In situ Gel: A Promising Ocular Drug Delivery System
Abstract
The eye is a vital organ, faces challenges in drug delivery with traditional ophthalmic formulations due to the rapid loss of medications before reaching the cornea. This review explores novel drug delivery systems for ocular administration, emphasizing innovative dosage forms, i.e., in situ gels. This system aims to prolong drug contact time in the eyes, overcoming bioavailability issues associated with conventional delivery methods. The article further delves into in situ gelation approaches, highlighting pH-triggered, temperature-dependent, and ion-activated systems. It explores the use of excipients like polymers and solubilizing agents in the preparation of in-situ gels. The frequently used polymers and their applications in ocular drug delivery are detailed. Studies on the incorporation of nanoparticles in this gelling system for ocular drug delivery. Methodologies for evaluating in situ gels, including pH determination, rheological studies, drug content analysis, in vitro gelation, accelerated stability studies, and FTIR analysis, are presented. The advantages & applications of in situ gels are discussed, along with its limitations. The review concludes by emphasizing the benefits of novel ocular drug delivery systems, particularly in situ ophthalmic systems, which offer controlled and sustained drug release, and the future perspective of in situ gel. These advancements hold promise for more effective therapeutic outcomes in the field of ocular drug delivery.
Keywords:
In situ gel, Polymer, Nanoparticles, Ocular barriers, Ocular drug delivery, Ophthalmic drug delivery
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References
Al-Kinani, A. A., Zidan, G., Elsaid, N., Seyfoddin, A., Alani, A. W., & Alany, R. G. (2018). Ophthalmic gels: Past, present and future. Advanced drug delivery reviews, 126, 113-126. https://doi.org/10.1016/j.addr.2017.12.017
Al-mahallawi, A. M., Ahmed, D., Hassan, M., & El-Setouhy, D. A. (2021). Enhanced ocular delivery of clotrimazole via loading into mucoadhesive microemulsion system: In vitro characterization and in vivo assessment. Journal of Drug Delivery Science and Technology, 64, 102561. https://doi.org/10.1016/j.jddst.2021.102561
Almeida, H., Amaral, M. H., Lobão, P., & Lobo, J. M. S. (2014). In situ gelling systems: a strategy to improve the bioavailability of ophthalmic pharmaceutical formulations. Drug discovery today, 19(4), 400-412. https://doi.org/10.1016/j.drudis.2013.10.001
Baig, M. S., Ahmad, A., Pathan, R. R., and Mishra, R. K. (2024). Precision Nanomedicine with Bio-Inspired Nanosystems: Recent Trends and Challenges in Mesenchymal Stem Cells Membrane-Coated Bioengineered Nanocarriers in Targeted Nanotherapeutics. J. Xenobiotics 14, 827–872. https://doi.org/10.3390/jox14030047.
Balu, A., Johnson, T., Sundara, R., & Seetharaman, S. (2020). Optimization and Evaluation of Temperature Triggered in situ Gel Formulation using Design of Experiments (DoE) and HET-CAM Test. J. Nanomed, 3, 1031. http://meddocsonline.org/
Boddu, S. H., Bonam, S. P., & Jung, R. (2015). Development and characterization of a ricinoleic acid poloxamer gel system for transdermal eyelid delivery. Drug development and industrial pharmacy, 41(4), 605-612.. https://doi.org/10.3109/03639045.2014.886696
Ceulemans, J., & Ludwig, A. (2002). Optimisation of carbomer viscous eye drops: an in vitro experimental design approach using rheological techniques. European Journal of Pharmaceutics and Biopharmaceutics, 54(1), 41-50. https://doi.org/10.1016/S0939-6411(02)00036-X
Chaudhari, P., Shetty, D., & Lewis, S. A. (2022). Recent progress in colloidal nanocarriers loaded in situ gel in ocular therapeutics. Journal of Drug Delivery Science and Technology, 71, 103327. https://doi.org/10.1016/j.jddst.2022.103327
Chowhan, A., & Giri, T. K. (2020). Polysaccharide as renewable responsive biopolymer for in situ gel in the delivery of drug through ocular route. International journal of biological macromolecules, 150, 559-572. https://doi.org/10.1016/j.ijbiomac.2020.02.097
Dewan, M., Adhikari, A., Jana, R., & Chattopadhyay, D. (2023). Development, evaluation and recent progress of ocular in situ gelling drug delivery vehicle based on poloxamer 407. Journal of Drug Delivery Science and Technology, 104885. https://doi.org/10.1016/j.jddst.2023.104885
Ding, X., Yu, Y., Li, W., & Zhao, Y. (2023). In situ 3D-bioprinting MoS2 accelerated gelling hydrogel scaffold for promoting chronic diabetic wound healing. Matter, 6(3), 1000-1014. https://doi.org/10.1016/j.matt.2023.01.001
Esteruelas, G., Halbaut, L., Garcia-Torra, V., Espina, M., Cano, A., Ettcheto, M., ... & Sanchez-Lopez, E. (2022). Development and optimization of Riluzole-loaded biodegradable nanoparticles incorporated in a mucoadhesive in situ gel for the posterior eye segment. International Journal of Pharmaceutics, 612, 121379. https://doi.org/10.1016/j.ijpharm.2021.121379
Fang, G., Yang, X., Wang, Q., Zhang, A., & Tang, B. (2021). Hydrogels-based ophthalmic drug delivery systems for treatment of ocular diseases. Materials Science and Engineering: C, 127, 112212.https://doi.org/10.1016/j.msec.2021.112212
Ganguly, S., & Dash, A. K. (2004). A novel in situ gel for sustained drug delivery and targeting. International journal of pharmaceutics, 276(1-2), 83-92. https://doi.org/10.1016/j.ijpharm.2004.02.014
Geetha, A., Chakka, P., & Thirumalesh, G. S. B. (2023). Formulation and evaluation of pH-induced in situ gels of a non-steroidal anti- inflammatory drug ( NSAID ) “ Ketorolac .”71(8), 88–97.
Gupta, H., Velpandian, T., & Jain, S. (2010). Ion-and pH-activated novel in situ gel system for sustained ocular drug delivery. Journal of drug targeting, 18(7), 499-505. https://doi.org/10.3109/10611860903508788
Kaur, I. P., Singh, M., & Kanwar, M. (2000). Formulation and evaluation of ophthalmic preparations of acetazolamide. International journal of pharmaceutics, 199(2), 119-127. https://doi.org/10.1016/S0378-5173(00)00359-8
Konatham, M. O. U. N. I. K. A., Gorle, M. T., Pathakala, N. A. V. E. E. N., Bakshi, V. A. S. U. D. H. A., Mamidisetti, Y. D., Chinthakindi, P. R. I. Y. A. N. K. A., & Jadi, R. K. (2021). In situ gel polymers: A review. Int J App Pharm, 13(1), 86-90.https://doi.org/10.22159/ijap.2021v13i1.39504
Laddha, U. D., & Kshirsagar, S. J. (2021). Formulation of nanoparticles loaded in situ gel for treatment of dry eye disease: In vitro, ex vivo and in vivo evidences. Journal of Drug Delivery Science and Technology, 61, 102112. https://doi.org/10.1016/j.jddst.2020.102112
Lin, Q., Si, Y., Zhou, F., Hao, W., Zhang, P., Jiang, P., & Cha, R. (2023). Advances in polysaccharides for probiotic delivery: Properties, methods, and applications. Carbohydrate Polymers, 121414. https://doi.org/10.1016/j.carbpol.2023.121414
Lynch, C. R., Kondiah, P. P., Choonara, Y. E., Du Toit, L. C., Ally, N., & Pillay, V. (2020). Hydrogel biomaterials for application in ocular drug delivery. Frontiers in bioengineering and biotechnology, 8, 228. https://doi.org/10.3389/fbioe.2020.00228
Makwana, S. B., Patel, V. A., & Parmar, S. J. (2016). Development and characterization of in situ gel for ophthalmic formulation containing ciprofloxacin hydrochloride. Results in pharma sciences, 6, 1-6. https://doi.org/10.1016/j.rinphs.2015.06.001
Mandal, S., Thimmasetty, M. K., Prabhushankar, G. L., & Geetha, M. S. (2012). Formulation and evaluation of an in situ gel-forming ophthalmic formulation of moxifloxacin hydrochloride. International journal of pharmaceutical investigation, 2(2), 78. https://doi.org/10.4103/2230-973x.100042
Moghimipour, E., Salimi, A., & Yousefvand, T. (2017). Preparation and evaluation of celecoxib nanoemulsion for ocular drug delivery. Asian Journal of Pharmaceutics, 11(3), S543–S550.
Mohanty, D., Bakshi, V., Simharaju, N., Haque, M. A., & Sahoo, C. K. (2018). A review on in situ gel: a novel drug delivery system. Int. J. Pharm. Sci. Rev. Res, 50(1), 175-181.
Nirmal, H. B., Bakliwal, S. R., & Pawar, S. P. (2010). In situ gel: New trends in controlled and sustained drug delivery system. International Journal of PharmTech Research, 2(2), 1398–1408
Priya, S., Srividya, G., Chandra, N. S., Singh, P. P., Saha, R. N., Sathe, P., ... & Singhvi, G. (2023). Loteprednol etabonate loaded lyotropic liquid crystalline nanoparticles in situ ophthalmic gel: Qbd driven optimization and in-vitro, ex-vivo evidence of sustained precorneal residence time. Journal of Drug Delivery Science and Technology, 89, 105081. https://doi.org/10.1016/j.jddst.2023.105081
Rohaľová, S., Wolaschka, T., Balážová, Ľ., Paulovičová, K., Tóthová, J., Pavloková, S., ... & Gajdziok, J. (2024). Formulation optimization and evaluation of oromucosal in situ gel loaded with silver nanoparticles prepared by green biosynthesis. European Journal of Pharmaceutical Sciences, 193, 106683. https://doi.org/10.1016/j.ejps.2023.106683
Sacco, P., Furlani, F., De Marzo, G., Marsich, E., Paoletti, S., & Donati, I. (2018). Concepts for developing physical gels of chitosan and of chitosan derivatives. Gels, 4(3), 67. https://doi.org/10.3390/gels4030067
Senarat, S., Lwin, W. W., Mahadlek, J., & Phaechamud, T. (2021). Doxycycline hyclate-loaded in situ forming gels composed from bleached shellac, Ethocel, and Eudragit RS for periodontal pocket delivery. Saudi pharmaceutical journal, 29(3), 252-263. https://doi.org/10.1016/j.jsps.2021.01.009
Shah, M. R., Imran, M., & Ullah, S. (2022). Overcoming ocular barriers through nanocarrier-based drug delivery systems. In M. R. Shah, M. Imran, & S. Ullah (Eds.), Nanocarriers for Organ-Specific and Localized Drug Delivery (pp. 225–244). Elsevier. https://doi.org/https://doi.org/10.1016/B978-0-12-821093-2.00009-8
Sheshala, R., Ming, N. J., Kok, Y. Y., Singh, T. R. R., & Dua, K. (2019). Formulation and characterization of pH induced in situ gels containing sulfacetamide sodium for ocular drug delivery: A combination of Carbopol®/HPMC polymer. Indian Journal of Pharmaceutical Education and Research, 53(4), 654–662. https://doi.org/10.5530/ijper.53.4.127
Shukr, M. H., Ismail, S., El-Hossary, G. G., & El-Shazly, A. H. (2021). Design and evaluation of mucoadhesive in situ liposomal gel for sustained ocular delivery of travoprost using two steps factorial design. Journal of drug delivery science and technology, 61, 102333. https://doi.org/10.1016/j.jddst.2021.102333
Soliman, K. A., Ullah, K., Shah, A., Jones, D. S., & Singh, T. R. (2019). Poloxamer-based in situ gelling thermoresponsive systems for ocular drug delivery applications. Drug Discovery Today, 24(8), 1575-1586. https://doi.org/10.1016/j.drudis.2019.05.036
Sravya, B., Ruchitha, M., Soujanya, K., Raveena, N., Hussaini, S. A., & Jayaram, M. (2022). Formulation and Evaluation of a pH Induced In Situ Occular Gelling System of Ketorolac. 1(2), 56–63.
Srividya, B. J. R. M., Cardoza, R. M., & Amin, P. D. (2001). Sustained ophthalmic delivery of ofloxacin from a pH triggered in situ gelling system. Journal of controlled release, 73(2-3), 205-211. https://doi.org/10.1016/S0168-3659(01)00279-6
Chavda, D., Thakkar, V., Soni, T., & Gandhi, T. (2016). Formulation and in vitro-in vivo evaluations of Timolol maleate viscous eye drops for the treatment of glaucoma. European Journal of Biomedical, 3(9), 573-585.
Uppuluri, C. T., Ravi, P. R., & Dalvi, A. V. (2021). Design and evaluation of thermo-responsive nasal in situ gelling system dispersed with piribedil loaded lecithin-chitosan hybrid nanoparticles for improved brain availability. Neuropharmacology, 201, 108832. https://doi.org/10.1016/j.neuropharm.2021.108832
Wei, W., Li, H., Yin, C., & Tang, F. (2020). Research progress in the application of in situ hydrogel system in tumor treatment. Drug Delivery, 27(1), 460-468. https://doi.org/10.1080/10717544.2020.1739171
Wiwattanapatapee, R., Klabklay, K., Raksajit, N., Siripruekpong, W., Leelakanok, N., & Petchsomrit, A. (2023). The development of an in situ biopolymer-based floating gel for the oral delivery of metformin hydrochloride. Heliyon, 9(4). https://doi.org/10.1016/j.heliyon.2023.e14796
Young, M. (2008). Heroic indolence: Realism and the politics of time in Raffaëlli's Absinthe Drinkers. The Art Bulletin, 90(2), 235-259. https://doi.org/10.1080/00043079.2008.10786392
Youssef, A., Dudhipala, N., & Majumdar, S. (2020). Ciprofloxacin loaded nanostructured lipid carriers incorporated into in situ gels to improve management of bacterial endophthalmitis. Pharmaceutics, 12(6), 572.https://doi.org/10.3390/pharmaceutics12060572
Yu, S., Wang, Q. M., Wang, X., Liu, D., Zhang, W., Ye, T., ... & Pan, W. (2015). Liposome incorporated ion sensitive in situ gels for opthalmic delivery of timolol maleate. International journal of pharmaceutics, 480(1-2), 128-136. https://doi.org/10.1016/j.ijpharm.2015.01.032
Al-mahallawi, A. M., Ahmed, D., Hassan, M., & El-Setouhy, D. A. (2021). Enhanced ocular delivery of clotrimazole via loading into mucoadhesive microemulsion system: In vitro characterization and in vivo assessment. Journal of Drug Delivery Science and Technology, 64, 102561. https://doi.org/10.1016/j.jddst.2021.102561
Almeida, H., Amaral, M. H., Lobão, P., & Lobo, J. M. S. (2014). In situ gelling systems: a strategy to improve the bioavailability of ophthalmic pharmaceutical formulations. Drug discovery today, 19(4), 400-412. https://doi.org/10.1016/j.drudis.2013.10.001
Baig, M. S., Ahmad, A., Pathan, R. R., and Mishra, R. K. (2024). Precision Nanomedicine with Bio-Inspired Nanosystems: Recent Trends and Challenges in Mesenchymal Stem Cells Membrane-Coated Bioengineered Nanocarriers in Targeted Nanotherapeutics. J. Xenobiotics 14, 827–872. https://doi.org/10.3390/jox14030047.
Balu, A., Johnson, T., Sundara, R., & Seetharaman, S. (2020). Optimization and Evaluation of Temperature Triggered in situ Gel Formulation using Design of Experiments (DoE) and HET-CAM Test. J. Nanomed, 3, 1031. http://meddocsonline.org/
Boddu, S. H., Bonam, S. P., & Jung, R. (2015). Development and characterization of a ricinoleic acid poloxamer gel system for transdermal eyelid delivery. Drug development and industrial pharmacy, 41(4), 605-612.. https://doi.org/10.3109/03639045.2014.886696
Ceulemans, J., & Ludwig, A. (2002). Optimisation of carbomer viscous eye drops: an in vitro experimental design approach using rheological techniques. European Journal of Pharmaceutics and Biopharmaceutics, 54(1), 41-50. https://doi.org/10.1016/S0939-6411(02)00036-X
Chaudhari, P., Shetty, D., & Lewis, S. A. (2022). Recent progress in colloidal nanocarriers loaded in situ gel in ocular therapeutics. Journal of Drug Delivery Science and Technology, 71, 103327. https://doi.org/10.1016/j.jddst.2022.103327
Chowhan, A., & Giri, T. K. (2020). Polysaccharide as renewable responsive biopolymer for in situ gel in the delivery of drug through ocular route. International journal of biological macromolecules, 150, 559-572. https://doi.org/10.1016/j.ijbiomac.2020.02.097
Dewan, M., Adhikari, A., Jana, R., & Chattopadhyay, D. (2023). Development, evaluation and recent progress of ocular in situ gelling drug delivery vehicle based on poloxamer 407. Journal of Drug Delivery Science and Technology, 104885. https://doi.org/10.1016/j.jddst.2023.104885
Ding, X., Yu, Y., Li, W., & Zhao, Y. (2023). In situ 3D-bioprinting MoS2 accelerated gelling hydrogel scaffold for promoting chronic diabetic wound healing. Matter, 6(3), 1000-1014. https://doi.org/10.1016/j.matt.2023.01.001
Esteruelas, G., Halbaut, L., Garcia-Torra, V., Espina, M., Cano, A., Ettcheto, M., ... & Sanchez-Lopez, E. (2022). Development and optimization of Riluzole-loaded biodegradable nanoparticles incorporated in a mucoadhesive in situ gel for the posterior eye segment. International Journal of Pharmaceutics, 612, 121379. https://doi.org/10.1016/j.ijpharm.2021.121379
Fang, G., Yang, X., Wang, Q., Zhang, A., & Tang, B. (2021). Hydrogels-based ophthalmic drug delivery systems for treatment of ocular diseases. Materials Science and Engineering: C, 127, 112212.https://doi.org/10.1016/j.msec.2021.112212
Ganguly, S., & Dash, A. K. (2004). A novel in situ gel for sustained drug delivery and targeting. International journal of pharmaceutics, 276(1-2), 83-92. https://doi.org/10.1016/j.ijpharm.2004.02.014
Geetha, A., Chakka, P., & Thirumalesh, G. S. B. (2023). Formulation and evaluation of pH-induced in situ gels of a non-steroidal anti- inflammatory drug ( NSAID ) “ Ketorolac .”71(8), 88–97.
Gupta, H., Velpandian, T., & Jain, S. (2010). Ion-and pH-activated novel in situ gel system for sustained ocular drug delivery. Journal of drug targeting, 18(7), 499-505. https://doi.org/10.3109/10611860903508788
Kaur, I. P., Singh, M., & Kanwar, M. (2000). Formulation and evaluation of ophthalmic preparations of acetazolamide. International journal of pharmaceutics, 199(2), 119-127. https://doi.org/10.1016/S0378-5173(00)00359-8
Konatham, M. O. U. N. I. K. A., Gorle, M. T., Pathakala, N. A. V. E. E. N., Bakshi, V. A. S. U. D. H. A., Mamidisetti, Y. D., Chinthakindi, P. R. I. Y. A. N. K. A., & Jadi, R. K. (2021). In situ gel polymers: A review. Int J App Pharm, 13(1), 86-90.https://doi.org/10.22159/ijap.2021v13i1.39504
Laddha, U. D., & Kshirsagar, S. J. (2021). Formulation of nanoparticles loaded in situ gel for treatment of dry eye disease: In vitro, ex vivo and in vivo evidences. Journal of Drug Delivery Science and Technology, 61, 102112. https://doi.org/10.1016/j.jddst.2020.102112
Lin, Q., Si, Y., Zhou, F., Hao, W., Zhang, P., Jiang, P., & Cha, R. (2023). Advances in polysaccharides for probiotic delivery: Properties, methods, and applications. Carbohydrate Polymers, 121414. https://doi.org/10.1016/j.carbpol.2023.121414
Lynch, C. R., Kondiah, P. P., Choonara, Y. E., Du Toit, L. C., Ally, N., & Pillay, V. (2020). Hydrogel biomaterials for application in ocular drug delivery. Frontiers in bioengineering and biotechnology, 8, 228. https://doi.org/10.3389/fbioe.2020.00228
Makwana, S. B., Patel, V. A., & Parmar, S. J. (2016). Development and characterization of in situ gel for ophthalmic formulation containing ciprofloxacin hydrochloride. Results in pharma sciences, 6, 1-6. https://doi.org/10.1016/j.rinphs.2015.06.001
Mandal, S., Thimmasetty, M. K., Prabhushankar, G. L., & Geetha, M. S. (2012). Formulation and evaluation of an in situ gel-forming ophthalmic formulation of moxifloxacin hydrochloride. International journal of pharmaceutical investigation, 2(2), 78. https://doi.org/10.4103/2230-973x.100042
Moghimipour, E., Salimi, A., & Yousefvand, T. (2017). Preparation and evaluation of celecoxib nanoemulsion for ocular drug delivery. Asian Journal of Pharmaceutics, 11(3), S543–S550.
Mohanty, D., Bakshi, V., Simharaju, N., Haque, M. A., & Sahoo, C. K. (2018). A review on in situ gel: a novel drug delivery system. Int. J. Pharm. Sci. Rev. Res, 50(1), 175-181.
Nirmal, H. B., Bakliwal, S. R., & Pawar, S. P. (2010). In situ gel: New trends in controlled and sustained drug delivery system. International Journal of PharmTech Research, 2(2), 1398–1408
Priya, S., Srividya, G., Chandra, N. S., Singh, P. P., Saha, R. N., Sathe, P., ... & Singhvi, G. (2023). Loteprednol etabonate loaded lyotropic liquid crystalline nanoparticles in situ ophthalmic gel: Qbd driven optimization and in-vitro, ex-vivo evidence of sustained precorneal residence time. Journal of Drug Delivery Science and Technology, 89, 105081. https://doi.org/10.1016/j.jddst.2023.105081
Rohaľová, S., Wolaschka, T., Balážová, Ľ., Paulovičová, K., Tóthová, J., Pavloková, S., ... & Gajdziok, J. (2024). Formulation optimization and evaluation of oromucosal in situ gel loaded with silver nanoparticles prepared by green biosynthesis. European Journal of Pharmaceutical Sciences, 193, 106683. https://doi.org/10.1016/j.ejps.2023.106683
Sacco, P., Furlani, F., De Marzo, G., Marsich, E., Paoletti, S., & Donati, I. (2018). Concepts for developing physical gels of chitosan and of chitosan derivatives. Gels, 4(3), 67. https://doi.org/10.3390/gels4030067
Senarat, S., Lwin, W. W., Mahadlek, J., & Phaechamud, T. (2021). Doxycycline hyclate-loaded in situ forming gels composed from bleached shellac, Ethocel, and Eudragit RS for periodontal pocket delivery. Saudi pharmaceutical journal, 29(3), 252-263. https://doi.org/10.1016/j.jsps.2021.01.009
Shah, M. R., Imran, M., & Ullah, S. (2022). Overcoming ocular barriers through nanocarrier-based drug delivery systems. In M. R. Shah, M. Imran, & S. Ullah (Eds.), Nanocarriers for Organ-Specific and Localized Drug Delivery (pp. 225–244). Elsevier. https://doi.org/https://doi.org/10.1016/B978-0-12-821093-2.00009-8
Sheshala, R., Ming, N. J., Kok, Y. Y., Singh, T. R. R., & Dua, K. (2019). Formulation and characterization of pH induced in situ gels containing sulfacetamide sodium for ocular drug delivery: A combination of Carbopol®/HPMC polymer. Indian Journal of Pharmaceutical Education and Research, 53(4), 654–662. https://doi.org/10.5530/ijper.53.4.127
Shukr, M. H., Ismail, S., El-Hossary, G. G., & El-Shazly, A. H. (2021). Design and evaluation of mucoadhesive in situ liposomal gel for sustained ocular delivery of travoprost using two steps factorial design. Journal of drug delivery science and technology, 61, 102333. https://doi.org/10.1016/j.jddst.2021.102333
Soliman, K. A., Ullah, K., Shah, A., Jones, D. S., & Singh, T. R. (2019). Poloxamer-based in situ gelling thermoresponsive systems for ocular drug delivery applications. Drug Discovery Today, 24(8), 1575-1586. https://doi.org/10.1016/j.drudis.2019.05.036
Sravya, B., Ruchitha, M., Soujanya, K., Raveena, N., Hussaini, S. A., & Jayaram, M. (2022). Formulation and Evaluation of a pH Induced In Situ Occular Gelling System of Ketorolac. 1(2), 56–63.
Srividya, B. J. R. M., Cardoza, R. M., & Amin, P. D. (2001). Sustained ophthalmic delivery of ofloxacin from a pH triggered in situ gelling system. Journal of controlled release, 73(2-3), 205-211. https://doi.org/10.1016/S0168-3659(01)00279-6
Chavda, D., Thakkar, V., Soni, T., & Gandhi, T. (2016). Formulation and in vitro-in vivo evaluations of Timolol maleate viscous eye drops for the treatment of glaucoma. European Journal of Biomedical, 3(9), 573-585.
Uppuluri, C. T., Ravi, P. R., & Dalvi, A. V. (2021). Design and evaluation of thermo-responsive nasal in situ gelling system dispersed with piribedil loaded lecithin-chitosan hybrid nanoparticles for improved brain availability. Neuropharmacology, 201, 108832. https://doi.org/10.1016/j.neuropharm.2021.108832
Wei, W., Li, H., Yin, C., & Tang, F. (2020). Research progress in the application of in situ hydrogel system in tumor treatment. Drug Delivery, 27(1), 460-468. https://doi.org/10.1080/10717544.2020.1739171
Wiwattanapatapee, R., Klabklay, K., Raksajit, N., Siripruekpong, W., Leelakanok, N., & Petchsomrit, A. (2023). The development of an in situ biopolymer-based floating gel for the oral delivery of metformin hydrochloride. Heliyon, 9(4). https://doi.org/10.1016/j.heliyon.2023.e14796
Young, M. (2008). Heroic indolence: Realism and the politics of time in Raffaëlli's Absinthe Drinkers. The Art Bulletin, 90(2), 235-259. https://doi.org/10.1080/00043079.2008.10786392
Youssef, A., Dudhipala, N., & Majumdar, S. (2020). Ciprofloxacin loaded nanostructured lipid carriers incorporated into in situ gels to improve management of bacterial endophthalmitis. Pharmaceutics, 12(6), 572.https://doi.org/10.3390/pharmaceutics12060572
Yu, S., Wang, Q. M., Wang, X., Liu, D., Zhang, W., Ye, T., ... & Pan, W. (2015). Liposome incorporated ion sensitive in situ gels for opthalmic delivery of timolol maleate. International journal of pharmaceutics, 480(1-2), 128-136. https://doi.org/10.1016/j.ijpharm.2015.01.032
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How to Cite
Khan, J., Khan, A., Khan, A., Khan, D., Shaikh, A. H., & Baig, M. S. (2024). In situ Gel: A Promising Ocular Drug Delivery System. International Journal of Advancement in Life Sciences Research, 7(3), 65-77. https://doi.org/https://doi.org/10.31632/ijalsr.2024.v07i03.006
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