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First published online May 25, 2023

Polysaccharides polymers for glaucoma treatment-a review


One of the major challenges in preventing glaucoma progression is patient compliance with medication regimens. Since conventional ophthalmic dosage forms have numerous limitations, researchers have been intensively working on developing polymers-based delivery systems for glaucoma drugs. Specifically, research and development efforts have increased using polysaccharide polymers such as sodium alginate, cellulose, β-cyclodextrin, hyaluronic acid, chitosan, pectin, gellan gum, galactomannans for sustained release to the eye to overcome treatment challenges, showing promise in improving drug release and delivery, patient experience, and treatment compliance. In the recent past, multiple research groups have successfully designed sustained drug delivery systems, promoting the efficacy as well as the feasibility of glaucoma drugs with single/combinations of polysaccharides to eliminate the drawbacks associated with the glaucoma treatment. Naturally available polysaccharides, when used as drug vehicles can increase the retention time of eye drops on the ocular surface, leading to improved drug absorption and bioavailability. Additionally, some polysaccharides can form gels or matrices that can release drugs slowly over time, providing sustained drug delivery and reducing the need for frequent dosing. Thus, this review aims to provide an overview of the pre-clinical and clinical studies of polysaccharide polymers applied for glaucoma treatment along with their therapeutic outcomes.

