In Situ Gel Polymers: A Review

Review on in situ gels

  • RAJENDRA KUMAR JADI University College of Technology, Osmania University, Hyderabad “ 500007. TS, India.
  • Vasudha Bakshi Anurag University
  • Mounika Konatham Anurag University
  • Mounika Tejaswi Gorle Anurag University
  • Mounika Kuchkuntla Anurag University
  • Yaso Deepika Mamidisetti Anurag University
  • Naveen Pathakala Anurag University
  • Priyanka Chinthakindi Kakatiya University


 In situ gelling systems have become one of the most prominent and accessible. These systems have several advantages like simple manufacturing, easy to use, improve both adherence and patient comfort by minimizing the frequency of drug administration by its unique characteristics feature of sol to gel transition. In the 'sol-gel' method, precursor goes through reactions of hydrolysis and polymerization or condensation to produce a colloidal suspension or solution. These in situ gelling systems, as they can administer in solution form, undergo gelation at the site of action. Recently, some researchers developed in situ gelling systems of liposomes, microspheres, nanoemulsions, nanospheres, etc.  This review mainly focused on the introduction, advantages, disadvantages, types of polymers, and suitable characteristics for the preparation of in situ gels.

Keywords: In situ gels, polymer, sol-gel, gelation, tansition


1. Peppas, N.A., Huang, Y., Torres-Lugo, M., Ward, J.H., Zhang, J. Physicochemical foundations and structural design of hydrogels in medicine and biology. Annu. Rev. Biomed. Eng. 2000; 2(1): 9-29.
2. Sarada, K., Firoz, S., Padmini, K. In-situ gelling system: A review. Int. J. Curr. Pharm. Rev. Res. 2014; 5: 76-90.
3. Song, Y., Wang, Y., Thakur, R., Meidan, V.M., Michniak, B. Mucosal drug delivery: membranes, methodologies, and applications. Crit. Rev. Ther. Drug. Carrier. Syst. 2004; 21(3): 89-100.
4. P Venkatesh, M., K Liladhar, P., MP Kumar, T., G Shivakumar, H. In situ gels based drug delivery systems. Curr. Drug. ther. 2011; 6(3): 213-222.
5. Das Neves, J., Bahia, M. F. Gels as vaginal drug delivery systems. Int. J. Pharm. 2006; 318(1-2): 1-4.
6. Pasparakis, G., Vamvakaki, M. Multiresponsive polymers: nano-sized assemblies, stimuli-sensitive gels and smart surfaces. Polym. Chem. 2011; 2(6): 1234-1248.
7. Figueira, R.B., Silva, C.J., Pereira, E.V. Organic–inorganic hybrid sol–gel coatings for metal corrosion protection: a review of recent progress. J. Coat. Technol. Res. 2015; 12(1): 1-35.
8. Bae, Y., Kataoka, K. Intelligent polymeric micelles from functional poly (ethylene glycol)-poly (amino acid) block copolymers. Adv. Drug. Deliv. Rev. 2009; 61(10): 768-784.
9. Mano, J.F. Stimuli?responsive polymeric systems for biomedical applications. Adv. Eng. Mater. 2008; 10(6): 515-527.
10. Roy, D., Cambre, J.N., Sumerlin, B.S. Future perspectives and recent advances in stimuli-responsive materials. Prog. Polym. Sci. 2010; 35(1-2): 278-301.
11. Mohammad, A.W., Teow, Y.H., Ang, W.L., Chung, Y.T., Oatley-Radcliffe, D.L., Hilal, N. Nanofiltration membranes review: Recent advances and future prospects. Desalination. 2015; 356: 226-254.
12. Rai, V.K., Mishra, N., Agrawal, A.K., Jain, S., Yadav, N.P. Novel drug delivery system: an immense hope for diabetics. Drug Deliv. 2016; 23(7): 2371-2390.
13. Phad, A.R., Dilip, N.T., Ganapathy, R.S. Emulgel: a comprehensive review for topical delivery of hydrophobic drugs. Asian J. Pharm. 2018; 12(2): S382-S393.
14. HB, N., Bakliwal, S.R., Pawar, S.P. In-situ gel: new trends in controlled and sustained drug delivery system. Int. J. Pharmtech. Res. 2010; 2(2): 1398-1408.
15. Kaur, P., Garg, T., Rath, G., Goyal, A.K. In situ nasal gel drug delivery: A novel approach for brain targeting through the mucosal membrane. Artif. Cells Nanomed. Biotechnol. 2016; 44(4): 1167-1176.
