Natural Polymers Used In In Situgelling Systems
Abstract
In situ gelling systems have recently garnered immense interest as an innovative method for increasing drug retention time, bioavailability, and efficacy. However, among the materials used in in situ gel formulations, natural polymers have emerged as an innovative substitute over synthetic polymers because of their superior biocompatibility, biodegradability, and safety profile. This review emphasizes on the use of various natural polymers in in situ gelling systems in terms of their gelation mechanism, physicochemical characterization, and pharmaceutical properties. Case studies from recently published reports illustrating the use of such polymers have also been included. The choice of natural polymers like alginate, chitosan, pectin, gellan gum, guar gum, and xanthan gum shows potential because they have high mucoadhesive properties, toxicity, and environmental sustainability. These biomaterials can be used in all routes of drug delivery. They also have less immunogenic potential, lack chronic toxicity, are potentially compliant with increased patient safety, and are readily biodegradable in comparison with synthetic polymers. The case studies included in this review highlight the use of natural polymer-based in situ gels for achieving targeted and sustained drug release with enhanced durability and therapeutic effects. In situ gelling systems containing natural polymers constitute a safer, more environmentally friendly, and highly efficient method over synthetic polymer-based in situ gels.
Downloads
References
Vigani B, Rossi S, Sandri G, Bonferoni MC, Caramella CM, Ferrari F. Recent advances in the development of in situ gelling drug delivery systems for non-parenteral administration routes. Pharmaceutics. 2020;12(9):859.
Ezike TC, Okpala US, Onoja UL, Nwike CP, Ezeako EC, Okpara OJ, Okoroafor CC, Eze SC, Kalu OL, Odoh EC, Nwadike UG. Advances in drug delivery systems, challenges, and future directions. Heliyon. 2023;9(6): e17488.
Hedaya MA. Routes of drug administration. InPharmaceutics 2024 Jan 1 (pp. 537-554). Academic Press.
Al Shoyaib A, Archie SR, Karamyan VT. Intraperitoneal route of drug administration: should it be used in experimental animal studies? Pharmaceutical research. 2020;37(1):12.
Schweitzer SO, Lu ZJ. Pharmaceutical economics and policy: perspectives, promises, and problems. Oxford University Press; 2018.
Kolawole OM, Cook MT. In situ gelling drug delivery systems for topical drug delivery. European Journal of Pharmaceutics and Biopharmaceutics. 2023;184:36-49.
HB N, Bakliwal S, Pawar S. In-situ gel: new trends in controlled and sustained drug delivery system. International Journal of PharmTech Research. 2010;2(2):1398-408.
Jain KK. An overview of drug delivery systems. Drug delivery systems. 2019:1-54.
Ajazuddin, Alexander A, Khan J, Giri TK, Tripathi DK, Saraf S, Saraf S. Advancement in stimuli triggered in situ gelling delivery for local and systemic route. Expert opinion on drug delivery. 2012;9(12):1573-92.
Kouchak M. In situ gelling systems for drug delivery. Jundishapur J Nat Pharm Prod. 2014; 9(3):e20126.
Pandey M, Choudhury H, binti Abd Aziz A, Bhattamisra SK, Gorain B, Su JS, Tan CL, Chin WY, Yip KY. Potential of stimuli-responsive in situ gel system for sustained ocular drug delivery: Recent progress and contemporary research. Polymers. 2021;13(8):1340.
Geethalakshmia A, Karkib R, Sagib P, Jhac SK, Pb VD. Temperature triggered in situ gelling system for betaxolol in glaucoma. Journal of Applied Pharmaceutical Science. 2013;3(2):153-9.
Srividya BJ, Cardoza RM, Amin PD. Sustained ophthalmic delivery of ofloxacin from a pH triggered in situ gelling system. Journal of controlled release. 2001;73(2-3):205-11.
Rupenthal ID, Green CR, Alany RG. Comparison of ion-activated in situ gelling systems for ocular drug delivery. Part 1: physicochemical characterisation and in vitro release. International journal of pharmaceutics. 2011;411(1-2):69-77.
Vossoughi S. Profile modification using in situ gelation technology—a review. Journal of Petroleum Science and Engineering. 2000;26(1-4):199-209.
Muhr AH, Blanshard JM. Diffusion in gels. Polymer. 1982;23(7):1012-26.
Li Z, Lu F, Liu Y. A review of the mechanism, properties, and applications of hydrogels prepared by enzymatic cross-linking. Journal of Agricultural and Food Chemistry. 2023;71(27):10238-49.
