Patented Formulations, Nanotherapeutics and Herbal Compound
Applications for Dry Eye : A Review

Vindhya      Pal; Sushma      Verma
doi:10.2174/1574885518666230822144922
Abstract

Background: The defining features of dry eye syndrome, a frequent tear and ocular surface multifactorial disorder, are changes in the ocular surface epithelia linked with less tear production and elevated sensitivity of the ocular surface, which trigger an inflammatory response. Aqueous deficit dry eye and evaporated dry eye are the two common types of dry eye. A few of the testing methods used to detect Dry Eye Disease are the Schirmer’s test, Tear Meniscus Volume, Tear Break-up Time, Tear Film Thickness, Meibomian Gland Infrared Meibography, Lissamine Green Staining, and Rose Bengal Staining. Hyperosmolarity and instability are the main pathogenic processes of dry eye disease. These systems are intricately linked to one another and create a "vicious circle" that never ends.
Objective: The objective of this review was to describe patented formulations, novel drug delivery systems and herbal drugs for Dry Eye Disease.
Results: Following a thorough assessment, the current study has elaborated a number of patented formulations in the form of contact lenses, biomarkers, novel approaches, and emulsions (traditional dosage forms) as well as natural medicines. In comparison to standard dosage forms, contact lenses and novel approaches have longer contact times and higher bioavailability.
Conclusion: In this paper, the diagnostic methods of dry eye disease, the outcomes of pathophysiology, herbal treatments, nanotherapeutics, and current patented medicine formulations are described.
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Graphical Abstract

[1]
Quiroz-Mercado H, Hernandez-Quintela E, Chiu KH, Henry E, Nau JA. A phase II randomized trial to evaluate the long-term (12-week) efficacy and safety of OC-01 (varenicline solution) nasal spray for dry eye disease: The MYSTIC study. Ocul Surf  2022; 24: 15-21.
 [http://dx.doi.org/10.1016/j.jtos.2021.12.007] [PMID: 34920097]

[2]
Jurišić Dukovski B, Juretić M, Bračko D, et al. Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment. Int J Pharm  2020; 576: 118979.
 [http://dx.doi.org/10.1016/j.ijpharm.2019.118979] [PMID: 31870964]

[3]
Laddha UD, Kshirsagar SJ. Formulation of nanoparticles loaded in situ gel for treatment of dry eye disease: In vitro, ex vivo and in vivo evidences. J Drug Deliv Sci Technol  2021; 61: 102112.
 [http://dx.doi.org/10.1016/j.jddst.2020.102112]

[4]
Dana R, Bradley JL, Guerin A, et al. Estimated prevalence and incidence of dry eye disease based on coding analysis of a large, all-age United States health care system. Am J Ophthalmol  2019; 202: 47-54.
 [http://dx.doi.org/10.1016/j.ajo.2019.01.026] [PMID: 30721689]

[5]
Caban M, Lewandowska U. Inhibiting effects of polyphenols on angiogenesis and epithelial-mesenchymal transition in anterior segment eye diseases. J Funct Foods  2021; 87: 104761.
 [http://dx.doi.org/10.1016/j.jff.2021.104761]

[6]
Nagai N, Otake H. Novel drug delivery systems for the management of dry eye. Adv Drug Deliv Rev  2022; 191: 114582.
 [http://dx.doi.org/10.1016/j.addr.2022.114582] [PMID: 36283491]

[7]
Mohammad Garg V, Nirmal J. , et al Topical tacrolimus Progylcosomes nano-vesicles as a potential therapy for experimental dry eye syndrome. J Pharm Sci  2022; 111(2): 479-84.
 [http://dx.doi.org/10.1016/j.xphs.2021.09.038] [PMID: 34599998]

[8]
Tong L, Beuerman R, Simonyi S, Hollander DA, Stern ME. Effects of punctal occlusion on clinical signs and symptoms and on tear cytokine levels in patients with dry eye. Ocul Surf  2016; 14(2): 233-41.
 [http://dx.doi.org/10.1016/j.jtos.2015.12.004] [PMID: 26774908]

[9]
Colligris B, Alkozi HA, Pintor J. Recent developments on dry eye disease treatment compounds. Saudi J Ophthalmol  2014; 28(1): 19-30.
 [http://dx.doi.org/10.1016/j.sjopt.2013.12.003] [PMID: 24526854]

