials research. Part A.

[82]  S. Mutalik,et al.  Neuroprotection: A versatile approach to combat glaucoma. , 2020, European journal of pharmacology.

[83]  M. Shirley Bimatoprost Implant: First Approval , 2020, Drugs & Aging.

[84]  I. Vural,et al.  Design of ocular drug delivery platforms and in vitro - in vivo evaluation of riboflavin to the cornea by non-interventional (epi-on) technique for keratoconus treatment. , 2020, Journal of controlled release : official journal of the Controlled Release Society.

[85]  O. Sammour,et al.  Nanoemulsion as a feasible and biocompatible carrier for ocular delivery of travoprost: improved pharmacokinetic/pharmacodynamic properties. , 2020, International journal of pharmaceutics.

[86]  H. Yang,et al.  Drug-loaded chitosan film prepared via facile solution casting and air-drying of plain water-based chitosan solution for ocular drug delivery , 2020, Bioactive materials.

[87]  D. Monti,et al.  Development and Characterization of a Novel Peptide-Loaded Antimicrobial Ocular Insert , 2020, Biomolecules.

[88]  G. M. Soliman,et al.  Latanoprost niosomes as a sustained release ocular delivery system for the management of glaucoma , 2020, Drug development and industrial pharmacy.

[89]  Pierre P. D. Kondiah,et al.  Hydrogel Biomaterials for Application in Ocular Drug Delivery , 2020, Frontiers in Bioengineering and Biotechnology.

[90]  S. Jafari,et al.  A Review on Surface-Functionalized Cellulosic Nanostructures as Biocompatible Antibacterial Materials , 2020, Nano-micro letters.

[91]  J. Nepp,et al.  Management of moderate-to-severe dry eye disease using chitosan-N-acetylcysteine (Lacrimera®) eye drops: a retrospective case series , 2020, International Ophthalmology.

[92]  K. Cai,et al.  Programmable prodrug micelle with size-shrinkage and charge-reversal for chemotherapy-improved IDO immunotherapy. , 2020, Biomaterials.

[93]  E. Stefánsson,et al.  Can postoperative dexamethasone nanoparticle eye drops replace mitomycin C in trabeculectomy? , 2020, Acta ophthalmologica.

[94]  F. Ogata,et al.  Novel Sustained-Release Drug Delivery System for Dry Eye Therapy by Rebamipide Nanoparticles , 2020, Pharmaceutics.

[95]  Qinfu Zhao,et al.  Chitosan-N-acetylcysteine modified HP-β-CD inclusion complex as a potential ocular delivery system for anti-cataract drug: Quercetin , 2020 .

[96]  S. Jacob,et al.  Emerging role of nanosuspensions in drug delivery systems , 2020, Biomaterials Research.

[97]  Jaeyun Kim,et al.  Therapeutic Contact Lens for Scavenging Excessive Reactive Oxygen Species on Ocular Surface. , 2020, ACS nano.

[98]  N. Jain,et al.  Formulation and investigation of pilocarpine hydrochloride niosomal gels for the treatment of glaucoma: intraocular pressure measurement in white albino rabbits , 2020, Drug delivery.

[99]  Q. Ping,et al.  Incorporation of ion exchange functionalized-montmorillonite into solid lipid nanoparticles with low irritation enhances drug bioavailability for glaucoma treatment , 2020, Drug delivery.

[100]  Ye Wang,et al.  Co-delivery of brinzolamide and miRNA-124 by biodegradable nanoparticles as a strategy for glaucoma therapy , 2020, Drug delivery.

[101]  Feng Cao,et al.  Functional chitosan oligosaccharide nanomicelles for topical ocular drug delivery of dexamethasone. , 2020, Carbohydrate polymers.

[102]  M. Coote,et al.  24-Month Phase I/II Clinical Trial of Bimatoprost Sustained-Release Implant (Bimatoprost SR) in Glaucoma Patients , 2019, Drugs.

[103]  M. Anwer,et al.  Preparation of levofloxacin loaded in situ gel for sustained ocular delivery: in vitro and ex vivo evaluations , 2019, Drug development and industrial pharmacy.

[104]  D. D. Nguyen,et al.  Benzoic acid derivative-modified chitosan-g-poly(N-isopropylacrylamide): Methoxylation effects and pharmacological treatments of Glaucoma-related neurodegeneration. , 2019, Journal of controlled release : official journal of the Controlled Release Society.

