A REVIEW ON RECENT ADVANCES IN HYDROGELS AS DRUG DELIVERY SYSTEM

AYAM GHANEM; SONDOS AHMAD ASHOUR; RUAA M HUSSIEN

doi:10.22159/ijap.2025v17i1.51987

Authors

AYAM GHANEM Department of Applied science, Faculty of Aqaba college, Al-Balqa Applied University, P. O. Box 206, Salt-19117, Jordan https://orcid.org/0000-0002-4246-7640
SONDOS AHMAD ASHOUR Master of pharmaceutical technology, Department of Pharmacy, University of Medical Sciences and Technology, Khartoum-Sudan https://orcid.org/0000-0002-6039-9709
RUAA M HUSSIEN Master of Clinical pharmacy, Department of clinical pharmacy, University of Jordan, Amman- Jordan https://orcid.org/0009-0006-6792-8614

DOI:

https://doi.org/10.22159/ijap.2025v17i1.51987

Keywords:

Hydrogels, Networks, Hydrophilic, Drug targeting, Drug delivery, Crosslinking

Abstract

Hydrogels are hydrophilic three dimensional polymeric networks, which has the capability to absorb water or biological fluids. These polymeric network is formulated through chemical crosslinking or physical crosslinking mechanisms. Several polymers of synthetic and natural origin can be used to form hydrogels. Mechanical properties, swelling and biological properties are about the most significant hydrogels properties, that can affect their morphology and structure. Hydrogels are promising biomaterials due to their significant properties as hydrophilicity, biodegradability, biocompatibility and non-toxicity. These characteristics make hydrogels appropriate for medical and pharmaceutical application. This review discusses the types of hydrogels, their properties, mechanism of preparation and applications of hydrogels as drug delivery system.

Downloads

Download data is not yet available.

References

Ahmed EM. Hydrogel: Preparation, characterization, and applications: A review. J Adv Res. 2015 Mar;6(2):105–21.

Chamkouri H. A Review of Hydrogels, Their Properties and Applications in Medicine. Am J Biomed Sci Res. 2021 Feb 3;11:485–93.

Sánchez-Cid P, Jiménez-Rosado M, Romero A, Pérez-Puyana V. Novel Trends in Hydrogel Development for Biomedical Applications: A Review. Polymers. 2022 Jul 26;14(15).

Giordano S, Gallo E, Diaferia C, Rosa E, Carrese B, Borbone N, Scognamiglio PL, Franzese M, Oliviero G, Accardo A. Multicomponent Peptide-Based Hydrogels Containing Chemical Functional Groups as Innovative Platforms for Biotechnological Applications. Gels Basel Switz. 2023 Nov 15;9(11).

Karoyo AH, Wilson LD. A Review on the Design and Hydration Properties of Natural Polymer-Based Hydrogels. Mater Basel Switz. 2021 Feb 26;14(5).

Cao H, Duan L, Zhang Y, Cao J, Zhang K. Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity. Signal Transduct Target Ther. 2021 Dec 16;6(1):426.

Ho TC, Chang CC, Chan HP, Chung TW, Shu CW, Chuang KP, Duh TH, Yang MH, Tyan YC. Hydrogels: Properties and Applications in Biomedicine. Mol Basel Switz. 2022 May 2;27(9).

Cai MH, Chen XY, Fu LQ, Du WL, Yang X, Mou XZ, Hu PY. Design and Development of Hybrid Hydrogels for Biomedical Applications: Recent Trends in Anticancer Drug Delivery and Tissue Engineering. Front Bioeng Biotechnol. 2021;9:630943.

Catoira MC, Fusaro L, Di Francesco D, Ramella M, Boccafoschi F. Overview of natural hydrogels for regenerative medicine applications. J Mater Sci Mater Med. 2019 Oct 10;30(10):115.