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1. Patel KD, Silva LB, Park Y, et al. Recent advances in drug delivery systems for glaucoma treatment. Mater Today Nano 2022; 18: 100178.
2. Wu Y, Szymanska M, Hu Y, et al. Measures of disease activity in glaucoma. Biosens Bioelectron 2022; 196: 113700.
3. W. H. Organization, others. World report on vision. Geneva: World Health Organization; 2019, (2020).
4. Muramatsu C, Hayashi Y, Sawada A, et al. Detection of retinal nerve fiber layer defects on retinal fundus images for early diagnosis of glaucoma. J Biomed Opt 2010; 15: 16021.
5. Chandramohan H, Wan Abdul Halim WH, Azizi HA, et al. Quality of Life and Severity of Glaucoma: A Study Using Glaucol-36 Questionnaire at Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Int Med J 2017; 24: 61–64.
6. Lazcano-Gomez G, delos Angeles Ramos-Cadena M, Torres-Tamayo M, et al. J.Jimenez-Román, Cost of glaucoma treatment in a developing country over a 5-year period. Medicine (Baltimore) 2016; 95: 1–5.
7. Varma R, Lee PP, Goldberg I,. et al. An assessment of the health and economic burdens of glaucoma. Am J Ophthalmol 2011; 152: 515–522.
8. Al-Shohani ADH. Hydrogel Formulations for Ophthalmic Delivery, UCL. London: University College, 2017.
9. Urtti A. Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv Drug Deliv Rev 2006; 58: 1131–1135.
10. Sponsel WE, Paris G, Trigo Y,. et al. Comparative effects of latanoprost (Xalatan) and unoprostone (rescula) in patients with open-angle glaucoma and suspected glaucoma. Am J Ophthalmol 2002; 134: 552–559.
11. Priluck AZ, Dietze J. Ophthalmologist and optometrist glaucoma prescribing patterns based on 2015 medicare part D data. Ophthalmol Glaucoma 2019; 2: 63–66.
12. Ziadi A, Ozmaie S, Asghari A,. et al. Effect of topically applied 0.5\% apraclonidine versus 0.5\% timolol maleate on intraocular pressure of healthy horses. J Equine Vet Sci 2022; 111: 103886.
13. Okumura N, Okazaki Y, Inoue R, et al. Rho-associated kinase inhibitor eye drop (Ripasudil) transiently alters the morphology of corneal endothelial cells. Investig Ophthalmol Vis Sci 2015; 56: 7560–7567.
14. Han SB, Liu Y-C, Mohamed-Noriega K,. et al. Application of novel drugs for corneal cell regeneration. J Ophthalmol 2018; 2018: 1–9.
15. Noecker R. Effects of common ophthalmic preservatives on ocular health. Adv Ther 2001; 18: 205–215.
16. Wise JB. Ten year results of laser trabeculoplasty: does the laser avoid glaucoma surgery or merely defer it? Eye 1987; 1: 45–50.
17. Ayyala RS, Michelini-Norris B, Flores A, et al. Comparison of different biomaterials for glaucoma drainage devices: part 2. Arch Ophthalmol 2000; 118: 1081–1084.
18. Skuta GL, Parrish II RK. Wound healing in glaucoma filtering surgery. Surv Ophthalmol 1987; 32: 149–170.
19. Zhao X, Si J, Huang D, et al. Application of star poly (ethylene glycol) derivatives in drug delivery and controlled release. J Control Release 2020; 323: 565–577.
20. Ni Z, Yu H, Wang L, et al. Recent research progress on polyphosphazene-based drug delivery systems. J Mater Chem B 2020; 8: 1555–1575.
21. Besford QA, Cavalieri F, Caruso F. Glycogen as a building block for advanced biological materials. Adv Mater 2020; 32: 1904625.
22. Allyn MM, Luo RH, Hellwarth EB,. et al. Considerations for polymers used in ocular drug delivery. Front Med ; n.d; 8: 2963.
23. ElHoffy NM, Azim EAA, Hathout RM, et al. Glaucoma: management and future perspectives for nanotechnology-based treatment modalities. Eur J Pharm Sci 2021; 158: 105648.
24. Rabea EI, Badawy ME-T, VStevens C, et al. Chitosan as antimicrobial agent: applications and mode of action. Biomacromolecules 2003; 4: 1457–1465.
25. Liu J, Zhan X, Wan J, et al. Review for carrageenan-based pharmaceutical biomaterials: favourable physical features versus adverse biological effects. Carbohydr Polym 2015; 121: 27–36.
26. Zia KM, Tabasum S, Khan MF, et al. Recent trends on gellan gum blends with natural and synthetic polymers: a review. Int J Biol Macromol 2018; 109: 1068–1087.
27. Freitas CMP, Coimbra JSR, Souza VGL,. et al. Structure and applications of pectin in food, biomedical, and pharmaceutical industry: a review. Coatings 2021; 11: 922.
28. Zarrintaj P, Manouchehri S, Ahmadi Z, et al. Agarose-based biomaterials for tissue engineering. Carbohydr Polym 2018; 187: 66–84.
29. Lee KY, Mooney DJ. Alginate: properties and biomedical applications. Prog Polym Sci 2012; 37: 106–126.