16. Hsiue, G.H., Chang, R.W., Wang, C.H., Lee, S.H. Development of in situ thermosensitive drug vehicles for glaucoma therapy. Biomaterials. 2003; 24(13): 2423-2430.
17. Madan, M., Bajaj, A., Lewis, S., Udupa, N., Baig, J.A. In situ forming polymeric drug delivery systems. Indian J. Pharm. Sci. 2009; 71(3): 242-251.
18. Kute, J.U., Darekar, A.B., Saudagar, R.B. In situ gel-novel approach for nasal delivery. World J. Pharm. Pharm. Sci. 2013; 3(1): 187-203.
19. Fakhari, A., Subramony, J. A. Engineered in-situ depot-forming hydrogels for intratumoral drug delivery. J. Control. Release. 2015; 220: 465-475.
20. Liu, Y., Wang, X., Liu, Y., Di, X. Thermosensitive in situ gel based on solid dispersion for rectal delivery of ibuprofen. AAPS PharmSciTech. 2018; 19(1): 338-347.
21. Harish, N.M., Prabhu, P., Charyulu, R.N., Gulzar, M.A., Subrahmanyam, E.V.S. Formulation and evaluation of in situ gels containing clotrimazole for oral candidiasis. Indian J. Pharm. Sci. 2009; 71(4): 421-427.
22. Sonowal, B., Deb, P., Dash, S. Studies on In-Situ forming thermo sensitive injectable polymeric gel for sustained drug delivery. Res. J. Pharm. Technol. 2017; 10(6): 1840-1847.
23. Prasannan, A., Tsai, H.C., Chen, Y.S., Hsiue, G.H. A thermally triggered in situ hydrogel from poly (acrylic acid-co-N-isopropylacrylamide) for controlled release of anti-glaucoma drugs. J. Mater. Chem. B. 2014; 2(14): 1988-1997.
24. Khan, S., Patil, K., Bobade, N., Yeole, P., Gaikwad, R. Formulation of intranasal mucoadhesive temperature-mediated in situ gel containing ropinirole and evaluation of brain targeting efficiency in rats. J. Drug Target. 2010; 18(3): 223-234.
25. Jeong, B., Kim, S.W., Bae, Y.H. Thermosensitive sol–gel reversible hydrogels. Adv. Drug Deliv. Rev. 2012; 64: 154-162.
26. Matyjaszewski, K., Tsarevsky, N.V. Nanostructured functional materials prepared by atom transfer radical polymerization. Nature Chem. 2009; 1(4): 276-288.
27. 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.
28. Bai, B., Zhou, J., Yin, M.A comprehensive review of polyacrylamide polymer gels for conformance control. Petroleum Exploration and Development. 2015; 42(4): 525-532.
29. Xin, C., Lihong, W., Qiuyuan, L., Hongzhuo, L. Injectable long-term control-released in situ gels of hydrochloric thiothixene for the treatment of schizophrenia: preparation, in vitro and in vivo evaluation. Int. J. Pharm. 2014; 469(1): 23-30.
30. Packhaeuser, C.B., Schnieders, J., Oster, C.G., Kissel, T. In situ forming parenteral drug delivery systems: an overview. Eur. J. Pharm. Biopharm. 2004; 58(2): 445-455.
31. Hatefi, A., Amsden, B. Biodegradable injectable in situ forming drug delivery systems. J. Control. Release. 2002; 80(1-3): 9-28.
32. Lai, S.K., Wang, Y.Y., Hanes, J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv. Drug. Deliv. Rev. 2009; 61(2): 158-171.
33. Rees, C.A., Provis, J.L., Lukey, G.C., Van Deventer, J.S. In situ ATR-FTIR study of the early stages of fly ash geopolymer gel formation. Langmuir. 2007; 23(17): 9076-9082.
34. Gong, C., et al. Biodegradable in situ gel-forming controlled drug delivery system based on thermosensitive PCL–PEG–PCL hydrogel. Part 2: Sol–gel–sol transition and drug delivery behavior. Acta Biomater. 2009; 5(9): 3358-3370.
35. Shinde, U.P., Yeon, B., Jeong, B. Recent progress of in situ formed gels for biomedical applications. Prog. Polym. Sci. 2013; 38(3-4): 672-701.
36. Mundada, A.S., Avari, J.G. In situ gelling polymers in ocular drug delivery systems: a review. Crit. Rev. Ther. Drug. Carrier. Syst. 2009; 26(1): 85-118.
37. Gluckman, P.D., Hanson, M.A., Cooper, C., Thornburg, K. Effect of in utero and early-life conditions on adult health and disease. N. Engl. J. Med. 2008; 359(1): 61-73.