Lu L, Yuan S, Wang J, Shen Y, Deng S, Xie L, Yang Q. The Formation Mechanism of Hydrogels. Curr Stem Cell Res Ther. 2018;13(7):490–6.

Peng W, Li D, Dai K, Wang Y, Song P, Li H, Tang P, Zhang Z, Li Z, Zhou Y, Zhou C. Recent progress of collagen, chitosan, alginate and other hydrogels in skin repair and wound dressing applications. Int J Biol Macromol. 2022 May 31;208:400–8.

Chen M, Wang Y, Zhang J, Peng Y, Li S, Han D, Ren S, Qin K, Li S, Gao Z. Stimuli-responsive DNA-based hydrogels for biosensing applications. J Nanobiotechnology. 2022 Jan 21;20(1):40.

Jiang Y, Wang Y, Li Q, Yu C, Chu W. Natural Polymer-based Stimuli-responsive Hydrogels. Curr Med Chem. 2020;27(16):2631–57.

Wang C, Zhang J. Recent Advances in Stimuli-Responsive DNA-Based Hydrogels. ACS Appl Bio Mater. 2022 May 16;5(5):1934–53.

Das, S., V. Kumar, R. Tiwari, L. Singh, and S. Singh. “RECENT ADVANCES IN HYDROGELS FOR BIOMEDICAL APPLICATIONS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 11, no. 11, Nov. 2018, pp. 62-68, doi:10.22159/ajpcr.2018.v11i11.27921.

Amsden B. Solute Diffusion within Hydrogels. Mechanisms and Models. Macromolecules. 1998 Nov 1;31(23):8382–95.

Ghasemiyeh P, Mohammadi-Samani S. Hydrogels as Drug Delivery Systems; Pros and Cons. Trends Pharm Sci. 2019 Mar 1;5(1):7–24.

Gerecht S, Townsend SA, Pressler H, Zhu H, Nijst CLE, Bruggeman JP, Nichol JW, Langer R. A porous photocurable elastomer for cell encapsulation and culture. Biomaterials. 2007;28(32):4826–35.

Ganji F, Vasheghani FS, Vasheghani FE. Theoretical description of hydrogel swelling: a review. 2010;

Yin L, Fei L, Cui F, Tang C, Yin C. Superporous hydrogels containing poly(acrylic acid-co-acrylamide)/O-carboxymethyl chitosan interpenetrating polymer networks. Biomaterials. 2007 Feb 1;28(6):1258–66.

Lima CSA de, Balogh TS, Varca JPRO, Varca GHC, Lugão AB, A. Camacho-Cruz L, Bucio E, Kadlubowski SS. An Updated Review of Macro, Micro, and Nanostructured Hydrogels for Biomedical and Pharmaceutical Applications. Pharmaceutics. 2020 Oct;12(10):970.

Hafezi Moghaddam R, Dadfarnia S, Shabani AMH, Moghaddam ZH, Tavakol M. Electron beam irradiation synthesis of porous and non-porous pectin based hydrogels for a tetracycline drug delivery system. Mater Sci Eng C. 2019 Sep 1;102:391–404.

Garg S, Garg A. Hydrogel: Classification, Properties, Preparation and Technical Features. Asian J Biomater Res. 2016 Sep 4;2:163–70.

Holback H, Yeo Y, Park K. 1 - Hydrogel swelling behavior and its biomedical applications. In: Rimmer S, editor. Biomedical Hydrogels [Internet]. Woodhead Publishing; 2011 [cited 2023 Sep 27]. p. 3–24. (Woodhead Publishing Series in Biomaterials). Available from: https://www.sciencedirect.com/science/article/pii/B9781845695903500011

Sornkamnerd S, Okajima MK, Kaneko T. Tough and Porous Hydrogels Prepared by Simple Lyophilization of LC Gels. ACS Omega. 2017 Aug 31;2(8):5304–14.