30. Sun B, Zhang M, Shen J, et al. Applications of cellulose-based materials in sustained drug delivery systems. Curr Med Chem 2019; 26: 2485–2501.
31. Jiang T, Duan Q, Zhu J, et al. Starch-based biodegradable materials: challenges and opportunities. Adv Ind Eng Polym Res 2020; 3: 8–18.
32. Kianersi S, Solouk A, Saber-Samandari S, et al. Alginate nanoparticles as ocular drug delivery carriers. J Drug Deliv Sci Technol 2021; 66: 102889.
33. Gupta H, Aqil M, Khar RK, et al. An alternative in situ gel-formulation of levofloxacin eye drops for prolong ocular retention. J Pharm & Bioallied Sci 2015; 7: 9.
34. Nunes C, Silva L, Fernandes AP, et al. Occurrence of cellobiose residues directly linked to galacturonic acid in pectic polysaccharides. Carbohydr Polym 2012; 87: 620–626.
35. Lara-Espinoza C, Carvajal-Millán E, Balandrán-Quintana R, et al. Pectin and pectin-based composite materials: beyond food texture. Molecules 2018; 23: 942.
36. Yapar EA, Durgun ME, Esentürk I, et al. Herbal bioactives for ocular drug delivery systems, in: Herb. Bioact. Drug Deliv. Syst., Elsevier, 2022: pp. 25–61.
37. Grassiri B, Zambito Y, Bernkop-Schnürch A. Strategies to prolong the residence time of drug delivery systems on ocular surface. Adv Colloid Interface Sci 2021; 288: 102342.
38. Cheng K-J, Hsieh C-M, Nepali K,. et al. Ocular disease therapeutics: design and delivery of drugs for diseases of the eye. J Med Chem 2020; 63: 10533–10593.
39. Kumara BN, Shambhu R, Prasad KS. Why chitosan could be apt candidate for glaucoma drug delivery-an overview. Int J Biol Macromol 2021; 176: 47–65.
40. Hon DN-S. Cellulose and its derivatives: structures, reactions, and medical uses, in: Polysaccharides Med. Appl., Routledge, 2017: pp. 87–105.
41. Gupta B, Mishra V, Gharat S, et al. Cellulosic polymers for enhancing drug bioavailability in ocular drug delivery systems. Pharmaceuticals 2021; 14: 1201.
42. Vendrusculo CT, Pereira JL, Scamparini ARP. Gellan gum: production and properties. In: Nishinari K, Doi E (eds) Food hydrocoll. Struct. Prop. Funct. Boston, MA: Springer US, 1993, pp.91–95.
43. Bacelar AH, Silva-Correia J, Oliveira JM,. et al. Recent progress in gellan gum hydrogels provided by functionalization strategies. J Mater Chem B 2016; 4: 6164–6174.
44. Milivojevic M, Pajic-Lijakovic I, Bugarski B, et al. Gellan gum in drug delivery applications. Nat Polysaccharides Drug Deliv Biomed Appl 2019; 5: 145–186.
45. Prajapati VD, Maheriya PM, Roy SD. Locust bean gum-derived hydrogels, in: Plant Algal Hydrogels Drug Deliv. Regen. Med., Elsevier, 2021: pp. 217–260.
46. Yadav H, Maiti S. Research progress in galactomannan-based nanomaterials: synthesis and application. Int J Biol Macromol 2020; 163: 2113–2126.
47. Matencio A, Caldera F, Cecone C, et al. Cyclic oligosaccharides as active drugs, an updated review. Pharmaceuticals 2020; 13: 281.
48. Sandilya AA, Natarajan U, Priya MH. Molecular view into the cyclodextrin cavity: structure and hydration. ACS Omega 2020; 5: 25655–25667.
49. Asim MH, Ijaz M, Mahmood A, et al. Thiolated cyclodextrins: mucoadhesive and permeation enhancing excipients for ocular drug delivery. Int J Pharm 2021; 599: 120451.
50. Russo E, Selmin F, Baldassari S, et al. A focus on mucoadhesive polymers and their application in buccal dosage forms. J Drug Deliv Sci Technol 2016; 32: 113–125.
51. Jawadi Z, Yang C, Haidar ZS, et al. Bio-Inspired Muco-adhesive polymers for drug delivery applications. Polymers (Basel) 2022; 14: 5459.
52. Zhang X, Wei D, Xu Y,. et al. Hyaluronic acid in ocular drug delivery. Carbohydr Polym 2021; 264: 118006.
53. Chawananorasest K, Saengtongdee P, Kaemchantuek P. Extraction and characterization of tamarind (Tamarind indica L.) seed polysaccharides (TSP) from three difference sources. Molecules 2016; 21: 775.
54. deCastro MA, Prata WM, Cunha AS. Tamarind seed polysaccharide (TSP) uses in ophthalmic drug delivery. Rev Ciências Farm Básica e Apl 2022; 43: 1–10.
55. Jonas JB. Role of cerebrospinal fluid pressure in the pathogenesis of glaucoma. Acta Ophthalmol 2011; 89: 505–514.
56. Rocha-Sousa A, Rodrigues-Araújo J, Gouveia P, et al. New therapeutic targets for intraocular pressure lowering. Int Sch Res Not 2013; 2013: 1–4.
57. Tse AP, Shah M, Jamal N,. et al. Glaucoma treatment adherence at a United Kingdom general practice. Eye 2016; 30: 1118–1122.