38. Patil, S., Kadam, A., Bandgar, S., Patil, S. Formulation and evaluation of an in situ gel for ocular drug delivery of anticonjunctival drug. Cellul. Chem. Technol. 2015; 49(1): 35-40.
39. Saini, R., Saini, S., Singh, G., Banerjee, A., Railmajra, D. S. In situ gels-new trends in ophthalmic drug delivery systems. Int. J. Pharm. Sci. Res. 2015; 6: 386-390.
40. Mahajan, H.S., Tyagi, V.K., Patil, R.R., Dusunge, S.B. Thiolated xyloglucan: Synthesis, characterization and evaluation as mucoadhesive in situ gelling agent. Carbohydr. Polym. 2013; 91(2): 618-625.
41. Gupta, S., Samanta, M.K., Raichur, A.M. Dual-drug delivery system based on in situ gel-forming nanosuspension of forskolin to enhance antiglaucoma efficacy. AAPS Pharmscitech. 2010; 11(1): 322-335.
42. Chang, C.F., Wang, S.C., Shigeto, S. In Situ Ultralow-Frequency Raman Tracking of the Polymorphic Transformation of Crystalline 1, 1?-Binaphthyl. The Journal of Physical Chemistry C. 2014; 118(5): 2702-2709.
43. Bashir, A., Manzoor, T., Malik, L.A., Qureashi, A., Pandith, A.H. Enhanced and Selective Adsorption of Zn (II), Pb (II), Cd (II), and Hg (II) Ions by a Dumbbell-and Flower-Shaped Potato Starch Phosphate Polymer: A Combined Experimental and DFT Calculation Study. ACS omega. 2020; 5(10): 4853-4867.
44. Raizada, A., Bandari, A., Kumar, B. Polymers in drug delivery: a review. Int. J. Pharm. Pharm. Res. Dev. 2010; 2(8): 9-20.
45. Boateng, J., Okeke, O., Khan, S. Polysaccharide based formulations for mucosal drug delivery: a review. Curr Pharm Des. 2015; 21(33): 4798-4821.
46. Tinu, T.S., Litha, T., Kumar Anil, B. Polymers used in ophthalmic in situ gelling system. Int. J. Pharm. Sci. Rev. Res. 2013; 20(1): 176-183.
47. Mohanty, D., Bakshi, V., Simharaju, N., Haque, M.A., Sahoo, C.K. A review on in-situ gel: a novel drug delivery system. Int. J. Pharm. Sci. Rev. Res. 2018; 50: 175-811.
48. Reddy, K., Krishna Mohan, G., Satla, S., Gaikwad, S. Natural Polysaccharides: Versatile Excipients for controlled drug delivery systems. Asian Journal of Pharmaceutical Sciences. 2011; 6(6): 275-286.
49. Li, L., Ni, R., Shao, Y., Mao, S. Carrageenan and its applications in drug delivery. Carbohydr. Polym. 2014; 103: 1-11.
50. MacArtain, P., Jacquier, J.C., Dawson, K.A. Physical characteristics of calcium induced ?-carrageenan networks. Carbohydr. Polym. 2003; 53(4): 395-400.
51. Honarkar, H., Barikani, M. Applications of biopolymers I: chitosan. Monatshefte für Chemie-Chem. 2009; 140(12): 1403-1420.
52. Mourya, V.K., Inamdar, N.N. Trimethyl chitosan and its applications in drug delivery. J. Mater. Sci. Mater. Med. 2009; 20(5): 1057-1079.
53. Seuring, J., Agarwal, S. Polymers with upper critical solution temperature in aqueous solution. Macromol. Rapid Commun. 2012; 33(22): 1898-1920.
54. Usman, A., Zia, K.M., Zuber, M., Tabasum, S., Rehman, S., Zia, F. Chitin and chitosan based polyurethanes: A review of recent advances and prospective biomedical applications. Int. J. Biol. Macromol. 2016; 86: 630-645.
55. Ali, A., Ahmed, S. A review on chitosan and its nanocomposites in drug delivery. Int. J. Biol. Macromol. 2018; 109: 273-286.
56. Guad, R.S., Surana, S.J., Talele, G.S., Talele, M.S., Gokhale, M.S. Natural Excipients. Pragati Books Pvt. Ltd.; 2006.
57. Smelcerovic, A., Knezevic-Jugovic, Z., Petronijevic, Z. Microbial polysaccharides and their derivatives as current and prospective pharmaceuticals. Curr. Pharm. Des. 2008; 14(29): 3168-3195.