Luo R, Wu J, Dinh ND, Chen CH. Gradient Porous Elastic Hydrogels with Shape-Memory Property and Anisotropic Responses for Programmable Locomotion. Adv Funct Mater. 2015;25(47):7272–9.

De France KJ, Xu F, Hoare T. Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities. Adv Healthc Mater. 2018;7(1):1700927.

AM R, PRABHU S S, J D, J R, SUNDARAM S K, R M, TK V. HYDROGEL FORMULATION FROM CALOTROPIS GIGANTEA PLANT EXTRACT AGAINST FOOT ULCER CAUSING BACTERIA IN DIABETES. Asian J Pharm Clin Res. 2021 Nov. 7;14(11):96-9.

Gemeinhart RA, Park H, Park K. Pore structure of superporous hydrogels. Polym Adv Technol. 2000;11(8–12):617–25.

Thakur S, Thakur VK, Arotiba OA. History, Classification, Properties and Application of Hydrogels: An Overview. In: Thakur VK, Thakur MK, editors. Hydrogels: Recent Advances [Internet]. Singapore: Springer; 2018 [cited 2023 Sep 25]. p. 29–50. (Gels Horizons: From Science to Smart Materials). Available from: https://doi.org/10.1007/978-981-10-6077-9_2

Zhan Y, Fu W, Xing Y, Ma X, Chen C. Advances in versatile anti-swelling polymer hydrogels. Mater Sci Eng C. 2021 Aug 1;127:112208.

Peppas NA, Bures P, Leobandung W, Ichikawa H. Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm. 2000 Jul 3;50(1):27–46.

Lin CC, Metters AT. Hydrogels in controlled release formulations: Network design and mathematical modeling. Adv Drug Deliv Rev. 2006 Nov 30;58(12):1379–408.

Kim D, Park K. Swelling and mechanical properties of superporous hydrogels of poly(acrylamide-co-acrylic acid)/polyethylenimine interpenetrating polymer networks. Polymer. 2004 Jan 1;45(1):189–96.

Gemeinhart RA, Chen J, Park H, Park K. pH-sensitivity of fast responsive superporous hydrogels. J Biomater Sci Polym Ed. 2000 Jan 1;11(12):1371–80.

Huglin MB, Liu Y, Velada JoséL. Thermoreversible swelling behaviour of hydrogels based on N-isopropylacrylamide with acidic comonomers. Polymer. 1997 Nov 1;38(23):5785–91.

Brannon-Peppas L, Peppas NA. Equilibrium swelling behavior of pH-sensitive hydrogels. Chem Eng Sci. 1991 Jan 1;46(3):715–22.

Kasai D, Devi R, S Puthran A, Hamzad S, Koutavarapu R, Lee DY, Shim J. A review on hydrogels classification and recent developments in biomedical applications. Int J Polym Mater Polym Biomater. 2022 May 19;72:1–11.

Younis MK, Tareq AZ, Kamal IM. Optimization Of Swelling, Drug Loading And Release From Natural Polymer Hydrogels. IOP Conf Ser Mater Sci Eng. 2018 Dec;454(1):012017.

Ovadia M, Silverstein MS. High porosity, responsive hydrogel copolymers from emulsion templating. Polym Int. 2016;65(3):280–9.

Huang T, Xu HG, Jiao K, Zhu LP, Brown H, Wang H. A Novel Hydrogel with High Mechanical Strength: A Macromolecular Microsphere Composite Hydrogel. Adv Mater. 2007 May 15;19:1622–6.

Gong JP. Why are double network hydrogels so tough? Soft Matter. 2010 Jun 8;6(12):2583–90.

Haque MA, Kurokawa T, Kamita G, Gong JP. Lamellar Bilayers as Reversible Sacrificial Bonds To Toughen Hydrogel: Hysteresis, Self-Recovery, Fatigue Resistance, and Crack Blunting. Macromolecules. 2011 Nov 22;44(22):8916–24.