58. Hirani A, Grover A, Lee YW, et al. Polymer-based therapies for posterior segment ocular disease. J Biomol Res Ther 2013; 3: e122.
59. Mittal N, Kaur G. Leucaena leucocephala (Lam.) galactomannan nanoparticles: optimization and characterization for ocular delivery in glaucoma treatment. Int J Biol Macromol 2019; 139: 1252–1262.
60. Jain N, Verma A, Jain N. Formulation and investigation of pilocarpine hydrochloride niosomal gels for the treatment of glaucoma: intraocular pressure measurement in white albino rabbits. Drug Deliv 2020; 27: 888–899.
61. Durak S, Esmaeili Rad M, Alp Yetisgin A, et al. Niosomal drug delivery systems for ocular disease—recent advances and future prospects. Nanomaterials 2020; 10: 1191.
62. Mujoriya RZ, Dhamandeb K, Bodla RB. Niosomal drug delivery system—a review. Int j Appl Pharm 2011; 3: 7–10.
63. Allam A, Elsabahy M, ElBadry M,. et al. Betaxolol-loaded niosomes integrated within pH-sensitive in situ forming gel for management of glaucoma. Int J Pharm 2021; 598: 120380.
64. Ramadan AA, Eladawy SA, El-Enin ASMA,. et al. Development and investigation of timolol maleate niosomal formulations for the treatment of glaucoma. J Pharm Investig 2020; 50: 59–70.
65. Maulvi FA, Soni TG, Shah DO. Extended release of timolol from ethyl cellulose microparticles laden hydrogel contact lenses. Open Pharm Sci J 2015; 2: 1–12.
66. Desai AR, Maulvi FA, Pandya MM, 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. Biomater Sci 2018; 6: 1580–1591.
67. El-Feky YA, Fares AR, Zayed G, et al. Repurposing of nifedipine loaded in situ ophthalmic gel as a novel approach for glaucoma treatment. Biomed & Pharmacother 2021; 142: 112008.
68. Russo G, Grumetto L, Baert M,. et al. Comprehensive two-dimensional liquid chromatography as a biomimetic screening platform for pharmacokinetic profiling of compound libraries in early drug development. Anal Chim Acta 2021; 1142: 157–168.
69. Kulkarni GT, Sethi N, Awasthi R, et al. Development of ocular delivery system for glaucoma therapy using natural hydrogel as film forming agent and release modifier. Polym Med 2016; 46: 25–33.
70. Sun J, Zhou Z. A novel ocular delivery of brinzolamide based on gellan gum: in vitro and in vivo evaluation. Drug Des Devel Ther 2018; 12: 383.
71. Wang F, Bao X, Fang A, et al. Nanoliposome-encapsulated brinzolamide-hydropropyl-$β$-cyclodextrin inclusion complex: a potential therapeutic ocular drug-delivery system. Front Pharmacol 2018; 9: 91.
72. Hu X, Tan H, Hao L. Functional hydrogel contact lens for drug delivery in the application of oculopathy therapy. J Mech Behav Biomed Mater 2016; 64: 43–52.
73. DeSouza JF, Maia KN, Patr\’\icio PSDO, et al. Ocular inserts based on chitosan and brimonidine tartrate: development, characterization and biocompatibility. J Drug Deliv Sci Technol 2016; 32: 21–30.
74. Li J, Jin X, Zhang L, et al. Comparison of different chitosan lipid nanoparticles for improved ophthalmic tetrandrine delivery: formulation, characterization, pharmacokinetic and molecular dynamics simulation. J Pharm Sci 2020; 109: 3625–3635.
75. Barwal I, Kumar R, Dada T,. et al. Effect of ultra-small chitosan nanoparticles doped with brimonidine on the ultra-structure of the trabecular meshwork of glaucoma patients. Microsc Microanal 2019; 25: 1352–1366.
76. Cho IS, Park CG, Huh BK, et al. Thermosensitive hexanoyl glycol chitosan-based ocular delivery system for glaucoma therapy. Acta Biomater 2016; 39: 124–132.
77. Pakzad Y, Fathi M, Omidi Y, et al. Synthesis and characterization of timolol maleate-loaded quaternized chitosan-based thermosensitive hydrogel: a transparent topical ocular delivery system for the treatment of glaucoma. Int J Biol Macromol 2020; 159: 117–128.
78. Dubey V, Mohan P, Dangi JS,. et al. Brinzolamide loaded chitosan-pectin mucoadhesive nanocapsules for management of glaucoma: formulation, characterization and pharmacodynamic study. Int J Biol Macromol 2020; 152: 1224–1232.
79. Mittal N, Kaur G. In situ gelling ophthalmic drug delivery system: Formulation and evaluation. J Appl Polym Sci 2014; 131: 1–9.
80. Wang L, Jiang Y-Y, Lin N. Promise of latanoprost and timolol loaded combinatorial nanosheet for therapeutic applications in glaucoma. J King Saud Univ 2020; 32: 1042–1047.
81. Ilka R, Mohseni M, Kianirad M, et al. Nanogel-based natural polymers as smart carriers for the controlled delivery of timolol maleate through the cornea for glaucoma. Int J Biol Macromol 2018; 109: 955–962.