58. Izydorczyk, M., Cui, S.W., Wang, Q. Polysaccharide gums: structures, functional properties, and applications. Food Carbohydr.: Chem. Physical Propert. Applic. 2005: 293-299.
59. Coviello, T., Matricardi, P., Marianecci, C., Alhaique, F. Polysaccharide hydrogels for modified release formulations. J. Control. Release. 2007; 119(1): 5-24.
60. Gawkowska, D., Cybulska, J., Zdunek, A. Structure-related gelling of pectins and linking with other natural compounds: A review. Polym. 2018; 10(7): 762.
61. Synytsya, A., ?op??ková, J., Mat?jka, P., Machovi?, V. Fourier transforms Raman and infrared spectroscopy of pectins. Carbohydr. Polym. 2003; 54(1): 97-106.
62. Sharma, B.R., Naresh, L., Dhuldhoya, N.C., Merchant, S.U., Merchant, U.C. An overview on pectins. Times Food Process. J. 2006; 23(2): 44-51.
63. Fakhari, A., Berkland, C. Applications and emerging trends of hyaluronic acid in tissue engineering, as dermal filler and in osteoarthritis treatment. Acta Biomaterialia. 2013; 9(7): 7081-7092.
64. Schiraldi, C., La Gatta, A., De Rosa, M. Biotechnological production and application of hyaluronan. Biopolymers. 2010; 20: 387-412.
65. Fallacara, A., Manfredini, S., Durini, E., Vertuani, S. Hyaluronic acid fillers in soft tissue regeneration. Facial Plast. Surg. 2017; 33(01): 087-096.
66. Majee, S.B., Avlani, D., Biswas, G.R. Non-starch plant polysaccharides: physicochemical modifications and pharmaceutical applications. J. Appl. Pharm. Sci. 2016; 6(10): 231-241.
67. Kapoor, M., Khandal, R.K., Seshadri, G., Aggarwal, S., Kumar Khandal, R. Novel hydrocolloids: preparation and applications–a review. Int. J. Recent Res. Appl. Stud. 2013; 16(3): 432-482.
68. Kulkarni, A.D., et al. Xyloglucan: A functional biomacromolecule for drug delivery applications. Int. J. Biol. Macromol. 2017; 104: 799-812.
69. Grabovac, V., Guggi, D., Bernkop-Schnürch, A. . Comparison of the mucoadhesive properties of various polymers. Adv. Drug. Deliv. Rev. 2005; 57(11): 1713-1723.
70. Sun, X., Zhang, N. Cationic polymer optimization for efficient gene delivery. Mini Rev. Med. Chem. 2010; 10(2): 108-125.
71. Sreenivas, S.A., Pai, K.V. Thiolated chitosans: novel polymers for mucoadhesive drug delivery–a review. Trop. J. Pharm. Res. 2008; 7(3): 1077-1088.
72. Bernkop-Schnürch, A., Hornof, M., Guggi, D. . Thiolated chitosans. Eur. J. Pharm. Biopharm. 2004; 57(1): 9-17.
73. Mokhtarzadeh, A., Alibakhshi, A., Hejazi, M., Omidi, Y., Dolatabadi, J.E.N. Bacterial-derived biopolymers: advanced natural nanomaterials for drug delivery and tissue engineering. Trends Analyt. Chem. 2016; 82: 367-384.
74. Rinaudo, M. Main properties and current applications of some polysaccharides as biomaterials. Polym. Int. 2008; 57(3): 397-430.
75. Achouri, D., Alhanout, K., Piccerelle, P., Andrieu, V. Recent advances in ocular drug delivery. Drug Dev. Ind. Pharm. 2013; 39(11):1599-1617.
76. Ruel-Gariepy, E., Leroux, J.C. In situ-forming hydrogels—review of temperature-sensitive systems. Eur. J. Pharm. Biopharm. 2004; 58(2): 409-426.
77. Almeida, H., Amaral, M.H., Lobão, P., Lobo, J.M.S. In situ gelling systems: a strategy to improve the bioavailability of ophthalmic pharmaceutical formulations. Drug Discov. Today. 2014; 19(4): 400-12.
78. Bhattarai, N., Gunn, J., Zhang, M. Chitosan-based hydrogels for controlled, localized drug delivery. Adv. Drug Deliv. Rev. 2010; 62(1): 83-99.
79. Chang, C., Zhang, L. Cellulose-based hydrogels: Present status and application prospects. Carbohydr. Polym. 2011; 84(1): 40-53.