[10]
Pflugfelder SC, de Paiva CS. The pathophysiology of dry eye disease: what we know and future directions for research. Ophthalmology  2017; 124(11): S4-S13.
 [http://dx.doi.org/10.1016/j.ophtha.2017.07.010] [PMID: 29055361]

[11]
Kattar A, Concheiro A, Alvarez-Lorenzo C. Diabetic eye: Associated diseases, drugs in clinic, and role of self-assembled carriers in topical treatment. Expert Opin Drug Deliv  2021; 18(11): 1589-607.
 [http://dx.doi.org/10.1080/17425247.2021.1953466] [PMID: 34253138]

[12]
Mohamed HB, Abd El-Hamid BN, Fathalla D, Fouad EA. Current trends in pharmaceutical treatment of dry eye disease: A review. Eur J Pharm Sci  2022; 175: 106206.
 [http://dx.doi.org/10.1016/j.ejps.2022.106206] [PMID: 35568107]

[13]
Zhang X, M VJ, Qu Y. , et al Dry eye management: Targeting the ocular surface microenvironment. Int J Mol Sci  2017; 18(7): 1398.
 [http://dx.doi.org/10.3390/ijms18071398] [PMID: 28661456]

[14]
Lemp MA. Dry eye disease: Epidemiology and pathophysiology. In: Ocular Surface Disease: Cornea, Conjunctiva and Tear Film.  Elsevier 2013; pp. 77-83.

[15]
Gunther B, Loscher F, Voss H, et al. Ophthalmic composition comprising F6H8. W.O. Patent 2019/068763, 2019.

[16]
Willcox MDP, Argüeso P, Georgiev GA, et al. TFOS DEWS II tear film report. Ocul Surf  2017; 15(3): 366-403.
 [http://dx.doi.org/10.1016/j.jtos.2017.03.006] [PMID: 28736338]

[17]
Baudouin C, Aragona P, Messmer EM, et al. Role of hyperosmolarity in the pathogenesis and management of dry eye disease: Proceedings of the OCEAN group meeting. Ocul Surf  2013; 11(4): 246-58.
 [http://dx.doi.org/10.1016/j.jtos.2013.07.003] [PMID: 24112228]

[18]
Aragona P, Giannaccare G, Mencucci R, Rubino P, Cantera E, Rolando M. Modern approach to the treatment of dry eye, a complex multifactorial disease: A P.I.C.A.S.S.O. board review. Br J Ophthalmol  2021; 105(4): 446-53.
 [http://dx.doi.org/10.1136/bjophthalmol-2019-315747] [PMID: 32703782]

[19]
Silbert JA, Bitton E, Bhagat K. Advances in diagnosis and management of dry eye disease. Adv Ophthalmol Optom  2019; 4: 13-38.
 [http://dx.doi.org/10.1016/j.yaoo.2019.04.002]

[20]
Deng Y, Wang Q, Luo Z, et al. Quantitative analysis of morphological and functional features in meibography for meibomian gland dysfunction: Diagnosis and grading. EClinicalMedicine  2021; 40: 101132.
 [http://dx.doi.org/10.1016/j.eclinm.2021.101132] [PMID: 34541482]

[21]
Lin H, Yiu SC. Dry eye disease: A review of diagnostic approaches and treatments. Saudi J Ophthalmol  2014; 28(3): 173-81.
 [http://dx.doi.org/10.1016/j.sjopt.2014.06.002] [PMID: 25278793]

[22]
Yeu E, Silverstein S, Guillon M, et al. Efficacy and safety of phospholipid nanoemulsion-based ocular lubricant for the management of various subtypes of dry eye disease: A phase IV, multicenter trial. Clin Ophthalmol  2020; 14: 2561-70.
 [http://dx.doi.org/10.2147/OPTH.S261318] [PMID: 32943837]

[23]
Leonardi A, Van Setten G, Amrane M, et al. Efficacy and safety of 0.1% cyclosporine A cationic emulsion in the treatment of severe dry eye disease: A multicenter randomized trial. Eur J Ophthalmol  2016; 26(4): 287-96.
 [http://dx.doi.org/10.5301/ejo.5000779] [PMID: 27055414]

[24]
Tauber J, Schechter BA, Bacharach J, 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. Clin Ophthalmol  2018; 12: 1921-9.
 [http://dx.doi.org/10.2147/OPTH.S175065] [PMID: 30323548]