Hu J, Hiwatashi K, Kurokawa T, Liang SM, Wu ZL, Gong JP. Microgel-Reinforced Hydrogel Films with High Mechanical Strength and Their Visible Mesoscale Fracture Structure. Macromolecules. 2011 Oct 11;44(19):7775–81.

Suekama TC, Hu J, Kurokawa T, Gong JP, Gehrke SH. Double-Network Strategy Improves Fracture Properties of Chondroitin Sulfate Networks. ACS Macro Lett. 2013 Feb 19;2(2):137–40.

Chen Q, Chen H, Zhu L, Zheng J. Fundamentals of Double Network Hydrogels. J Mater Chem B. 2015 Mar 31;3.

Chen Y, Dong K, Liu Z, Xu F. Double network hydrogel with high mechanical strength: Performance, progress and future perspective. Sci China Technol Sci. 2012 Aug 1;55(8):2241–54.

Argenta DF, dos Santos TC, Campos AM, Caon T. Chapter 3 - Hydrogel Nanocomposite Systems: Physico-Chemical Characterization and Application for Drug-Delivery Systems∗∗Dedicated to Professor Claudia Maria Oliveira Simões on the occasion of her retirement. In: Mohapatra SS, Ranjan S, Dasgupta N, Mishra RK, Thomas S, editors. Nanocarriers for Drug Delivery [Internet]. Elsevier; 2019 [cited 2023 Oct 17]. p. 81–131. (Micro and Nano Technologies). Available from: https://www.sciencedirect.com/science/article/pii/B9780128140338000035

Haraguchi K, Takehisa T. Nanocomposite Hydrogels: A Unique Organic–Inorganic Network Structure with Extraordinary Mechanical, Optical, and Swelling/Deswelling Properties. Adv Mater - ADVAN MATER. 2002 Aug 16;14.

Xu K, Wang J, Xiang S, Chen Q, Yue Y, Su X, Song C, Wang P. Polyampholytes superabsorbent nanocomposites with excellent gel strength. Compos Sci Technol. 2007 Dec 1;67(15):3480–6.

Das D, Kar T, Das PK. Gel-nanocomposites: materials with promising applications. Soft Matter. 2012 Feb 2;8(8):2348–65.

Kabiri K, Omidian H, Hashemi SA, Zohuriaan-Mehr MJ. Synthesis of fast-swelling superabsorbent hydrogels: effect of crosslinker type and concentration on porosity and absorption rate. Eur Polym J. 2003 Jul 1;39(7):1341–8.

Chavda H, Patel C. Effect of crosslinker concentration on characteristics of superporous hydrogel. Int J Pharm Investig. 2011;1(1):17–21.

Kabiri K, Zohuriaan-Mehr MJ. Porous Superabsorbent Hydrogel Composites: Synthesis, Morphology and Swelling Rate. Macromol Mater Eng. 2004;289(7):653–61.

Annabi N, Mithieux SM, Boughton EA, Ruys AJ, Weiss AS, Dehghani F. Synthesis of highly porous crosslinked elastin hydrogels and their interaction with fibroblasts in vitro. Biomaterials. 2009 Sep 1;30(27):4550–7.

Pandey M, Mohd Amin MCI, Ahmad N, Abeer MM. Rapid Synthesis of Superabsorbent Smart-Swelling Bacterial Cellulose/Acrylamide-Based Hydrogels for Drug Delivery. Int J Polym Sci [Internet]. 2013 Aug 28 [cited 2023 Nov 5];2013. Available from: https://www.hindawi.com/journals/ijps/2013/905471/

Gupta NV, Shivakumar HG. Preparation and Characterization of Superporous Hydrogels as pH-Sensitive Drug Delivery System for Pantoprazole Sodium. Curr Drug Deliv. 2009 Oct 1;6(5):505–10.

Haque MdA, Kurokawa T, Gong JP. Super tough double network hydrogels and their application as biomaterials. Polymer. 2012 Apr 17;53(9):1805–22.

