Innovative niosomal in-situ gel: Elevating ocular drug delivery synergies

Neha Kandpal Rakshanda Dhuliya Neha Padiyar Abhishek Singh Shivansh Khaudiyal Yogita Ale Vikash Jakhmola Nidhi Nainwal   

Open Access   

Published:  May 24, 2024

DOI: 10.7324/JAPS.2024.191581

The eye is an intricate organ with multiple defense mechanisms and protective barriers. This organ is susceptible to infections, hereditary abnormalities, and vision impairments. Therefore, it is necessary to administer medicine to the eyes through the appropriate method. The conventional approach of ocular drug administration may be inefficient due to limited bioavailability. Targeted drug delivery systems based on nanocarriers can overcome some restrictions encountered due to the complex structure of the eye. In situ, gel-loaded niosomes may offer advantages in the field of ocular drug delivery. Niosomes, act as a promising carrier for hydrophobic and hydrophilic medicines, shielding them from fast clearance and degradation and allowing persistent release in ocular tissues. The inclusion of niosomes in the in-situ gels provides increased corneal retention, thereby ensuring enhanced medication penetration and prolonged contact time. Furthermore, niosomes are a potential choice for long-term therapy because of their ability to offer sustained drug release, lower dose frequency, and minimize systemic side effects. This article presents a detailed review of the current state of research on niosomes-loaded in-situ gel for ocular distribution, focusing on formulation techniques, characterization, toxicity, mechanisms of action, mechanisms of sol-gel transition, and prospective uses in a various ocular illness. In-depth reviews of the various corneal penetration and absorption models for the in-vitro, in-vivo, and ex-vivo research are also presented, along with a summary of the various patents and the commercial formulation of in-situ gels.

Keyword:     Ocular drug delivery niosomal-in-situ gel synergism toxicity absorption models


Kandpal N, Dhuliya R, Padiyar N, Singh A, Khaudiyal S, Ale Y, Jakhmola V, Nainwal N. Innovative niosomal in-situ gel: Elevating ocular drug delivery synergies. J Appl Pharm Sci. 2024. Online First.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HTML Full Text


1. Al-Kinani AA, Zidan G, Elsaid N, Seyfoddin A, Alani AWG, Alany RG. Ophthalmic gels: past, present and future. Adv Drug Deliv Rev. 2018;126:113-26.

2. Qiao H, Xu Z, Sun M, Fu S, Zhao F, Wang D, et al. Rebamipide liposome as an effective ocular delivery system for the management of dry eye disease. J Drug Deliv Sci Technol. 2022;75:103654.

3. Fathalla D, Fouad EA, Soliman GM. Latanoprost niosomes as a sustained release ocular delivery system for the management of glaucoma. Drug Dev Ind Pharm. 2020;46(5):806-13.

4. Ghezzi M, Ferraboschi I, Delledonne A, Pescina S, Padula C, Santi P, et al. Cyclosporine-loaded micelles for ocular delivery: investigating the penetration mechanisms. J Control Release 2022;349:744-55.

5. Dhaval M, Devani J, Parmar R, Soniwala MM, Chavda J. Formulation and optimization of microemulsion based sparfloxacin in-situ gel for ocular delivery: in vitro and ex vivo characterization. J Drug Deliv Sci Technol. 2020;55:101373.

6. Kandpal N, Ale Y, Semwal YC, Padiyar N, Jakhmola V, Farswan AS, et al. Proniosomes: a provesicular system in ocular drug delivery. J Adv Biotechnol Exp Ther. 2023;6(3):622-37.

7. Kwon S, Kim SH, Khang D, Lee JY. Potential therapeutic usage of nanomedicine for glaucoma treatment. Int J Nanomed. 2020;15:5745-65.

8. Izhar MP, Hafeez A, Kushwaha P, Simrah. Drug delivery through niosomes: a comprehensive review with therapeutic applications. J Clust Sci. 2023;34(5):2257-73.

9. Sharma A. Recent innovation in niosomes-A comprehensive review of advancements and applications. Int J Pharm Prof Res. 2023;14(3):20-34.

10. Majeed A, Khan NA. Ocular in situ gel: an overview. J Drug Deliv Ther. 2019;9(1):337-47.

11. Chaudhari P, Shetty D, Lewis SA. Recent progress in colloidal nanocarriers loaded in situ gel in ocular therapeutics. J Drug Deliv Sci Technol. 2022;71:103327.