80. Gambhire, S.A.V.I.T.A., Bhalerao, K.A.R.U.N.A., Singh, S. In situ hydrogel: Different approaches to ocular drug delivery. Int. J. Pharm. Pharm. Sci. 2013; 5(2): 27-36.
81. Xu, Y., Wang, C., Tam, K.C., Li, L. Salt-assisted and salt-suppressed sol? gel transitions of methylcellulose in water. Langmuir. 2004; 20(3): 646-652.
82. Rajoria, G., Gupta, A. In-situ gelling system: a novel approach for ocular drug delivery. Amer. J. PharmTech Res. 2012; 2: 24-53.
83. Kaur, I.P., Smitha, R. Penetration enhancers and ocular bioadhesives: two new avenues for ophthalmic drug delivery. Drug Dev. Ind. Pharm. 2002; 28(4): 353-369.
84. Wagh, V.D., Inamdar, B., Samanta, M.K. Polymers used in ocular dosage form and drug delivery systems. Asian J. Pharm. 2008; 2(1): 12-17.
85. Makadia, H.K., Siegel, S.J. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polym. 2011; 3(3): 1377-1397.
86. Hines, D.J., Kaplan, D.L. . Poly (lactic-co-glycolic) acid? controlled-release systems: experimental and modeling insights. Crit. Rev. Ther. Drug. Carrier. Syst. 2013; 30(3): 257-276.
87. Tyler, B., Gullotti, D., Mangraviti, A., Utsuki, T., Brem, H. Polylactic acid (PLA) controlled delivery carriers for biomedical applications. Adv. Drug Deliv. Rev. 2016; 107: 163-175.
88. Chand, P., Gnanarajan, G., Kothiyal, P. In situ gel: A Review. Indian J. Pharm. Biol. Res. 2016; 4(2): 11-19.
89. Dhir, S., Ali Saffi, K., Kamalpuria, N., Mishra, D. An Overview of In Situ gelling system. Inter. J. Pharma Life Sci. 2016; 7(8): 5135-5156.
90. Gu, D., O’Connor, A. J., GH Qiao, G., Ladewig, K. Hydrogels with smart systems for delivery of hydrophobic drugs. Expert. Opin. Drug Deliv. 2017; 14(7): 879-895.
91. Gonzalez-Lopez, J., Alvarez-Lorenzo, C., Taboada, P., Sosnik, A., Sandez-Macho, I., Concheiro, A. Self-associative behavior and drug-solubilizing ability of poloxamine (tetronic) block copolymers. Langmuir. 2008; 24(19): 10688-10697.
92. Alvarez-Lorenzo, C., Sosnik, A., Concheiro, A. . PEO-PPO block copolymers for passive micellar targeting and overcoming multidrug resistance in cancer therapy. Curr. Drug. Targets. 2011; 12(8): 1112-1130.
93. Almeida, M., Magalhães, M., Veiga, F., Figueiras, A. Poloxamers, poloxamines and polymeric micelles: Definition, structure and therapeutic applications in cancer. J. Polym. Res. 2018; 25(1): 31.
94. Gonzalez-Gaitano, G., Ramon Isasi, J., Velaz, I., Zornoza, A. Drug carrier systems based on cyclodextrin supramolecular assemblies and polymers: present and perspectives. Curr. Pharm. Des. 2017; 23(3): 411-432.
95. Vicario-de-la-Torre, M., Forcada, J. The potential of stimuli-responsive nanogels in drug and active molecule delivery for targeted therapy. Gels. 2017; 3(2): 16.
96. Chen, S.Y., Hu, S.H., Liu, T.Y. Magnetic-responsive nanoparticles for drug delivery. Smart Materials for Drug Delivery, 2, 32-62.
97. Dhara, D., Rathna, G.V.N., Chatterji, P.R. Volume phase transition in interpenetrating networks of poly (N-isopropylacrylamide) with gelatin. Langmuir. 2000; 16(6): 2424-2429.
98. Xie, D. et al. Multistep thermosensitivity of poly (N-n-propylacrylamide)-block-poly (N-isopropylacrylamide)-block-poly (N, N-ethylmethylacrylamide) triblock terpolymers in aqueous solutions as studied by static and dynamic light scattering. Macromolecules. 2009; 42(7): 2715-2720.
3 Views | Downloads
How to Cite
JADI, R. K., Bakshi, V., Konatham, M., Gorle, M. T., Kuchkuntla, M., Mamidisetti, Y. D., Pathakala, N., & Chinthakindi, P. (2020). In Situ Gel Polymers: A Review. International Journal of Applied Pharmaceutics, 13(1). Retrieved from
Review Article(s)