[25]
Goldberg DF, Malhotra RP, Schechter BA, Justice A, Weiss SL, Sheppard JD. A phase 3, randomized, double-masked study of OTX-101 ophthalmic solution 0.09% in the treatment of dry eye disease. Ophthalmology  2019; 126(9): 1230-7.
 [http://dx.doi.org/10.1016/j.ophtha.2019.03.050] [PMID: 30965064]

[26]
Taylor M, Ousler G, Torkildsen G, et al. A phase 2 randomized, double-masked, placebo-controlled study of novel nonsystemic kinase inhibitor TOP1630 for the treatment of dry eye disease. Clin Ophthalmol  2019; 13: 261-75.
 [http://dx.doi.org/10.2147/OPTH.S189039] [PMID: 30858682]

[27]
Karaca EE, Özek D, Evren Kemer Ö. Comparison study of two different topical lubricants on tear meniscus and tear osmolarity in dry eye. Cont Lens Anterior Eye  2020; 43(4): 373-7.
 [http://dx.doi.org/10.1016/j.clae.2019.10.001] [PMID: 31615726]

[28]
Connor CG, Haine CL. Treatment for dry eye. U.S. Patent 2021/0008079, 2021.

[29]
Zeev MS, Miller DD, Latkany R. Diagnosis of dry eye disease and emerging technologies. Clin Ophthalmol  2014; 8: 581-90.
 [PMID: 24672224]

[30]
Palamar M, Karaca I, Onay H, Ertam I, Yagci A. Dry eye and Meibomian gland dysfunction with meibography in patients with lamellar ichthyosis. Cont Lens Anterior Eye  2018; 41(2): 154-6.
 [http://dx.doi.org/10.1016/j.clae.2017.06.001] [PMID: 28645677]

[31]
Doughty MJ. Rose bengal staining as an assessment of ocular surface damage and recovery in dry eye disease-A review. Cont Lens Anterior Eye  2013; 36(6): 272-80.
 [http://dx.doi.org/10.1016/j.clae.2013.07.008] [PMID: 23928365]

[32]
Hamrah P, Qazi Y. Meibomian gland dysfunction. U.S. Patent 9, 931, 031, 2018.

[33]
Chang JN. Cyclosporine compositions. U.S. Patent 2013/0059796, 2013.

[34]
Hou H, Wang J. Timolol maleate (TM) eye gel and preparation method thereof. C.N. Patent 102178644, 2013.

[35]
Cruzat A. Inflammatory eye disorders. W.O. Patent 2013/126602, 2013.

[36]
Beals CR, Gukasyan HJ, Ma J, Woldemussie E. Pharmaceutical compositions and procedures for treating dry eye disorders. U.S. Patent 2013/0303557, 2013.

[37]
Chang JN, Olejnik O, Firestone BA. Cyclosporine compositions. U.S. Patent 8,969,306, 2015.

[38]
Loudin JD, Franke M, Hamilton DN, Doraiswamy A, Ackermann DM. Contact lens for increasing tear production. C.A. Patent 2,965,514, 2016.

[39]
Graham RS, Tien WL, Attar M, Schiffman R, Morgan A. Cyclosporine compositions. U.S. Patent 9,561,178, 2017.

[40]
Badawi P. Dry eye treatment apparatus and methods. U.S. Patent 9, 724, 230, 2017.

[41]
Hellstrom HR, Agris CH. Treatment of dry eye disease with parasympathetic and anti-sympathetic agents. W.O. Patent 2017/210158, 2017.

[42]
Gunther B, Scherer D, Xu H. Compositions comprising Tacrolimus for the treatment of intraocular inflammatory eye diseases. W.O. Patent 2018/114557, 2018.

[43]
Horn G. Artificial tears, contact lens and drug vehicle compositions and methods of use thereof. U.S. Patent 2018/0098937, 2018.

[44]
Kim MJ. Pharmaceutical composition for preventing and treating dry eye diseases, containing Imatinib as active ingredient. U.S. Patent 10,231,971, 2019.

[45]
Sharma MK, Raghuveera HG, Upadhyay SC, Narayan NC, Narshimham PVS, Kumar A. Pharmaceutical composition of Lifitegrast. W.O. Patent 2019/171260, 2019.

[46]
Likitlersuang S, Parashar A, Pujara CP, Kelly WF. Preservative free brimonidine and timolol solutions. U.S. Patent 10,792,288, 2020.