12. Allam A, Elsabahy M, El Badry M, Eleraky NE. Betaxolol-loaded niosomes integrated within pH-sensitive in situ forming gel for management of glaucoma. Int J Pharm. 2021;598:120380.

13. Willoughby CE, Ponzin D, Ferrari S, Lobo A, Landau K, Omidi Y. Anatomy and physiology of the human eye: effects of mucopolysaccharidoses disease on structure and function-a review. Clin Exp Ophthalmol. 2010;38(SUPPL. 1):2-11.

14. Wilson CG. Back of the eye anatomy and physiology: impact on product development. AAPS Adv Pharm Sci Ser. 2021;37:67-92.

15. Diwan P, Jangde R, Khunte S, Bhardwaj H, Suresh PK, Diwan P, et al. Ocular Drug Delivery System: Barrier for Drug Permeation, Method to Overcome Barrier. Drug Development Life Cycle. 2022.

16. Verma A, Tiwari A, Saraf S, Panda PK, Jain A, Jain SK. Emerging potential of niosomes in ocular delivery. Expert Opin Drug Deliv. 2021;18(1):55-71.

17. Durak S, Rad ME, Yetisgin AA, Sutova HE, Kutlu O, Cetinel S, et al. Niosomal drug delivery systems for ocular disease-recent advances and future prospects. Nanomaterials (Basel). 2020;10(6):1-29.

18. Marianecci C, Di Marzio L, Rinaldi F, Celia C, Paolino D, Alhaique F, et al. Niosomes from 80s to present: the state of the art. Adv Colloid Interface Sci. 2014;205:187-206.

19. Dehaghi MH, Haeri A, Keshvari H, Abbasian Z, Dadashzadeh S. Dorzolamide loaded niosomal vesicles: comparison of passive and remote loading methods. Iran J Pharm Res. 2017;16(2):413.

20. Fritze A, Hens F, Kimpfler A, Schubert R, Peschka-Süss R. Remote loading of doxorubicin into liposomes driven by a transmembrane phosphate gradient. Biochim Biophys Acta. 2006;1758(10):1633-40.

21. Rajera R, Nagpal K, Singh SK, Mishra DN. Niosomes: a controlled and novel drug delivery system. Biol Pharm Bull. 2011;34(7):945-53.

22. Destruel PL, Zeng N, Seguin J, Douat S, Rosa F, Brignole-Baudouin F, et al. Novel in situ gelling ophthalmic drug delivery system based on gellan gum and hydroxyethylcellulose: innovative rheological characterization, in vitro and in vivo evidence of a sustained precorneal retention time. Int J Pharm. 2020;574:118734.

23. Anbarasan B, Thanka J. Optimization and evaluation of temperature triggered in situ hydrogels for an effective treatment of ophthalmic preparations-a perlustration. Int J Pharm Sci Rev Res. 2018;50(2):34-9.

24. Saraf S, Ajazuddin AA, Khan J, Giri TK, Tripathi DK, et al. Advancement in stimuli triggered in situ gelling delivery for local and systemic route. Expert Opin Drug Deliv. 2012;9(12):1573-92.

25. Ward MA, Georgiou TK. Thermoresponsive gels based on ABA triblock copolymers: Does the asymmetry matter? J Polym Sci A Polym Chem. 2013;51(13):2850-9.

26. Almeida H, Amaral MH, Lobão P, Lobo JMS. In situ gelling systems: a strategy to improve the bioavailability of ophthalmic pharmaceutical formulations. Drug Discov Today. 2014;19(4):400-12.

27. Wei G, Xu H, Ding PT, Li SM, Zheng JM. Thermosetting gels with modulated gelation temperature for ophthalmic use: the rheological and gamma scintigraphic studies. J Control Release. 2002;83(1):65-74.

28. Pandey M, Choudhury H, Aziz ABA, Bhattamisra SK, Gorain B, Su JST, et al. Potential of stimuli-responsive in situ gel system for sustained ocular drug delivery: recent progress and contemporary research. Polymers. 2021;13(8):1340.

29. Elmotasem H, Awad GEA. A stepwise optimization strategy to formulate in situ gelling formulations comprising fluconazole-hydroxypropyl-beta-cyclodextrin complex loaded niosomal vesicles and Eudragit nanoparticles for enhanced antifungal activity and prolonged ocular delivery. Asian J Pharm Sci. 2020;15(5):617-36.