[105]  D. D. Nguyen,et al.  Dendritic Effects of Injectable Biodegradable Thermogels on Pharmacotherapy of Inflammatory Glaucoma‐Associated Degradation of Extracellular Matrix , 2019, Advanced healthcare materials.

[106]  Bailiang Wang,et al.  Synergistic Chemotherapy and Photodynamic Therapy of Endophthalmitis Mediated by Zeolitic Imidazolate Framework-Based Drug Delivery Systems. , 2019, Small.

[107]  P. Garg,et al.  Amphotericin B containing microneedle ocular patch for effective treatment of fungal keratitis. , 2019, International journal of pharmaceutics.

[108]  A. Ferreira,et al.  Chitosan/Hydroxyethyl cellulose inserts for sustained-release of dorzolamide for glaucoma treatment: in vitro and in vivo evaluation. , 2019, International journal of pharmaceutics.

[109]  G. Kaur,et al.  Leucaena leucocephala (Lam.) galactomannan nanoparticles: Optimization and characterization for ocular delivery in glaucoma treatment. , 2019, International journal of biological macromolecules.

[110]  Diogo B. Bitoque,et al.  Self-Assembled Multilayer Films for Time-Controlled Ocular Drug Delivery. , 2019, ACS applied bio materials.

[111]  K. Martin,et al.  Neuroprotection in Glaucoma: Towards Clinical Trials and Precision Medicine , 2019, Current eye research.

[112]  M. Yar,et al.  Medicinal prospects of antioxidants: A review. , 2019, European journal of medicinal chemistry.

[113]  S. Majumdar,et al.  Δ9-Tetrahydrocannabinol Derivative-Loaded Nanoformulation Lowers Intraocular Pressure in Normotensive Rabbits , 2019, Translational vision science & technology.

[114]  J. Sheppard,et al.  A Phase 3, Randomized, Double-Masked Study of OTX-101 Ophthalmic Solution 0.09% in the Treatment of Dry Eye Disease. , 2019, Ophthalmology.

[115]  Tianjiao Ji,et al.  Nanoscale systems for local drug delivery. , 2019, Nano today.

[116]  Xing Tang,et al.  Co-delivery of latanoprost and timolol from micelles-laden contact lenses for the treatment of glaucoma. , 2019, Journal of controlled release : official journal of the Controlled Release Society.

[117]  Bokyoung Lee,et al.  Silver nanoparticles induce reactive oxygen species-mediated cell cycle delay and synergistic cytotoxicity with 3-bromopyruvate in Candida albicans, but not in Saccharomyces cerevisiae , 2019, International journal of nanomedicine.

[118]  Yuliang Zhao,et al.  Safety Assessment of Nanomaterials to Eyes: An Important but Neglected Issue , 2019, Advanced science.

[119]  A. Quantock,et al.  Hyperlipidemia induces meibomian gland dysfunction. , 2019, The ocular surface.

[120]  Shuai Shi,et al.  Stimulus-Responsive Hydrogel for Ophthalmic Drug Delivery. , 2019, Macromolecular bioscience.

[121]  D. Zurakowski,et al.  Effect of 2 Novel Sustained-release Drug Release Systems on Bleb Fibrosis: An In Vivo Trabeculectomy Study in a Rabbit Model , 2019, Journal of glaucoma.

[122]  C. Joo,et al.  Drug-eluting contact lens containing cyclosporine-loaded cholesterol-hyaluronate micelles for dry eye syndrome , 2019, RSC advances.

[123]  Kang Zhou,et al.  Liposomes for effective drug delivery to the ocular posterior chamber , 2019, Journal of Nanobiotechnology.

[124]  I. Kaur,et al.  Bimatoprost loaded nanovesicular long-acting sub-conjunctival in-situ gelling implant: In vitro and in vivo evaluation. , 2019, Materials science & engineering. C, Materials for biological applications.

[125]  H. Salem,et al.  Development, Optimization, and In Vitro/In Vivo Characterization of Enhanced Lipid Nanoparticles for Ocular Delivery of Ofloxacin: the Influence of Pegylation and Chitosan Coating , 2019, AAPS PharmSciTech.

[126]  K. Yao,et al.  Injectable cell-encapsulating composite alginate-collagen platform with inducible termination switch for safer ocular drug delivery. , 2019, Biomaterials.