[47]
Clark D, Brady T, Macdonald S, Machatha SG. Formulations for treatment of dry eye disease. U.S. Patent 2020/0121591, 2020.

[48]
Clark D, Macdonald S, Machatha SG, Kjems LL. Ophthalmic formulations and uses thereof. WO Patent 2020/198064, 2020.

[49]
Liang B, Peng H, Zhu J, Yuan X. In-situ gel containing cyclosporin micelles as sustained ophthalmic drug delivery system. W.O. Patent 2021/032073, 2021.

[50]
Brady T, Machatha SG, Brockman A. Dry eye disease biomarkers and their use for treatment. W.O. Patent 2021/248031, 2021.

[51]
Ackermann DM, Loudin JD. Nasal stimulation devices and methods for treating dry eye. U.S. Patent 2021/0236809, 2021.

[52]
Leo CS, Krösser S, Schlüter T, Meides A. Ophthalmic composition for treatment of dry eye disease. U.S. Patent 11,413,323, 2022.

[53]
Takruri H. Aqueous suspensions of cyclosporin. U.S. Patent 11,324,800, 2022.

[54]
Gunther B, Scherer D, Xu H. Compositions comprising Tacrolimus for the treatment of intraocular inflammatory eye diseases. U.S. Patent 2022/0079925, 2022.

[55]
Yücel OE, Ulus ND. Efficacy and safety of topical cyclosporine A 0.05% in vernal keratoconjunctivitis. Singapore Med J  2016; 57(9): 507-10.
 [http://dx.doi.org/10.11622/smedj.2015161] [PMID: 26768065]

[56]
Baudouin C, de la Maza MS, Amrane M, et al. One-year efficacy and safety of 0.1% cyclosporine A cationic emulsion in the treatment of severe dry eye disease. Eur J Ophthalmol  2017; 27(6): 678-85.
 [http://dx.doi.org/10.5301/ejo.5001002] [PMID: 28708219]

[57]
Sheppard J, Bergmann M, Schechter BA, Luchs J, Ogundele A, Karpecki P. Phase 3 efficacy (worse-eye analysis) and long-term safety evaluation of OTX-101 in patients with keratoconjunctivitis sicca. Clin Ophthalmol  2021; 15: 129-40.
 [http://dx.doi.org/10.2147/OPTH.S279364] [PMID: 33469259]

[58]
Tauber J, Karpecki P, Latkany R, et al. OPUS-2 Investigators. Lifitegrast ophthalmic solution 5.0% versus placebo for treatment of dry eye disease: Results of the randomized phase III OPUS-2 study. Ophthalmology  2015; 122(12): 2423-31.
 [http://dx.doi.org/10.1016/j.ophtha.2015.08.001] [PMID: 26365210]

[59]
Srinivasan S, Manoj V. A decade of effective dry eye disease management with Systane Ultra (polyethylene glycol/propylene glycol with hydroxypropyl guar) lubricant eye drops. Clin Ophthalmol  2021; 15: 2421-35.
 [http://dx.doi.org/10.2147/OPTH.S294427] [PMID: 34135570]

[60]
Ohashi Y, Ebihara N, Fujishima H, et al. A randomized, placebo-controlled clinical trial of tacrolimus ophthalmic suspension 0.1% in severe allergic conjunctivitis. J Ocul Pharmacol Ther  2010; 26(2): 165-74.
 [http://dx.doi.org/10.1089/jop.2009.0087] [PMID: 20307214]

[61]
Gupta PK, Asbell P, Sheppard J. Current and future pharmacological therapies for the management of dry eye. Eye Contact Lens  2020; 46(2): S64-9.
 [http://dx.doi.org/10.1097/ICL.0000000000000666] [PMID: 31625981]

[62]
Yang C-C, Su S-H, Ho T-J. Retrospective evaluation of the curative effect of traditional Chinese medicine on dry eye disease. Tzu-Chi Med J  2021; 33(4): 365-9.
 [http://dx.doi.org/10.4103/tcmj.tcmj_281_20] [PMID: 34760632]

[63]
Huang JY, Yeh PT, Hou YC. A randomized, double-blind, placebo-controlled study of oral antioxidant supplement therapy in patients with dry eye syndrome. Clin Ophthalmol  2016; 10: 813-20.
 [PMID: 27274185]