82. Afsharipour S, Pardakhty A, Kazemipour M, et al. Formulation and physicochemical characterization of magnetic nanoparticles containing brimonidine for ophthalmic drug delivery. Int Pharm Acta n.d.; 1: 103.
83. Wang F, Song Y, Huang J, et al. Lollipop-Inspired multilayered drug delivery hydrogel for dual effective, long-term, and NIR-defined glaucoma treatment. Macromol Biosci 2021; 21: 2100202.
84. Kataria P, Katara R, Sahoo PK,. et al. Dorzolamide in situ gel forming system: characterization and evaluation for glaucoma treatment. Madridge J Pharm Res 2017; 1: 13–21.
85. VNair R, Shefrin S, Suresh A, et al. Sustained release timolol maleate loaded ocusert based on biopolymer composite. Int J Biol Macromol 2018; 110: 308–317.
86. Abdou EM, Kandil SM. Formulation and evaluation of dorzolamide and timolol ocuserts. Int J Pharm Sci Res 2017; 8: 915.
87. Calles JA, Mora MJ, Onnainty R, et al. Cross-linked hyaluronan films loaded with Acetazolamide–cyclodextrin–triethanolamine complexes for glaucoma treatment. Ther Deliv 2018; 9: 205–220.
88. Srivastava N, Choudhury AR. Microbial polysaccharide-based nanoformulations for nutraceutical delivery. ACS Omega 2022; 7: 40724–40739.
89. Shelke NB, James R, Laurencin CT,. et al. Polysaccharide biomaterials for drug delivery and regenerative engineering. Polym Adv Technol 2014; 25: 448–460.
90. Mo C, Xiang L, Chen Y. Advances in injectable and self-healing polysaccharide hydrogel based on the schiff base reaction. Macromol Rapid Commun 2021; 42: 2100025.
91. Dubashynskaya N, Poshina D, Raik S, et al. Polysaccharides in ocular drug delivery. Pharmaceutics 2019; 12: 22.
92. Zhang W, Zhao Y, Xu L, et al. Superfine grinding induced amorphization and increased solubility of $α$-chitin. Carbohydr Polym 2020; 237: 116145.
93. Wang H, Zhao X, Huang Y, et al. Rapid quality control of medicine and food dual purpose plant polysaccharides by matrix assisted laser desorption/ionization mass spectrometry. Analyst 2020; 145: 2168–2175.
94. Yang J-S, Xie Y-J, He W. Research progress on chemical modification of alginate: a review. Carbohydr Polym 2011; 84: 33–39.
95. Chen J, Liu W, Liu C-M, et al. Pectin modifications: a review. Crit Rev Food Sci Nutr 2015; 55: 1684–1698.
96. Kumar MNVR, Muzzarelli R, Muzzarelli C, et al. Chitosan chemistry and pharmaceutical perspectives. Chem Rev 2004; 104: 6017–6084.
97. Kamide K, Saito M. Cellulose and cellulose derivatives: recent advances in physical chemistry. Biopolymers 2005; 83: 1–56.
98. Giavasis I, Harvey LM, McNeil B. Gellan gum. Crit Rev Biotechnol 2000; 20: 177–211.
99. Prajapati VD, Jani GK, Moradiya NG, et al. Galactomannan: a versatile biodegradable seed polysaccharide. Int J Biol Macromol 2013; 60: 83–92.
100. Khan R, Mahendhiran B, Aroulmoji V. Chemistry of hyaluronic acid and its significance in drug delivery strategies: a review. Int J Pharm Sci Res 2013; 4: 3699–3710.
101. Nayak AK, Pal D. Functionalization of tamarind gum for drug delivery. Funct Biopolym 2018; 2: 25–56.
102. Wang S, Xu F, He J, et al. Microspheres scar formation glaucoma filtration surgery area therapeutic effect—based on rapamycin-chitosan-calcium alginate sustained-release. Mater Express 2020; 10: 848–855.

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Published In

Article first published online: May 25, 2023


  1. Glaucoma
  2. polymers
  3. polysaccharides
  4. drug delivery systems
  5. formulations

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© The Author(s) 2023.
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Manuscript received: September 19, 2022
Manuscript accepted: May 5, 2023
Published online: May 25, 2023



Tanvir Ahmed
Food Engineering & Tea Technology, Shahjalal University of Science & Technology, Sylhet 3114, Bangladesh
Md. Nazmul Islam
Deaprtment of Microbiology, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
Rina Monalisa
Deaprtment of Microbiology, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
Feroz Ehsan
Department of Medicine, Aziz Fatimah Hospital, Faisalabad 38000, Pakistan
Shu-Wei Huang
Department of Orthopedics, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan


Shu-Wei Huang, Department of Orthopedics, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan. Email: [email protected]

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