30. Gugleva V, Titeva S, Ermenlieva N, Tsibranska S, Tcholakova S, Rangelov S, et al. Development and evaluation of doxycycline niosomal thermoresponsive in situ gel for ophthalmic delivery. Int J Pharm. 2020;591.

31. Hemant K, Mukesh G, Rakesh G. pH Sensitive in situ ocular gel: a review. 2014.

32. Garge LV, Saudagar R. Ophthalmic pH sensitive in-situ gel: a review. J Drug Deliv Ther. 2019;9(2-s):682-9.

33. Suresh C, Abhishek S, Chand S. pH sensitive in situ ocular gel: a review. J Pharm Sci Biosci Res. 2016;6(5):684-94.

34. Zafar A, Alsaidan OA, Imam SS, Yasir M, Alharbi KS, Khalid M. Formulation and evaluation of moxifloxacin loaded bilosomes in-situ gel: optimization to antibacterial evaluation. Gels. 2022;8(7):418.

35. Wu Y, Liu Y, Li X, Kebebe D, Zhang B, Ren J, et al. Research progress of in-situ gelling ophthalmic drug delivery system. Asian J Pharm Sci. 2019;14(1):1-15.

36. Gupta H, Velpandian T, Jain S. Ion- and pH-activated novel in-situ gel system for sustained ocular drug delivery. J Drug Target. 2010;18(7):499-505.

37. Salunke SR, Patil SB. Ion activated in situ gel of gellan gum containing salbutamol sulphate for nasal administration. Int J Biol Macromol. 2016;87:41-7.

38. Balasubramaniam J, Pandit JK. Ion-activated in situ gelling systems for sustained ophthalmic delivery of ciprofloxacin hydrochloride. Drug Deliv. 2003;10(3):185-91.

39. Destruel PL, Zeng N, Brignole-Baudouin F, Douat S, Seguin J, Olivier E, et al. In situ gelling ophthalmic drug delivery system for the optimization of diagnostic and preoperative mydriasis: in vitro drug release, cytotoxicity and mydriasis pharmacodynamics. Pharmaceutics. 2020;12(4):360.

40. Padmasri B, Nagaraju R, Prasanth D. A comprehensive review on in situ gels. Int J Appl Pharm. 2020;12(6):24-33.

41. Clogston J, Rathman J, Tomasko D, Walker H, Caffrey M. Phase behavior of a monoacylglycerol: (Myverol 18-99K)/water system. Chem Phys Lipids. 2000;107(2):191-220.

42. Phaechamud T, Setthajindalert O. Antimicrobial in-situ forming gels based on bleached shellac and different solvents. J Drug Deliv Sci Technol. 2018;46:285-93.

43. Hassan RM, Khairou KS, Awad AM. New aspects to physicochemical properties of polymer gels in particularly the coordination biopolymeric metal-alginate ionotropic hydrogels. Polym Gels Synth Charact. 2018;275-354.

44. Patel LD, Shastri DH, Patel LD. A novel alternative to ocular drug delivery system: hydrogel. Int J Pharm Res. 2010;2(1):1-13. Available from:

45. Hasanji FM, Patel AK, Patel VM. In-situ gel: popular novel sustained release technique. Int J Pharm Res Appl.7:601.

46. Ahmad W, Singh A, Jaiswal KK, Gupta P. Green synthesis of photocatalytic TiO2 nanoparticles for potential application in photochemical degradation of ornidazole. J Inorg Organomet Polym Mater. 2021;31(2):614-23.

47. Meshram S, Thorat S. Review article ocular in situ gels: development, evaluation and advancements. Sch Acad J Pharm. 2015;4(7):340-46.

48. Shaikh MAJ, Alharbi KS, Almalki WH, Imam SS, Albratty M, Meraya AM, et al. Sodium alginate based drug delivery in management of breast cancer. Carbohydr Polym. 2022;292:119689.

49. Bashir R. An in sight into novel drug delivery system: in situ gels. Cellmed Orthocell Med Pharm Assoc. 2021;1-7.

50. Pande S. Liposomes for drug delivery: review of vesicular composition, factors affecting drug release and drug loading in liposomes. Artif Cells Nanomed Biotechnol. 2023;51(1):428-40.

51. Sana SS, Kumbhakar DV, Pasha A, Pawar SC, Grace AN, Singh RP, et al. Crotalaria verrucosa leaf extract mediated synthesis of zinc oxide nanoparticles: assessment of antimicrobial and anticancer activity. Molecules. 2020;25(21):4896.

52. Alyami H, Abdelaziz K, Dahmash EZ, Iyire A. Nonionic surfactant vesicles (niosomes) for ocular drug delivery: development, evaluation and toxicological profiling. J Drug Deliv Sci Technol. 2020;60:102069.

53. Dave V, Paliwal S. A novel approach to formulation factor of aceclofenac eye drops efficiency evaluation based on physicochemical characteristics of in vitro and in vivo permeation. Saudi Pharm J. 2014;22(3):240-5.

54. Han H, Li S, Xu M, Zhong Y, Fan W, Xu J, et al. Polymer- and lipid-based nanocarriers for ocular drug delivery: current status and future perspectives. Adv Drug Deliv Rev. 2023;196:114770.

55. Ana R da, Fonseca J, Karczewski J, Silva AM, Zieli?ska A, Souto EB. Lipid-based nanoparticulate systems for the ocular delivery of bioactives with anti-inflammatory properties. Int J Mol Sci. 2022;23(20):12102.

56. Patel D. Niosome drug delivery system: basics, advantage, disadvantage, applications. Gandhinagar, India: SIPS; 2020.

57. Sharma D, Ali AAE, Aate JR. Niosomes as novel drug delivery system: review article. Pharmatutor. 2018;6(3):58.

58. 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.

59. Kattar A, Quelle-Regaldie A, Sánchez L, Concheiro A, Alvarez-Lorenzo C. Formulation and characterization of epalrestat-loaded polysorbate 60 cationic niosomes for ocular delivery. Pharmaceutics. 2023;15(4):1247.

60. Bhardwaj P, Tripathi P, Gupta R, Pandey S. Niosomes: a review on niosomal research in the last decade. J Drug Deliv Sci Technol. 2020;56:101581.

61. Durak S, Rad ME, Yetisgin AA, Sutova HE, Kutlu O, Cetinel S, et al. Niosomal drug delivery systems for ocular disease-recent advances and future prospects. Nanomaterials. 2020;10(6):1191.

62. Allam A, El-Mokhtar MA, Elsabahy M. Vancomycin-loaded niosomes integrated within pH-sensitive in-situ forming gel for treatment of ocular infections while minimizing drug irritation. J Pharm Pharmacol. 2019;71(8):1209-21.

63. Pitorre M, Gondé H, Haury C, Messous M, Poilane J, Boudaud D, et al. Recent advances in nanocarrier-loaded gels: Which drug delivery technologies against which diseases? J Control Release. 2017;266:140-55.

64. Nowroozi F, Almasi A, Javidi J, Haeri A, Dadashzadeh S. effect of surfactant type, cholesterol content and various downsizing methods on the particle size of niosomes. Iran J Pharm Res. 2018;17(Suppl2):1.

65. El-Laithy HM, Shoukry O, Mahran LG. Novel sugar esters proniosomes for transdermal delivery of vinpocetine: preclinical and clinical studies. Eur J Pharm Biopharm. 2011;77(1):43-55.

66. Žiniauskait? A, C?pla V, Jelinskas T, Eimont R, Ul?inas A, Aldonyt? R, et al. Introducing an efficient in vitro cornea mimetic model for testing drug permeability. Sci. 2021;3(3):30.

67. Biswal S, Murthy PN, Sahu J, Sahoo P, Amir F. Vesicles of non-ionic surfactants (niosomes) and drug delivery potential. Int J Pharm Sci Nanotechnol. 2008;1(1):1-8.

68. Kaur D, Kumar S. Niosomes: present scenario and future aspects. J Drug Deliv Ther. 2018;8(5):35-43.

69. Chandu VP, Arunachalam A, Jeganath S, Yamini K, Tharangini K, Chaitanya G. Niosomes: a novel drug delivery system. Int J Novel Trends Pharm Sci. 2012;2(1):25-31.

70. Ramana Reddy KV, Reddy V, Ramana Reddy KV. Factors affecting in formation of niosomes. Indo Am J Pharm Res. 2014;2014(04):4.

71. Mokhtar M, Sammour OA, Hammad MA, Megrab NA. Effect of some formulation parameters on flurbiprofen encapsulation and release rates of niosomes prepared from proniosomes. Int J Pharm. 2008;361(1-2):104-11.

72. Yadav JD, Kulkarni PR, Vaidya KA, Shelke GT. Niosomes: a review. J Pharm Res. 2011;4(3):632-6.

73. Shreedevi HM, Adlin J, Nesalin J, Mani TT. Development and evaluation of stavudine niosome by ether injection method. Int J Pharma Sci Res. 2016;7(1):38-46.

74. Rao AA, Arvapalli S, Rao GSNK, Malothu N, Bandaru NR. Design and evaluation of acyclovir niosomes. Res J Pharm Technol. 2021;14(8):4185-8.

75. Sharma R, Dua JS, Prasad DN, Kaushal S, Puri A. Formulation and evaluation of clindamycin phosphate niosomes by using reverse phase evaporation method. J Drug Deliv Ther. 2019;9(3-s):515-23.

76. Paradkar MU, Parmar M. Formulation development and evaluation of Natamycin niosomal in-situ gel for ophthalmic drug delivery. J Drug Deliv Sci Technol. 2017;39:113-22.

77. Wada AM, Chanana A, Singh RP. A review on niosomes in ocular drug delivery system (ODDS). Int J Pharm Res Appl. 2022;7(6):2023-44.

78. Patel VP, Pande V V, P. V. K. Design, Development and Evaluation of Dexamethasone Sodium Phosphate Niosomal in-situ Gel for Visual Medication Conveyance. International Journal of Pharmaceutical Sciences and Nanotechnology. 2018;11(5):4274-4279.

79. Bharath S, Karuppaiah A, Siram K, Hariharan S, Santhanam R, Veintramuthu S. Development and evaluation of a pH triggered in situ ocular gel of brimonidine tartrate. J. Res. Pharm. 2020;24:416-24.

80. Kumar BS, Krishna R, Lakshmi PS, Vasudev DT, Nair SC. Formulation and evaluation of niosomal suspension of cefixime. Asian J Pharm Clin Res. 2017;10(5):194-201.

81. Article O, Acharya A, Kumar K, Gulzar Ahmed M, Paudel S. A novel approach to increase the bioavailability of candesartan cilexetil by proniosomal gel formulation: in-vitro and in-vivo evaluation. Int J Pharm Pharm Sci. 2016;8(1):241-46.

82. Souza SD', Keck CM. A review of in vitro drug release test methods for nano-sized dosage forms. Adv Pharm. 2014;2014:1-2.

83. Kim Y, Park EJ, Kim TW, Na DH. Recent progress in drug release testing methods of biopolymeric particulate system. Pharmaceutics. 2021;13(8):1313.

84. More A, Ambekar AW. Development and characterization of nanoemulsion gel for topical drug delivery of nabumetone. Int J Pharm Pharm Res. 2016;7(3):126-57.

85. Kar M, Chourasiya Y, Maheshwari R, Tekade RK. Current developments in excipient science: Implication of quantitative selection of each excipient in product development. Basic fundamentals of drug delivery. Cambridge, MA: Academic Press; 2018. pp 29-83.

86. Schafer KA, Bolon B. Special senses-ear. Fundamentals of toxicologic pathology, 3rd ed. Cambridge, MA: Academic Press; 2017. pp 729-47.

87. Lee M, Hwang JH, Lim KM. Alternatives to in vivo draize rabbit eye and skin irritation tests with a focus on 3D reconstructed human cornea-like epithelium and epidermis models. Toxicol Res. 2017;33(3):191.

88. Aboali FA, Habib DA, Elbedaiwy HM, Farid RM. Curcumin-loaded proniosomal gel as a biofreindly alternative for treatment of ocular inflammation: in-vitro and in-vivo assessment. Int J Pharm. 2020;589.

89. Dantas MGB, Reis SAGB, Damasceno CMD, Rolim LA, Rolim-Neto PJ, Carvalho FO, et al. Development and evaluation of stability of a gel formulation containing the monoterpene borneol. Sci World J. 2016;2016:7394685

90. Agha OA, Girgis GNS, El-Sokkary MMA, Soliman OAEA. Spanlastic-laden in situ gel as a promising approach for ocular delivery of Levofloxacin: in-vitro characterization, microbiological assessment, corneal permeability and in-vivo study. Int J Pharm X. 2023;6:100201.

91. Ibrahim SS. The role of surface active agents in ophthalmic drug delivery: a comprehensive review. J Pharm Sci. 2019;108(6):1923-33.

92. Roguet R, Dossou KG, Rougier A. Prediction of eye irritation potential of surfactants using the SIRC-NRU cytotoxicity test. Alternat Lab Animals. 1992;20(3):451-56;

93. Sonia TA, Sharma CP. Lipids and inorganic nanoparticles in oral insulin delivery. Oral Delivery of Insulin. Amsterdam, The Netherlands: Elsevier; 2014. pp 219-56.

94. Jahan K, Balzer S, Mosto P. Toxicity of nonionic surfactants. WIT Trans Ecol Environ. 2008;110:281.

95. Abdelkader H, Ismail S, Hussein A, Wu Z, Al-Kassas R, Alany RG. Conjunctival and corneal tolerability assessment of ocular naltrexone niosomes and their ingredients on the hen's egg chorioallantoic membrane and excised bovine cornea models. Int J Pharm. 2012;432(1-2):1-10.

96. Agarwal P, Rupenthal ID. In vitro and ex vivo corneal penetration and absorption models. Drug Deliv Transl Res. 2016;6(6):634-47.

97. Ahuja M, Sharma SK, Majumdar DK. In vitro corneal permeation of diclofenac from oil drops. Yakugaku Zasshi. 2007;127(10):1739-45.

98. Bíró T, Bocsik A, Dukovski BJ, Gróf I, Lovri? J, Csóka I, et al. New approach in ocular drug delivery: in vitro and ex vivo investigation of cyclodextrin-containing, mucoadhesive eye drop formulations. Drug Design Dev Ther 2021; 15: 351-60.

99. Tho I, Škalko-Basnet N. Cell-based in vitro models for vaginal permeability studies. Concepts and Models for Drug Permeability Studies: Cell and Tissue based in Vitro Culture Models. Cambridge, MA: Woodhead Publishing; 2015. pp 115-28.

100. Veit JGS, Birru B, Singh R, Arrigali EM, Serban MA. An in vitro model for characterization of drug permeability across the tympanic membrane. Pharmaceuticals. 2022;15(9):1114.

101. Scholz M, Lin JEC, Lee VHL, Keipert S. Pilocarpine permeability across ocular tissues and cell cultures: influence of formulation parameters. J Ocul Pharmacol Ther. 2002;18(5):455-68.

102. Becker U, Ehrhardt C, Schneider M, Muys L, Gross D, Eschmann K, et al. A comparative evaluation of corneal epithelial cell cultures for assessing ocular permeability. Altern Lab Anim. 2008;36(1):33-44.

103. De Hoon I, Boukherroub R, De Smedt SC, Szunerits S, Sauvage F. In vitro and ex vivo models for assessing drug permeation across the Cornea. Mol Pharm. 2023;20(7):3298-319.

104. Abdelbary GA, Amin MM, Zakaria MY. Ocular ketoconazole-loaded proniosomal gels: formulation, ex vivo corneal permeation and in vivo studies. Drug Deliv. 2017;24(1):309-19.

105. Rodriguez-Aller M, Guillarme D, El Sanharawi M, Behar-Cohen F, Veuthey JL, Gurny R. In vivo distribution and ex vivo permeation of cyclosporine A prodrug aqueous formulations for ocular application. J Control Release. 2013;170(1):153-9.

106. Weng Y, Liu J, Jin S, Guo W, Liang X, Hu Z. Nanotechnology-based strategies for treatment of ocular disease. Acta Pharm Sin B. 2017;7(3):281-91.

107. Bruschi ML, Borghi-Pangoni FB, Junqueira MV, de Souza Ferreira SB. Nanostructured therapeutic systems with bioadhesive and thermoresponsive properties. Nanostruct Novel Ther Syn Charact Appl. 2017;313-42.

108. Nishinari K, Takemasa M, Zhang H, Takahashi R. Storage plant polysaccharides: xyloglucans, galactomannans, glucomannans. Comprehen Glycosci Chem Syst Biol. 2007;2-4:613-52.

109. Kumar VV, Chetty CM, Reddy YD, Ugandar RE, Gladiola BD. Formulation and in vitro characterization of ocular in situ gels of valcyclovir. J Pharm Sci Res. 2019;11(8):2974-9.

110. Khare P, Chogale MM, Kakade P, Patravale VB. Gellan gum-based in situ gelling ophthalmic nanosuspension of Posaconazole. Drug Deliv Transl Res. 2022;12(12):2920-35.

111. Liu Y, Liu J, Zhang X, Zhang R, Huang Y, Wu C. In situ gelling gelrite/alginate formulations as vehicles for ophthalmic drug delivery. AAPS PharmSciTech. 2010;11(2):610.

112. Kurniawansyah IS, Rusdiana T, Sopyan I, Ramoko H, Wahab HA, Subarnas A. In situ ophthalmic gel forming systems of poloxamer 407 and hydroxypropyl methyl cellulose mixtures for sustained ocular delivery of chloramphenicole: optimization study by factorial design. Heliyon. 2020;6(11):e05365.

113. Abbas MN, Khan SA, Sadozai SK, Khalil IA, Anter A, El Fouly M, et al. Nanoparticles loaded thermoresponsive in situ gel for ocular antibiotic delivery against bacterial keratitis. Polymers (Basel). 2022;14(6).

114. 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.

115. Datta S, Bhowmik R, Nath R, Chakraborty R, Chakraborty A. Formulation and evaluation of a nanoparticle laden in situ gel system for enhancing the ocular delivery of ciprofloxacin. Int J Pharm Sci Rev Res. 2021;70(2):156-63.

116. Kesarla R, Tank T, Vora PA, Shah T, Parmar S, Omri A. Preparation and evaluation of nanoparticles loaded ophthalmic in situ gel. Drug Deliv. 2016;23(7):2363-70.

117. Londhe VY, Sharma S. Formulation, characterization, optimization and in-vivo evaluation of methazolamide liposomal in-situ gel for treating glaucoma. J Drug Deliv Sci Technol. 2022;67:102951.

118. Shukr MH, Ismail S, El-Hossary GG, El-Shazly AH. Design and evaluation of mucoadhesive in situ liposomal gel for sustained ocular delivery of travoprost using two steps factorial design. J Drug Deliv Sci Technol. 2021;61:102333.

119. Yu S, Wang QM, Wang X, Liu D, Zhang W, Ye T, et al. Liposome incorporated ion sensitive in situ gels for opthalmic delivery of timolol maleate. Int J Pharm. 2015;480(1-2):128-36.

120. Khallaf AM, El-Moslemany RM, Ahmed MF, Morsi MH, Khalafallah NM. Exploring a novel fasudil-phospholipid complex formulated as liposomal thermosensitive in situ gel for glaucoma. Int J Nanomed. 2022;17:163-81.

121. Morsi N, Ibrahim M, Refai H, El Sorogy H. Nanoemulsion-based electrolyte triggered in situ gel for ocular delivery of acetazolamide. Eur J Pharm Sci. 2017;104:302-14.

122. Mahboobian MM, Mohammadi M, Mansouri Z. Development of thermosensitive in situ gel nanoemulsions for ocular delivery of acyclovir. J Drug Deliv Sci Technol. 2020;55:101400.

123. Bhalerao H, Koteshwara K, Chandran S. Design, optimisation and evaluation of in situ gelling nanoemulsion formulations of brinzolamide. Drug Deliv Transl Res. 2020;10(2):529-47.

124. 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.

125. Youssef AAA, Dudhipala N, Majumdar S. Dual drug loaded lipid nanocarrier formulations for topical ocular applications. Int J Nanomedicine. 2022;17:2283-99.

126. Wadetwar RN, Agrawal AR, Kanojiya PS. In situ gel containing Bimatoprost solid lipid nanoparticles for ocular delivery: in-vitro and ex-vivo evaluation. J Drug Deliv Sci Technol. 2020;56:101575.

127. Tatke A, Dudhipala N, Janga KY, Balguri SP, Avula B, Jablonski MM, et al. In situ gel of triamcinolone acetonide-loaded solid lipid nanoparticles for improved topical ocular delivery: tear kinetics and ocular disposition studies. Nanomaterials. 2018;9(1):33.

128. Chaudhari PD, Desai US. Formulation and evaluation of niosomal in situ gel of prednisolone sodium phosphate for ocular drug delivery. Int J Appl Pharm. 2019;11(2):97-116.

129. Aggarwal D, Kaur IP. Improved pharmacodynamics of timolol maleate from a mucoadhesive niosomal ophthalmic drug delivery system. Int J Pharm. 2005;290(1-2):155-9.

130. 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(1):888-99.

131. Zhu L, Ao J, Li P. A novel in situ gel base of deacetylase gellan gum for sustained ophthalmic drug delivery of ketotifen: in vitro and in vivo evaluation. Drug Des Devel Ther. 2015;9:3943-9.

132. Sathyavathi V, Hasansathali AA, Ilavarasan R, Sangeetha A. Formulation and evaluation of niosomal in situ gel ocular delivery system of brimonidine tartrate. Int J Life Sci Pharma Res. 2012;2(1):82-95.

133. Gugleva V, Michailova V, Mihaylova R, Momekov G, Zaharieva MM, Najdenski H, et al. Formulation and evaluation of hybrid niosomal in situ gel for intravesical co-delivery of curcumin and gentamicin sulfate. Pharmaceutics. 2022;14(4):747.

134. Bisht M, Kanyal R, Bhardwaj M, Kumar A. Development and characterization of flurbiprofen loaded niosomal in-situ gel for ophthalmic drug delivery system. Annal Romanian Soc Cell Biol. 2021;25(6):20635-55. Available from:

135. Gupta P, Yadav KS. Formulation and evaluation of brinzolamide encapsulated niosomal in-situ gel for sustained reduction of IOP in rabbits. J Drug Deliv Sci Technol. 2022;67:103004.

136. Tegtmeyer S, Papantoniou I, Müller-Goymann CC. Reconstruction of an in vitro cornea and its use for drug permeation studies from different formulations containing pilocarpine hydrochloride. Eur J Pharm Biopharm. 2001;51(2):119-25.

137. Reichl S, Bednarz J, Müller-Goymann CC. Human corneal equivalent as cell culture model for in vitro drug permeation studies. Br J Ophthalmol. 2004;88(4):560-5.

138. Saarinen-Savolainen P, Järvinen T, Araki-Sasaki K, Watanabe H, Urtti A. Evaluation of cytotoxicity of various ophthalmic drugs, eye drop excipients and cyclodextrins in an immortalized human corneal epithelial cell line. Pharm Res. 1998;15(8):1275-80.

139. Van Der Bijl P, Engelbrecht AH, Van Eyk AD, Meyer D. Comparative permeability of human and rabbit corneas to cyclosporin and tritiated water. J Ocul Pharmacol Ther. 2002;18(5):419-27.

140. Van Der Bijl P, Van Eyk AD, Seifart HI, Meyer D. In vitro transcorneal penetration of metronidazole and its potential use as adjunct therapy in Acanthamoeba keratitis. Cornea. 2004;23(4):386-9.

141. Loch C, Zakelj S, Kristl A, Nagel S, Guthoff R, Weitschies W, et al. Determination of permeability coefficients of ophthalmic drugs through different layers of porcine, rabbit and bovine eyes. Eur J Pharm Sci. 2012;47(1):131-8.

142. Remington LA. Cornea and Sclera. Clinical anatomy and physiology of the visual system. New York, NY: Elsevier Health Sciences; 2012. pp 10-39.

143. Pawar PK, Majumdar DK. Effect of formulation factors on in vitro permeation of moxifloxacin from aqueous drops through excised goat, sheep, and buffalo corneas. AAPS Pharm Sci Tech. 2006;7(1):E89-E94.

144. Xia E, Furr RB. United States (12) Patent Application Publication (10) Pub. 2002;(43).

145. Lin. Date of Patent. 2003;511(45):9-10.

146. Xia E et al. Reversible gelling system for ocular drug delivery. 2004;1-6.

147. Adeyeye M et al. Ophthalmic drug delivery system of estradiol or other estrogen for prevention of cataracts. United States Patent Application Publication. 2011.

148. Mohan N. In-situ gel forming solution for ocular drug delivery-oogle Patents. WIPO (PCT). 2011. Available from: Accessed 23 September 2023.

149. Banerjee et al. Nanoparticulate in-situ gels of TPGS, gellan and PVA as vitreous humor substitutes. United states patent. 2013.

150. Verma S, Nainwal N, Kikon NY, Ali A, Jakhmola V. Hopes and hurdles of nanogels in the treatment of ocular diseases. J Appl Pharm Sci. 2024;14,(2):001-012.

151. Ahmed TA, Aljaeid BM. A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole. Int J Nanomed. 2017;12:1863-75.

Article Metrics
106 Views 12 Downloads 118 Total



Related Search

By author names