[64]
Gao K, Liu M, Cao J, et al. Protective effects of Lycium barbarum polysaccharide on 6-OHDA-induced apoptosis in PC12 cells through the ROS-NO pathway. Molecules  2014; 20(1): 293-308.
 [http://dx.doi.org/10.3390/molecules20010293] [PMID: 25547727]

[65]
Yang J, Wei Y, Ding J, Li Y, Ma J, Liu J. Research and application of lycii fructus in medicinal field. Chin Herb Med  2018; 10(4): 339-52.
 [http://dx.doi.org/10.1016/j.chmed.2018.08.006]

[66]
Manthey AL, Chiu K, So KF. Effects of Lycium barbarum on the Visual System. Int Rev Neurobiol  2017; 135: 1-27.
 [http://dx.doi.org/10.1016/bs.irn.2017.02.002] [PMID: 28807155]

[67]
Adel IM, ElMeligy MF, Abdelkhalek AA, Elkasabgy NA. Design and characterization of highly porous curcumin loaded freeze-dried wafers for wound healing. Eur J Pharm Sci  2021; 164: 105888.
 [http://dx.doi.org/10.1016/j.ejps.2021.105888] [PMID: 34044118]

[68]
Fernández-Moriano C, González-Burgos E, Gómez-Serranillos MP. Curcumin: Current evidence of its therapeutic potential as a lead candidate for anti-inflammatory drugs-An overview. In: Discovery and Development of Anti-Inflammatory Agents from Natural Products.  Elsevier 2019; pp. 7-59.

[69]
Liu XF, Hao JL, Xie T, et al. Curcumin, a potential therapeutic candidate for anterior segment eye diseases: A review. Front Pharmacol  2017; 8: 66.
 [http://dx.doi.org/10.3389/fphar.2017.00066] [PMID: 28261099]

[70]
Mirzaei H, Shakeri A, Rashidi B, Jalili A, Banikazemi Z, Sahebkar A. Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies. Biomed Pharmacother  2017; 85: 102-12.
 [http://dx.doi.org/10.1016/j.biopha.2016.11.098] [PMID: 27930973]

[71]
Duan Y, Cai X, Du H, Zhai G. Novel in situ gel systems based on P123/TPGS mixed micelles and gellan gum for ophthalmic delivery of curcumin. Colloids Surf B Biointerfaces  2015; 128: 322-30.
 [http://dx.doi.org/10.1016/j.colsurfb.2015.02.007] [PMID: 25707750]

[72]
Liu CH, Lee GW, Wu WC, Wang CC. Encapsulating curcumin in ethylene diamine-β-cyclodextrin nanoparticle improves topical cornea delivery. Colloids Surf B Biointerfaces  2020; 186: 110726.
 [http://dx.doi.org/10.1016/j.colsurfb.2019.110726] [PMID: 31862560]

[73]
Lakhani P, Patil A, Taskar P, Ashour E, Majumdar S. Curcumin-loaded Nanostructured Lipid Carriers for ocular drug delivery: Design optimization and characterization. J Drug Deliv Sci Technol  2018; 47: 159-66.
 [http://dx.doi.org/10.1016/j.jddst.2018.07.010] [PMID: 32601526]

[74]
Lee TG, Hyun SW, Jo K, et al. Achyranthis radix extract improves urban particulate matter-induced dry eye disease. Int J Environ Res Public Health  2019; 16(18): 3229.
 [http://dx.doi.org/10.3390/ijerph16183229] [PMID: 31487776]

[75]
Jiang D, Liu X, Hu J. Topical administration of Esculetin as a potential therapy for experimental dry eye syndrome. Eye  2017; 31(12): 1724-32.
 [http://dx.doi.org/10.1038/eye.2017.117] [PMID: 28643798]

[76]
Chen HC, Chen ZY, Wang TJ, et al. Herbal supplement in a buffer for dry eye syndrome treatment. Int J Mol Sci  2017; 18(8): 1697.
 [http://dx.doi.org/10.3390/ijms18081697] [PMID: 28771187]

[77]
Rajendran P, Rengarajan T, Nandakumar N, Palaniswami R, Nishigaki Y, Nishigaki I. Kaempferol, a potential cytostatic and cure for inflammatory disorders. Eur J Med Chem  2014; 86: 103-12.
 [http://dx.doi.org/10.1016/j.ejmech.2014.08.011] [PMID: 25147152]

[78]
Xie G, Xu Q, Li R, et al. Chemical profiles and quality evaluation of Buddleja officinalis flowers by HPLC-DAD and HPLC-Q-TOF-MS/MS. J Pharm Biomed Anal  2019; 164: 283-95.
 [http://dx.doi.org/10.1016/j.jpba.2018.10.030] [PMID: 30412801]

[79]
Wang F, Peng QH, Yao XL, Wu QL, Li D. Effect of Buddleia flavonoids drug-containing plasma on the expression of STAT1 phosphoprotein in lacrimal gland epithelial cells in vitro. Int J Ophthalmol  2010; 3(1): 32-5.
 [PMID: 22553513]

[80]
Peng QH, Yao XL, Wu QL, Tan HY, Zhang JR. Effects of extract of Buddleja officinalis eye drops on androgen receptors of lacrimal gland cells of castrated rats with dry eye. Int J Ophthalmol  2010; 3(1): 43-8.
 [PMID: 22553515]

[81]
Yao XL, Peng QH, Peng J, et al. Effects of extract of Buddleja officinalis on partial inflammation of lacrimal gland in castrated rabbits with dry eye. Int J Ophthalmol  2010; 3(2): 114-9.
 [PMID: 22553532]

[82]
Aggarwal S, Peck T, Olsakovsky L. Dry eye syndrome in menopause and perimenopausal age group. J Midlife Health  2017; 8(2): 51-4.
 [http://dx.doi.org/10.4103/jmh.JMH_41_17] [PMID: 28706404]

[83]
Zhang C, Li K, Yang Z, Wang Y, Si H. The effect of the aqueous extract of Bidens pilosa L. on androgen deficiency dry eye in rats. Cell Physiol Biochem  2016; 39(1): 266-77.
 [http://dx.doi.org/10.1159/000445622] [PMID: 27337217]

[84]
Singh S, Moksha L, Sharma N, Titiyal JS, Biswas NR, Velpandian T. Development and evaluation of animal models for sex steroid deficient dry eye. J Pharmacol Toxicol Methods  2014; 70(1): 29-34.
 [http://dx.doi.org/10.1016/j.vascn.2014.03.004] [PMID: 24632522]

[85]
Wu H, Lin L, Du X, et al. Study on the potential effective ingredients of Xiaosheng prescription for dry eye disease. Biomed Pharmacother  2020; 127: 110051.
 [http://dx.doi.org/10.1016/j.biopha.2020.110051] [PMID: 32428832]

[86]
Song SJ, Hyun SW, Lee TG, et al. Topical application of Liriope platyphylla extract attenuates dry eye syndrome induced by particulate matter. J Ophthalmol  2019; 2019: 1-7.
 [http://dx.doi.org/10.1155/2019/1429548] [PMID: 31915539]

[87]
Parrasia S, Galletta E, La Spina M, et al. Long-term pterostilbene supplementation of a high-fat diet increases adiponectin expression in the subcutaneous white adipose tissue. Nutraceuticals  2022; 2(2): 102-15.
 [http://dx.doi.org/10.3390/nutraceuticals2020008]

[88]
Li J, Ruzhi Deng, Hua X, et al. Blueberry component pterostilbene protects corneal epithelial cells from inflammation via anti-oxidative pathway. Sci Rep  2016; 6(1): 19408.
 [http://dx.doi.org/10.1038/srep19408] [PMID: 26762881]

[89]
Hu L, Hu Z, Yu Y, et al. Preparation and characterization of a pterostilbene-peptide prodrug nanomedicine for the management of dry eye. Int J Pharm  2020; 588: 119683.
 [http://dx.doi.org/10.1016/j.ijpharm.2020.119683] [PMID: 32712251]

[90]
Chien KJ, Horng CT, Huang YS, et al. Effects of Lycium barbarum (goji berry) on dry eye disease in rats. Mol Med Rep  2018; 17(1): 809-18.
 [PMID: 29115477]

[91]
Allegri P, Mastromarino A, Neri P. Management of chronic anterior uveitis relapses: Efficacy of oral phospholipidic curcumin treatment. Long-term follow-up. Clin Ophthalmol  2010; 4: 1201-6.
 [PMID: 21060672]