[127]  J. Németh,et al.  A Randomized, Controlled Trial of Cyclosporine A Cationic Emulsion in Pediatric Vernal Keratoconjunctivitis: The VEKTIS Study. , 2019, Ophthalmology.

[128]  T. Dada,et al.  Effect of Ultra-Small Chitosan Nanoparticles Doped with Brimonidine on the Ultra-Structure of the Trabecular Meshwork of Glaucoma Patients , 2019, Microscopy and Microanalysis.

[129]  M. Khaleel,et al.  Natamycin solid lipid nanoparticles – sustained ocular delivery system of higher corneal penetration against deep fungal keratitis: preparation and optimization , 2019, International journal of nanomedicine.

[130]  I. Bravo-Osuna,et al.  Simultaneous co‐delivery of neuroprotective drugs from multi‐loaded PLGA microspheres for the treatment of glaucoma , 2019, Journal of controlled release : official journal of the Controlled Release Society.

[131]  S. K. Yellanki,et al.  Preparation and in vivo evaluation of sodium alginate - poly (vinyl alcohol) electrospun nanofibers of forskolin for glaucoma treatment. , 2019, Pakistan journal of pharmaceutical sciences.

[132]  T. Desai,et al.  Co-Delivery of Timolol and Brimonidine with a Polymer Thin-Film Intraocular Device. , 2019, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[133]  Rania M. Hathout,et al.  Gelatinized core liposomes: A new Trojan horse for the development of a novel timolol maleate glaucoma medication. , 2019, International journal of pharmaceutics.

[134]  D. Yan,et al.  Supramolecular nanoscale drug-delivery system with ordered structure , 2019, National science review.

[135]  Y. Ko,et al.  Thermosensitive chitosan‐gelatin‐based hydrogel containing curcumin‐loaded nanoparticles and latanoprost as a dual‐drug delivery system for glaucoma treatment , 2019, Experimental eye research.

[136]  M. Coote,et al.  Intracameral Sustained-Release Bimatoprost Implant Delivers Bimatoprost to Target Tissues with Reduced Drug Exposure to Off-Target Tissues , 2019, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[137]  I. Rupenthal,et al.  Brinzolamide–loaded nanoemulsions: ex vivo transcorneal permeation, cell viability and ocular irritation tests , 2019, Pharmaceutical development and technology.

[138]  J. Lai,et al.  Amination degree of gelatin is critical for establishing structure-property-function relationships of biodegradable thermogels as intracameral drug delivery systems. , 2019, Materials science & engineering. C, Materials for biological applications.

[139]  M. Ghorab,et al.  Proniosomal gel-derived niosomes: an approach to sustain and improve the ocular delivery of brimonidine tartrate; formulation, in-vitro characterization, and in-vivo pharmacodynamic study , 2019, Drug delivery.

[140]  Yang Liu,et al.  Novel redispersible nanosuspensions stabilized by co-processed nanocrystalline cellulose–sodium carboxymethyl starch for enhancing dissolution and oral bioavailability of baicalin , 2019, International journal of nanomedicine.

[141]  D. Chattopadhyay,et al.  Utilization of Cellulose Nanocrystals (CNC) Biopolymer Nanocomposites in Ophthalmic Drug Delivery System (ODDS) , 2019, Journal of Nanotechnology Research.

[142]  C. Astete,et al.  Topical nanodelivery system of lutein for the prevention of selenite-induced cataract. , 2019, Nanomedicine : nanotechnology, biology, and medicine.

[143]  Xiangrong Song,et al.  TPGS modified nanoliposomes as an effective ocular delivery system to treat glaucoma , 2018, International journal of pharmaceutics.

[144]  Fahd M. Alsharif,et al.  Chitosan-Gelatin Hydrogel Crosslinked With Oxidized Sucrose for the Ocular Delivery of Timolol Maleate. , 2018, Journal of pharmaceutical sciences.

[145]  Xinghuai Sun,et al.  Local Delivery and Sustained‐Release of Nitric Oxide Donor Loaded in Mesoporous Silica Particles for Efficient Treatment of Primary Open‐Angle Glaucoma , 2018, Advanced healthcare materials.

[146]  Ying Huang,et al.  Thermo‐sensitive gel in glaucoma therapy for enhanced bioavailability: In vitro characterization, in vivo pharmacokinetics and pharmacodynamics study , 2018, Life sciences.

[147]  J. Tauber,et al.  A Phase II/III, randomized, double-masked, vehicle-controlled, dose-ranging study of the safety and efficacy of OTX-101 in the treatment of dry eye disease , 2018, Clinical ophthalmology.