Li X, Wang H, Li D, Long S, Zhang G, Wu Z. Dual Ionically Cross-linked Double-Network Hydrogels with High Strength, Toughness, Swelling Resistance, and Improved 3D Printing Processability. ACS Appl Mater Interfaces. 2018 Sep 19;10(37):31198–207.

Mishra RK, Datt M, Banthia AK. Synthesis and Characterization of Pectin/PVP Hydrogel Membranes for Drug Delivery System. AAPS PharmSciTech. 2008 Jun 1;9(2):395–403.

Sharma S, Jain P, Tiwari S. Dynamic imine bond based chitosan smart hydrogel with magnified mechanical strength for controlled drug delivery. Int J Biol Macromol. 2020 Oct 1;160:489–95.

Pourjavadi A, Kurdtabar M, Mahdavinia GR, Hosseinzadeh H. Synthesis and super-swelling behavior of a novel protein-based superabsorbent hydrogel. Polym Bull. 2006 Oct 1;57(6):813–24.

Zahra Q, Minhas MU, Khan S, Wu PC, Suhail M, Iqbal R, Bashir M. Fabrication of polyethylene glycol hydrogels with enhanced swelling; loading capacity and release kinetics. Polym Bull. 2022 Jul 1;79(7):5389–415.

Lazaridou M, Nanaki S, Zamboulis A, Papoulia C, Chrissafis K, Klonos PA, Kyritsis A, Vergkizi-Nikolakaki S, Kostoglou M, Bikiaris DN. Super absorbent chitosan-based hydrogel sponges as carriers for caspofungin antifungal drug. Int J Pharm. 2021 Sep 5;606:120925.

Cai B, Luo Y, Guo Q, Zhang X, Wu Z. A glucose-sensitive block glycopolymer hydrogel based on dynamic boronic ester bonds for insulin delivery. Carbohydr Res. 2017 Jun 5;445:32–9.

Zhang J, Zhao D, Lu K. Mechanisms and influencing factors of peptide hydrogel formation and biomedicine applications of hydrogels. Soft Matter. 2023 Oct 11;19(39):7479–93.

Parhi R. Cross-Linked Hydrogel for Pharmaceutical Applications: A Review. Adv Pharm Bull. 2017 Dec;7(4):515–30.

Pragya A, Mutalik S, Younas MW, Pang SK, So PK, Wang F, Zheng Z, Noor N. Dynamic cross-linking of an alginate-acrylamide tough hydrogel system: time-resolved in situ mapping of gel self-assembly. RSC Adv. 2021 Mar 10;11(18):10710–26.

Bashir S, Hina M, Iqbal J, Rajpar AH, Mujtaba MA, Alghamdi NA, Wageh S, Ramesh K, Ramesh S. Fundamental Concepts of Hydrogels: Synthesis, Properties, and Their Applications. Polymers. 2020 Nov 16;12(11).

Berger J, Reist M, Mayer JM, Felt O, Gurny R. Structure and interactions in chitosan hydrogels formed by complexation or aggregation for biomedical applications. Eur J Pharm Biopharm Off J Arbeitsgemeinschaft Pharm Verfahrenstechnik EV. 2004 Jan;57(1):35–52.

Xue X, Hu Y, Wang S, Chen X, Jiang Y, Su J. Fabrication of physical and chemical crosslinked hydrogels for bone tissue engineering. Bioact Mater. 2022;12:327–39.

Naranjo-Alcazar R, Bendix S, Groth T, Gallego Ferrer G. Research Progress in Enzymatically Cross-Linked Hydrogels as Injectable Systems for Bioprinting and Tissue Engineering. Gels [Internet]. 2023;9(3). Available from: https://www.mdpi.com/2310-2861/9/3/230

Badali E, Hosseini M, Mohajer M, Hassanzadeh S, Saghati S, Hilborn J, Khanmohammadi M. Enzymatic Crosslinked Hydrogels for Biomedical Application. Polym Sci Ser A. 2022 Feb;63.