[92]
Xu J, Chen S, Hao X, et al. Traditional chinese medicine xiaosheng Powder for dry eye disease. Medicine  2020; 99(35): e22019.
 [http://dx.doi.org/10.1097/MD.0000000000022019] [PMID: 32871956]

[93]
Campos PM, Petrilli R, Lopez RFV. The prominence of the dosage form design to treat ocular diseases. Int J Pharm  2020; 586: 119577.
 [http://dx.doi.org/10.1016/j.ijpharm.2020.119577] [PMID: 32622806]

[94]
Prata AI, Coimbra P, Pina ME. Preparation of dexamethasone ophthalmic implants: A comparative study of in vitro release profiles. Pharm Dev Technol  2018; 23(3): 218-24.
 [http://dx.doi.org/10.1080/10837450.2017.1306560] [PMID: 28300463]

[95]
Akhter S, Anwar M, Siddiqui MA, et al. Improving the topical ocular pharmacokinetics of an immunosuppressant agent with mucoadhesive nanoemulsions: Formulation development, in-vitro and in-vivo studies. Colloids Surf B Biointerfaces  2016; 148: 19-29.
 [http://dx.doi.org/10.1016/j.colsurfb.2016.08.048] [PMID: 27591567]

[96]
Madni A, Rahem MA, Tahir N, et al. Non-invasive strategies for targeting the posterior segment of eye. Int J Pharm  2017; 530(1-2): 326-45.
 [http://dx.doi.org/10.1016/j.ijpharm.2017.07.065] [PMID: 28755994]

[97]
Maulvi FA, Desai AR, Choksi HH, et al. Effect of surfactant chain length on drug release kinetics from microemulsion-laden contact lenses. Int J Pharm  2017; 524(1-2): 193-204.
 [http://dx.doi.org/10.1016/j.ijpharm.2017.03.083] [PMID: 28366804]

[98]
Holland EJ, Darvish M, Nichols KK, Jones L, Karpecki PM. Efficacy of topical ophthalmic drugs in the treatment of dry eye disease: A systematic literature review. Ocul Surf  2019; 17(3): 412-23.
 [http://dx.doi.org/10.1016/j.jtos.2019.02.012] [PMID: 30844466]

[99]
Onugwu AL, Nwagwu CS, Onugwu OS, et al. Nanotechnology based drug delivery systems for the treatment of anterior segment eye diseases. J Control Release  2023; 354: 465-88.
 [http://dx.doi.org/10.1016/j.jconrel.2023.01.018] [PMID: 36642250]

[100]
Morsi N, Ghorab D, Refai H, Teba H. Ketoroloac tromethamine loaded nanodispersion incorporated into thermosensitive in situ gel for prolonged ocular delivery. Int J Pharm  2016; 506(1-2): 57-67.
 [http://dx.doi.org/10.1016/j.ijpharm.2016.04.021] [PMID: 27091293]

[101]
Wang TZ, Liu XX, Wang SY, et al. Engineering advanced drug delivery systems for dry eye: A review. Bioengineering  2022; 10(1): 53.
 [http://dx.doi.org/10.3390/bioengineering10010053] [PMID: 36671625]

[102]
Narayana S, Ahmed MG, Gowda BHJ, et al. Recent advances in ocular drug delivery systems and targeting VEGF receptors for management of ocular angiogenesis: A comprehensive review. Future J Pharm Sci  2021; 7(1): 186.
 [http://dx.doi.org/10.1186/s43094-021-00331-2]

[103]
Gote V, Sikder S, Sicotte J, Pal D. Ocular drug delivery: Present innovations and future challenges. J Pharmacol Exp Ther  2019; 370(3): 602-24.
 [http://dx.doi.org/10.1124/jpet.119.256933] [PMID: 31072813]

[104]
Cholkar K, Gilger BC, Mitra AK. Topical, aqueous, clear cyclosporine formulation design for anterior and posterior ocular delivery. Transl Vis Sci Technol  2015; 4(3): 1.
 [http://dx.doi.org/10.1167/tvst.4.3.1] [PMID: 25964868]

[105]
Shen Lee B, Toyos M, Karpecki P, Schiffbauer J, Sheppard J. Selective pharmacologic therapies for dry eye disease treatment: Efficacy, tolerability, and safety data review from preclinical studies and pivotal trials. Ophthalmol Ther  2022; 11(4): 1333-69.
 [http://dx.doi.org/10.1007/s40123-022-00516-9] [PMID: 35608780]

[106]
Torres-Luna C, Fan X, Domszy R, Hu N, Wang NS, Yang A. Hydrogel-based ocular drug delivery systems for hydrophobic drugs. Eur J Pharm Sci  2020; 154: 105503.
 [http://dx.doi.org/10.1016/j.ejps.2020.105503] [PMID: 32745587]

[107]
Wróblewska KB, Jadach B, Muszalska-Kolos I. Progress in drug formulation design and delivery of medicinal substances used in ophthalmology. Int J Pharm  2021; 607: 121012.
 [http://dx.doi.org/10.1016/j.ijpharm.2021.121012] [PMID: 34400274]

[108]
Yu S, Wang QM, Wang X, et al. Liposome incorporated ion sensitive in situ gels for opthalmic delivery of timolol maleate. Int J Pharm  2015; 480(1-2): 128-36.
 [http://dx.doi.org/10.1016/j.ijpharm.2015.01.032] [PMID: 25615987]

[109]
Karn PR, Cho W, Park HJ, Park JS, Hwang SJ. Characterization and stability studies of a novel liposomal cyclosporin A prepared using the supercritical fluid method: Comparison with the modified conventional Bangham method. Int J Nanomedicine  2013; 8: 365-77.
 [PMID: 23378759]

[110]
Karn PR, Kim HD, Kang H, Sun BK, Jin SE, Hwang SJ. 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  2014; 9: 3791-800.
 [PMID: 25143728]

[111]
Varela-Fernández R, García-Otero X, Díaz-Tomé V, et al. Lactoferrin-loaded nanostructured lipid carriers (NLCs) as a new formulation for optimized ocular drug delivery. Eur J Pharm Biopharm  2022; 172: 144-56.
 [http://dx.doi.org/10.1016/j.ejpb.2022.02.010] [PMID: 35183717]

[112]
Yu A, Shi H, Liu H, et al. Mucoadhesive dexamethasone-glycol chitosan nanoparticles for ophthalmic drug delivery. Int J Pharm  2020; 575: 118943.
 [http://dx.doi.org/10.1016/j.ijpharm.2019.118943] [PMID: 31830575]

[113]
Kovačević AB, Müller RH, Keck CM. Formulation development of lipid nanoparticles: Improved lipid screening and development of tacrolimus loaded nanostructured lipid carriers (NLC). Int J Pharm  2020; 576: 118918.
 [http://dx.doi.org/10.1016/j.ijpharm.2019.118918] [PMID: 31870954]

[114]
Ban J, Zhang Y, Huang X, et al. Corneal permeation properties of a charged lipid nanoparticle carrier containing dexamethasone. Int J Nanomedicine  2017; 12: 1329-39.
 [http://dx.doi.org/10.2147/IJN.S126199] [PMID: 28243093]

[115]
Åhlén M, Tummala GK, Mihranyan A. Nanoparticle-loaded hydrogels as a pathway for enzyme-triggered drug release in ophthalmic applications. Int J Pharm  2018; 536(1): 73-81.
 [http://dx.doi.org/10.1016/j.ijpharm.2017.11.053] [PMID: 29180255]

[116]
Nagai N, Ishii M, Seiriki R, et al. Novel sustained-release drug delivery system for dry eye therapy by rebamipide nanoparticles. Pharmaceutics  2020; 12(2): 155.
 [http://dx.doi.org/10.3390/pharmaceutics12020155] [PMID: 32075200]

[117]
Gugleva V, Titeva S, Ermenlieva N, et al. Development and evaluation of doxycycline niosomal thermoresponsive in situ gel for ophthalmic delivery. Int J Pharm  2020; 591: 120010.
 [http://dx.doi.org/10.1016/j.ijpharm.2020.120010] [PMID: 33132152]

[118]
Gugleva V, Titeva S, Rangelov S, Momekova D. Design and in vitro evaluation of doxycycline hyclate niosomes as a potential ocular delivery system. Int J Pharm  2019; 567: 118431.
 [http://dx.doi.org/10.1016/j.ijpharm.2019.06.022] [PMID: 31207279]
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DOI https://dx.doi.org/10.2174/1574885518666230822144922	Print ISSN 1574-8855
Publisher Name Bentham Science Publisher	Online ISSN 2212-3903
Current Drug Therapy

Patented Formulations, Nanotherapeutics and Herbal Compound Applications for Dry Eye : A Review

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