[148]  Lei Gu,et al.  Effect of Rapamycin Microspheres in Sjögren Syndrome Dry Eye: Preparation and Outcomes , 2018, Ocular immunology and inflammation.

[149]  M. Matsusaki,et al.  Effect of deacetylation degree on controlled pilocarpine release from injectable chitosan-g-poly(N-isopropylacrylamide) carriers. , 2018, Carbohydrate polymers.

[150]  Guei-Sheung Liu,et al.  Ocular Drug Delivery: Role of Degradable Polymeric Nanocarriers for Ophthalmic Application , 2018, International journal of molecular sciences.

[151]  H. Fahmy,et al.  Treatment merits of Latanoprost/Thymoquinone – Encapsulated liposome for glaucomatus rabbits , 2018, International journal of pharmaceutics.

[152]  S. Venkatraman,et al.  Targeted therapy for the post-operative conjunctiva: SPARC silencing reduces collagen deposition , 2018, British Journal of Ophthalmology.

[153]  Juan Li,et al.  Montmorillonite/chitosan nanoparticles as a novel controlled-release topical ophthalmic delivery system for the treatment of glaucoma , 2018, International journal of nanomedicine.

[154]  Jobin Jose,et al.  Novel hydrogel-based ocular drug delivery system for the treatment of conjunctivitis , 2018, International Ophthalmology.

[155]  L. Tong,et al.  Dry eye disease and oxidative stress , 2018, Acta ophthalmologica.

[156]  D. Shah,et al.  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. , 2018, Biomaterials science.

[157]  Hu Yang,et al.  DenTimol as A Dendrimeric Timolol Analogue for Glaucoma Therapy: Synthesis and Preliminary Efficacy and Safety Assessment. , 2018, Molecular pharmaceutics.

[158]  N. Bavarsad,et al.  Dorzolamide nanoliposome as a long action ophthalmic delivery system in open angle glaucoma and ocular hypertension patients , 2018, Drug development and industrial pharmacy.

[159]  S. Nair,et al.  Sustained release timolol maleate loaded ocusert based on biopolymer composite. , 2018, International journal of biological macromolecules.

[160]  Vikramaditya G. Yadav,et al.  A stimulus-responsive, in situ-forming, nanoparticle-laden hydrogel for ocular drug delivery , 2018, Drug Delivery and Translational Research.

[161]  Rinda Devi Bachu,et al.  Ocular Drug Delivery Barriers—Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases , 2018, Pharmaceutics.

[162]  M. Shafaa,et al.  Interaction of Coenzyme Q10 with Liposomes and its Impact on Suppression of Selenite – Induced Experimental Cataract , 2018, Advanced pharmaceutical bulletin.

[163]  I. Elsayed,et al.  Enhancement of pharmacokinetic and pharmacological behavior of ocular dorzolamide after factorial optimization of self-assembled nanostructures , 2018, PloS one.

[164]  Juan Li,et al.  Controlled drug delivery for glaucoma therapy using montmorillonite/Eudragit microspheres as an ion-exchange carrier , 2018, International journal of nanomedicine.

[165]  T. Desai,et al.  Long‐term intraocular pressure reduction with intracameral polycaprolactone glaucoma devices that deliver a novel anti‐glaucoma agent , 2018, Journal of controlled release : official journal of the Controlled Release Society.

[166]  A. El-Kamel,et al.  Nanostructured lipid carriers for intraocular brimonidine localisation: development, in-vitro and in-vivo evaluation , 2018, Journal of microencapsulation.

[167]  Doaa Hegazy,et al.  Sustained ocular delivery of Dorzolamide-HCl via proniosomal gel formulation: in-vitro characterization, statistical optimization, and in-vivo pharmacodynamic evaluation in rabbits , 2018, Drug delivery.

[168]  Jingguo Li,et al.  Fabrication of a drug delivery system that enhances antifungal drug corneal penetration , 2018, Drug delivery.

[169]  Yinglan Yu,et al.  Improving the topical ocular pharmacokinetics of lyophilized cyclosporine A-loaded micelles: formulation, in vitro and in vivo studies , 2018, Drug delivery.

[170]  Xing-jie Liang,et al.  Nanomicelle‐Assisted Targeted Ocular Delivery with Enhanced Antiinflammatory Efficacy In Vivo , 2017, Advanced science.