Ma H, Peng Y, Zhang S, Zhang Y, Min P. Effects and Progress of Photo-Crosslinking Hydrogels in Wound Healing Improvement. Gels [Internet]. 2022;8(10). Available from: https://www.mdpi.com/2310-2861/8/10/609

Czarnecki S, Rossow T, Seiffert S. Hybrid Polymer-Network Hydrogels with Tunable Mechanical Response. Polymers [Internet]. 2016;8(3). Available from: https://www.mdpi.com/2073-4360/8/3/82

Xu J, Zhu X, Zhao J, Ling G, Zhang P. Biomedical applications of supramolecular hydrogels with enhanced mechanical properties. Adv Colloid Interface Sci. 2023 Nov;321:103000.

Palmese LL, Thapa RK, Sullivan MO, Kiick KL. Hybrid hydrogels for biomedical applications. Curr Opin Chem Eng. 2019 Jun;24:143–57.

Villalba-Rodríguez AM, Martínez-González S, Sosa-Hernández JE, Parra-Saldívar R, Bilal M, Iqbal HMN. Nanoclay/Polymer-Based Hydrogels and Enzyme-Loaded Nanostructures for Wound Healing Applications. Gels Basel Switz. 2021 May 14;7(2).

Zhang Y, Huang Y. Rational Design of Smart Hydrogels for Biomedical Applications. Front Chem. 2020;8:615665.

Golmohamadi M, Davis TA, Wilkinson KJ. Diffusion and partitioning of cations in an agarose hydrogel. J Phys Chem A. 2012 Jun 28;116(25):6505–10.

Lacroce E, Rossi F. Polymer-based thermoresponsive hydrogels for controlled drug delivery. Expert Opin Drug Deliv. 2022 Oct;19(10):1203–15.

MORIYA G, MAZUMDER R, PADHI S, MISHRA R. GASTRORENTENTIVE HYDROGELS RESPONSIVE TO EXTERNAL STIMULI FOR NOVEL DRUG DELIVERY. Int J App Pharm. 2024 Jul. 7;16(4):1-14.

Kakkar V, Narula P. Role of molecularly imprinted hydrogels in drug delivery - A current perspective. Int J Pharm. 2022 Sep 25;625:121883.

GHANEM AM. A REVIEW ON RECENT ADVANCES IN TRANSDERMAL DRUG DELIVERY SYSTEMS OF TAMSULOSIN. Int J Appl Pharm. 2024 Mar;16(2):28–33.

Khan F, Atif M, Haseen M, Kamal S, Khan MS, Shahid S, Nami SAA. Synthesis, classification and properties of hydrogels: their applications in drug delivery and agriculture. J Mater Chem B. 2022 Jan 5;10(2):170–203.

Dimatteo R, Darling NJ, Segura T. In situ forming injectable hydrogels for drug delivery and wound repair. Adv Drug Deliv Rev. 2018 Mar 1;127:167–84.

Mo F, Jiang K, Zhao D, Wang Y, Song J, Tan W. DNA hydrogel-based gene editing and drug delivery systems. Adv Drug Deliv Rev. 2021 Jan;168:79–98.

Andriano K. Controlled release of highly water soluble drugs from the SQZgel oral drug delivery system. Drug Deliv Technol. 2010 Jan;10:42.

https://www.rxlist.com/metrogel-vaginal-drug.htm#description . [Last assessed on 20 Feb 2024]

https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/125277s000PharmR_P1.pdf [Last accessed on 20 Aug 2024]

https://www.drugs.com/pro/maxidex.html. [Last accessed on 20 Feb 2024]

https://www.medicines.org.uk/emc/product/135/smpc#gref. [Last accessed on 15 Mar 2024]

https://www.supprelinla.com/. [Last accessed on 15 Mar2024]