Almeida H, Amaral MH, Lobão P, Lobo JM. In situ gelling systems: a strategy to improve the bioavailability of ophthalmic pharmaceutical formulations. Drug discovery today. 2014;19(4):400-12.
Kurniawansyah IS, Rusdiana T, Sopyan I, Desy Arya IF, Wahab HA, Nurzanah D. Comparative study of in situ gel formulation based on the physico-chemical aspect: Systematic review. Gels. 2023;9(8):645.
Lanier OL, Manfre MG, Bailey C, Liu Z, Sparks Z, Kulkarni S, Chauhan A. Review of approaches for increasing ophthalmic bioavailability for eye drop formulations. Aaps Pharmscitech. 2021;22(3):107.
Shrewsbury SB. The upper nasal space: Option for systemic drug delivery, mucosal vaccines and “Nose-to-Brain”. Pharmaceutics. 2023;15(6):1720.
Deshpande AA, Rhodes CT, Shah NH, Malick AW. Controlled-release drug delivery systems for prolonged gastric residence: an overview. Drug development and industrial pharmacy. 1996;22(6):531-9.
Hearnden V, Sankar V, Hull K, Juras DV, Greenberg M, Kerr AR, Lockhart PB, Patton LL, Porter S, Thornhill MH. New developments and opportunities in oral mucosal drug delivery for local and systemic disease. Advanced drug delivery reviews. 2012;64(1):16-28.
Vigani B, Faccendini A, Rossi S, Sandri G, Bonferoni MC, Grisoli P, Ferrari F. Development of a mucoadhesive in situ gelling formulation for the delivery of Lactobacillus gasseri into vaginal cavity. Pharmaceutics. 2019;11(10):511.
Hatefi A, Amsden B. Biodegradable injectable in situ forming drug delivery systems. Journal of controlled release. 2002;80(1-3):9-28.
Gowda BJ, Ahmed MG, Husain A. Transferosomal in situ gel administered through umbilical skin tissues for improved systemic bioavailability of drugs: A novel strategy to replace conventional transdermal route. Medical Hypotheses. 2022;161:110805.
Singh S, Singh S, Khandelwal V, Singh AP, Sachan K, Singh PK. Novel Approach and Recent Advancement In-Situ Gel as Smart Carriers for Controlled Drug Delivery via Ophthalmic Route. Drug Delivery Letters. 2025; 15(4): 427-48.
Danks AE, Hall SR, Schnepp ZJ. The evolution of ‘sol–gel’chemistry as a technique for materials synthesis. Materials Horizons. 2016;3(2):91-112.
Satchanska G, Davidova S, Petrov PD. Natural and Synthetic Polymers for Biomedical and Environmental Applications. Polymers (Basel). 2024;16(8):1159.
Lee CH, Moturi V, Lee Y. Thixotropic property in pharmaceutical formulations. Journal of controlled release. 2009;136(2):88-98.
Shaikh R, Singh TR, Garland MJ, Woolfson AD, Donnelly RF. Mucoadhesive drug delivery systems. Journal of pharmacy and Bioallied Sciences. 2011;3(1):89-100.
Satchanska G, Davidova S, Petrov PD. Natural and synthetic polymers for biomedical and environmental applications. Polymers. 2024;16(8):1159.
Bhowmik M, Kumari P, Sarkar G, Bain MK, Bhowmick B, Mollick MM, Mondal D, Maity D, Rana D, Bhattacharjee D, Chattopadhyay D. Effect of xanthan gum and guar gum on in situ gelling ophthalmic drug delivery system based on poloxamer-407. International journal of biological macromolecules. 2013;62:117-23.
Mondal A, Barai S, Bera H, Patel T, Sahoo NG, Begum D, Ghosh B. Ferulic acid-g-tamarind gum/guar gum-based in situ gel-forming powders as wound dressings. International Journal of Biological Macromolecules. 2024;277:134382.
Kumar JR, Muralidharan S, Dhanaraj SA. Development and in vitro evaluation of guar gum-based fluconazole in situ gel for oral thrush. Journal of Pharmaceutical Sciences and Research. 2012;4(12):2009.
Aranaz I, Alcántara AR, Civera MC, Arias C, Elorza B, Heras Caballero A, Acosta N. Chitosan: An overview of its properties and applications. Polymers. 2021;13(19):3256.
Barati M, Samani SM, Jahromi LP, Ashrafi H, Azadi A. Controlled-release in-situ gel forming formulation of tramadol containing chitosan-based pro-nanogels. International Journal of Biological Macromolecules. 2018;118:1449-54.
Varshosaz J, Tabbakhian M, Salmani Z. Designing of a thermosensitive chitosan/poloxamer in situ gel for ocular delivery of ciprofloxacin. Open Drug Deliv. J. 2008;2(1):61-70.
Therkelsen GH. Carrageenan. InIndustrial gums 1993 Jan 1 (pp. 145-180). Academic Press.
Vigani B, Rossi S, Gentile M, Sandri G, Bonferoni MC, Cavalloro V, Martino E, Collina S, Ferrari F. Development of a mucoadhesive and an in situ gelling formulation based on κ-carrageenan for application on oral mucosa and esophagus walls. II. Loading of a bioactive hydroalcoholic extract. Marine drugs. 2019;17(3):153.
Rawat PS, Ravi PR, Mir SI, Khan MS, Kathuria H, Katnapally P, Bhatnagar U. Design, characterization and pharmacokinetic–pharmacodynamic evaluation of poloxamer and kappa-carrageenan-based dual-responsive in situ gel of nebivolol for treatment of open-angle glaucoma. Pharmaceutics. 2023;15(2):405.
Rolin C. Pectin. InIndustrial gums 1993 Jan 1 (pp. 257-293). Academic Press.
Itoh K, Hatakeyama T, Shimoyama T, Miyazaki S, D’Emanuele A, Attwood D. In situ gelling formulation based on methylcellulose/pectin system for oral-sustained drug delivery to dysphagic patients. Drug development and industrial pharmacy. 2011;37(7):790-7.
Moreira HR, Munarin F, Gentilini R, Visai L, Granja PL, Tanzi MC, Petrini P. Injectable pectin hydrogels produced by internal gelation: pH dependence of gelling and rheological properties. Carbohydrate polymers. 2014;103:339-47.
Urlacher B, Dalbe B. Xanthan gum. In Thickening and gelling agents for food 1997 (pp. 202-226). Boston, MA: Springer US.
Vemuri S, Abraham S, Azamthulla M, Furtado S, Bharath S. Development of in situ gels of nano calcium oxide for healing of burns. Wound Medicine. 2020;28:100177.
Xue D, Sethi R. Viscoelastic gels of guar and xanthan gum mixtures provide long-term stabilization of iron micro-and nanoparticles. Journal of nanoparticle research. 2012;14(11):1239.
Thakur S, Sharma B, Verma A, Chaudhary J, Tamulevicius S, Thakur VK. Recent progress in sodium alginate based sustainable hydrogels for environmental applications. Journal of cleaner production. 2018;198:143-59.
Noreen S, Ghumman SA, Batool F, Ijaz B, Basharat M, Noureen S, Kausar T, Iqbal S. Terminalia arjuna gum/alginate in situ gel system with prolonged retention time for ophthalmic drug delivery. International journal of biological macromolecules. 2020;152:1056-67.
Allam AA, Eleraky NE, Diab NH, Elsabahy M, Mohamed SA, Abdel-Ghaffar HS, Hassan NA, Shouman SA, Omran MM, Hassan SB, Eissa NG. Development of sedative dexmedetomidine sublingual in situ gels: in vitro and in vivo evaluations. Pharmaceutics. 2022;14(2):220.
Sworn G, Stouby L. Gellan gum. InHandbook of hydrocolloids 2021 Jan 1 (pp. 855-885). Woodhead Publishing.
Rao MR, Shelar SU, Yunusi AA. Controlled release floating oral in situ gel of itopride hydrochloride using pH sensitive polymer. Int. J. Pharm. Pharm. Sci. 2014;6:338-43.
Nanaware S, Nayak A, Jain AP. Development and characterization of nasal insitu gel of sumatriptan and naproxen for effective treatment of migraine using 32 factorial designs. Journal of Advanced Scientific Research. 2021;12(02):273-83.
Gao D, Lv J, Lee PS. Natural polymer in soft electronics: opportunities, challenges, and future prospects. Advanced Materials. 2022;34(25):2105020.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Chogale Manasi, Nisha Gautam, Mhatre Snehal, Yadav Rakesh, Mhatre Netra, Gaikwad Kashish
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
AUTHORS WHO PUBLISH WITH THIS JOURNAL AGREE TO THE FOLLOWING TERMS:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 Unported License. that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
. 