[171]  B. Mehravi,et al.  Nanogel-based natural polymers as smart carriers for the controlled delivery of Timolol Maleate through the cornea for glaucoma. , 2017, International journal of biological macromolecules.

[172]  A. Silva,et al.  Memantine-Loaded PEGylated Biodegradable Nanoparticles for the Treatment of Glaucoma. , 2018, Small.

[173]  V. Rodilla,et al.  Ex vivo rabbit cornea diffusion studies with a soluble insert of moxifloxacin , 2018, Drug Delivery and Translational Research.

[174]  F. Chiellini,et al.  Neurotrophin-conjugated nanoparticles prevent retina damage induced by oxidative stress , 2017, Cellular and Molecular Life Sciences.

[175]  J. Brandt,et al.  Long-term Safety and Efficacy of a Sustained-Release Bimatoprost Ocular Ring. , 2017, Ophthalmology.

[176]  Xiaoting Peng,et al.  Evaluation of a photocrosslinkable hydroxyethyl chitosan hydrogel as a potential drug release system for glaucoma surgery , 2017, Journal of Materials Science: Materials in Medicine.

[177]  J. Sheu,et al.  In vitro antioxidant and anticataractogenic potential of silver nanoparticles biosynthesized using an ethanolic extract of Tabernaemontana divaricata leaves. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[178]  Hu Yang,et al.  Fast Dissolving Dendrimer Nanofiber Mats as Alternative to Eye Drops for More Efficient Antiglaucoma Drug Delivery. , 2017, ACS biomaterials science & engineering.

[179]  I. Bravo-Osuna,et al.  Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbits , 2017, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[180]  Hu Yang,et al.  Dendrimers for Ocular Drug Delivery. , 2017, Canadian journal of chemistry.

[181]  Ying Huang,et al.  Ocular Cubosome Drug Delivery System for Timolol Maleate: Preparation, Characterization, Cytotoxicity, Ex Vivo, and In Vivo Evaluation , 2017, AAPS PharmSciTech.

[182]  H. Oikawa,et al.  Creation of nano eye-drops and effective drug delivery to the interior of the eye , 2017, Scientific Reports.

[183]  M. Coote,et al.  Bimatoprost Sustained-Release Implants for Glaucoma Therapy: 6-Month Results From a Phase I/II Clinical Trial. , 2017, American journal of ophthalmology.

[184]  A. Mahmoud,et al.  PLGA Nanoparticles as Subconjunctival Injection for Management of Glaucoma , 2017, AAPS PharmSciTech.

[185]  R. Nickells,et al.  An intraocular drug delivery system using targeted nanocarriers attenuates retinal ganglion cell degeneration , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[186]  S. Chou,et al.  In vivo Pharmacological Evaluations of Pilocarpine-Loaded Antioxidant-Functionalized Biodegradable Thermogels in Glaucomatous Rabbits , 2017, Scientific Reports.

[187]  Richard T. Addo,et al.  Ocular Drug Delivery: Advances, Challenges and Applications , 2016, Springer International Publishing.

[188]  A. Mitra,et al.  Nanoparticle-based topical ophthalmic formulation for sustained release of stereoisomeric dipeptide prodrugs of ganciclovir , 2016, Drug delivery.

[189]  C. Kiparissides,et al.  Nano-carrier systems: Strategies to overcome the mucus gel barrier. , 2015, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[190]  J. Sivak,et al.  Preclinical development and ocular biodistribution of gemini-DNA nanoparticles after intravitreal and topical administration: towards non-invasive glaucoma gene therapy. , 2014, Nanomedicine : nanotechnology, biology, and medicine.

[191]  Timothy Y Chou,et al.  Ganciclovir ophthalmic gel 0.15% for the treatment of acute herpetic keratitis: background, effectiveness, tolerability, safety, and future applications , 2014, Therapeutics and clinical risk management.

[192]  Hongming Chen,et al.  Ocular Pharmacokinetics of a Novel Loteprednol Etabonate 0.4% Ophthalmic Formulation , 2014, Ophthalmology and Therapy.

[193]  J. Colin Ganciclovir ophthalmic gel, 0.15%: a valuable tool for treating ocular herpes , 2007, Clinical ophthalmology.

[194]  José Juan Escobar-Chávez,et al.  Applications of thermo-reversible pluronic F-127 gels in pharmaceutical formulations. , 2006, Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques.