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Nanoscience & Nanotechnology-Asia

Editor-in-Chief

ISSN (Print): 2210-6812
ISSN (Online): 2210-6820

Review Article

Hydrogels as Potential Controlled Drug Delivery System: Drug Release Mechanism and Applications

Author(s): Smriti Ojha, Saurabh Sharma and Sudhanshu Mishra*

Volume 13, Issue 3, 2023

Published on: 25 May, 2023

Article ID: e170423215845 Pages: 9

DOI: 10.2174/2210681213666230417083119

Price: $65

Abstract

Hydrogels are one of the most extensively studied novel drug delivery dosage forms owing to their satisfactory results in drug delivery in various conditions, including pain management, immunomodulation, carcinomas, healing of wounds, and cardiology. A crosslinked polymeric network and an optimum amount of water combine to form hydrogels. Due to their specific properties such as biocompatibility, biodegradability, hydrophilicity, and non-toxic to biological tissues, hydrogels are demanding biomaterials. Furthermore, due to their programmable physical characteristics, controlled degradation behavior, and capability to preserve unstable medicines from degradation, hydrogels serve as an advanced drug delivery system in which diverse physiochemical interactions with the polymeric matrix containing embedded medications control their release. Despite significant challenges remaining, there has been significant progress in recent years in overcoming the clinical and pharmacological constraints of hydrogels for drug delivery applications This review covers various hydrogel-forming polymers, strategies for crosslinking of gelling agents, and release mechanisms from the hydrogel. Moreover, the current work includes a few marketed hydrogel preparations and patent rights associated with it, describing its mechanism of action against the underlying diseases.

Graphical Abstract

[1]
Bernhard, S.; Tibbitt, M.W. Supramolecular engineering of hydrogels for drug delivery. Adv. Drug Deliv. Rev., 2021, 171, 240-256.
[http://dx.doi.org/10.1016/j.addr.2021.02.002] [PMID: 33561451]
[2]
Ghasemiyeh, P.; Mohammadi-Samani, S. Hydrogels as drug delivery systems; pros and cons. Trends Pharma. Sci., 2019, 5(1), 7-24.
[3]
Vigata, M.; Meinert, C.; Hutmacher, D.W.; Bock, N. Hydrogels as drug delivery systems: A review of current characterization and evaluation techniques. Pharmaceutics, 2020, 12(12), 1188.
[http://dx.doi.org/10.3390/pharmaceutics12121188] [PMID: 33297493]
[4]
In situ gel: New trends in controlled and sustained drug delivery system. Int. J. Pharm. Tech. Res., 2010, 2(2), 1398-1408.
[5]
Xinming, L.; Yingde, C.; Lloyd, A.W.; Mikhalovsky, S.V.; Sandeman, S.R.; Howel, C.A.; Liewen, L. Polymeric hydrogels for novel contact lens-based ophthalmic drug delivery systems: A review. Cont. Lens Anterior Eye, 2008, 31(2), 57-64.
[http://dx.doi.org/10.1016/j.clae.2007.09.002] [PMID: 17962066]
[6]
Tian, Y.; Grishkewich, N.; Bromberg, L.; Hatton, T.A.; Tam, K.C. Cross-linked Pluronic- g -Polyacrylic acid microgel system for the controlled release of doxorubicin in pharmaceutical formulations. Eur. J. Pharm. Biopharm., 2017, 114, 230-238.
[http://dx.doi.org/10.1016/j.ejpb.2017.01.009] [PMID: 28126393]
[7]
Hajikarimi, A.; Sadeghi, M. Free radical synthesis of cross-linking gelatin base poly NVP/acrylic acid hydrogel and nanoclay hydrogel as cephalexin drug deliver. J. Polym. Res., 2020, 27(3), 57.
[http://dx.doi.org/10.1007/s10965-020-2020-1]
[8]
Singh, B.; Ram, K.; Singh, B. Development and characterization of azadirachta indica gum-poly(2-hydroxyethyl methacrylate) crosslinked co-polymeric hydrogels for drug delivery applications. Chem. Phys. Lett., 2022, 792139401
[http://dx.doi.org/10.1016/j.cplett.2022.139401]
[9]
Guo, J.; Sun, H.; Lei, W.; Tang, Y.; Hong, S.; Yang, H.; Tay, F.R.; Huang, C. MMP-8-responsive polyethylene glycol hydrogel for intraoral drug delivery. J. Dent. Res., 2019, 98(5), 564-571.
[http://dx.doi.org/10.1177/0022034519831931] [PMID: 30876379]
[10]
Wang, K.; Xu, X.; Wang, Y.; Yan, X.; Guo, G.; Huang, M.; Luo, F.; Zhao, X.; Wei, Y.; Qian, Z. Synthesis and characterization of poly(methoxyl ethylene glycol-caprolactone-co-methacrylic acid-co-poly(ethylene glycol) methyl ether methacrylate) pH-sensitive hydrogel for delivery of dexamethasone. Int. J. Pharm., 2010, 389(1-2), 130-138.
[http://dx.doi.org/10.1016/j.ijpharm.2010.01.026] [PMID: 20096758]
[11]
Bartil, T.; Bounekhel, M.; Cedric, C.; Jeerome, R. Swelling behavior and release properties of pH-sensitive hydrogels based on methacrylic derivatives. Acta Pharm., 2007, 57(3), 301-314.
[http://dx.doi.org/10.2478/v10007-007-0024-6] [PMID: 17878110]
[12]
Mohd Amin, M.C.I.; Ahmad, N.; Pandey, M.; Jue Xin, C. Stimuli-responsive bacterial cellulose-g-poly(acrylic acid-co-acrylamide) hydrogels for oral controlled release drug delivery. Drug Dev. Ind. Pharm., 2014, 40(10), 1340-1349.
[http://dx.doi.org/10.3109/03639045.2013.819882] [PMID: 23875787]
[13]
Clara, I.; Lavanya, R.; Natchimuthu, N. pH and temperature responsive hydrogels of poly(2-acrylamido-2-methyl-1-propanesulfonic acid-co-methacrylic acid): Synthesis and swelling characteristics. J. Macromol. Sci. Part A Pure Appl. Chem., 2016, 53(8), 492-499.
[http://dx.doi.org/10.1080/10601325.2016.1189282]
[14]
Singh, R.; Mahto, V. Synthesis, characterization and evaluation of polyacrylamide graft starch/clay nanocomposite hydrogel system for enhanced oil recovery. Petrol. Sci., 2017, 14(4), 765-779.
[http://dx.doi.org/10.1007/s12182-017-0185-y]
[15]
Matanović, M.R.; Kristl, J.; Grabnar, P.A. Thermoresponsive polymers: Insights into decisive hydrogel characteristics, mechanisms of gelation, and promising biomedical applications. Int. J. Pharm., 2014, 472(1-2), 262-275.
[http://dx.doi.org/10.1016/j.ijpharm.2014.06.029] [PMID: 24950367]
[16]
Rajabi, M.; McConnell, M.; Cabral, J.; Ali, M.A. Chitosan hydrogels in 3D printing for biomedical applications. Carbohydr. Polym., 2021, 260117768
[http://dx.doi.org/10.1016/j.carbpol.2021.117768] [PMID: 33712126]
[17]
Rico-García, D.; Ruiz-Rubio, L.; Pérez-Alvarez, L.; Hernández-Olmos, S.L.; Guerrero-Ramírez, G.L.; Vilas-Vilela, J.L. Lignin-based hydrogels: Synthesis and applications. Polymers, 2020, 12(1), 81.
[http://dx.doi.org/10.3390/polym12010081] [PMID: 31947714]
[18]
Maitra, J.; Shukla, V.K. Cross-linking in hydrogels- A review. Am. J. Pol. Sci., 2014, 4(2), 25-31.
[19]
Liu, Y.; Sui, Y.; Liu, C.; Liu, C.; Wu, M.; Li, B.; Li, Y. A physically crosslinked polydopamine/nanocellulose hydrogel as potential versatile vehicles for drug delivery and wound healing. Carbohydr. Polym., 2018, 188, 27-36.
[http://dx.doi.org/10.1016/j.carbpol.2018.01.093] [PMID: 29525166]
[20]
Hu, W.; Wang, Z.; Xiao, Y.; Zhang, S.; Wang, J. Advances in crosslinking strategies of biomedical hydrogels. Biomater. Sci., 2019, 7(3), 843-855.
[http://dx.doi.org/10.1039/C8BM01246F] [PMID: 30648168]
[21]
Akhtar, M.F.; Hanif, M.; Ranjha, N.M. Methods of synthesis of hydrogels. A review. Saudi Pharm. J., 2016, 24(5), 554-559.
[http://dx.doi.org/10.1016/j.jsps.2015.03.022] [PMID: 27752227]
[22]
Hennink, W.E.; van Nostrum, C.F. Novel crosslinking methods to design hydrogels. Adv. Drug Deliv. Rev., 2012, 64, 223-236.
[http://dx.doi.org/10.1016/j.addr.2012.09.009] [PMID: 11755704]
[23]
a) Saini, K. Preparation method, properties and crosslinking of hydrogel: A review. PharmaTutor, 2017, 5(1), 27-36.;
b) Alvarez-Lorenzo, C.; Blanco-Fernandez, B.; Puga, A.M.; Concheiro, A. Crosslinked ionic polysaccharides for stimuli-sensitive drug delivery. Adv. Drug Deliv. Rev., 2013, 65(9), 1148-1171.
[PMID: 23639519]
[24]
Chen, L.; Yan, D.; Wu, N.; Yao, Q.; Sun, H.; Pang, Y.; Fu, Y. Injectable bio-responsive hydrogel for therapy of inflammation related eyelid diseases. Bioact. Mater., 2021, 6(10), 3062-3073.
[http://dx.doi.org/10.1016/j.bioactmat.2021.02.040] [PMID: 33778188]
[25]
Singh, N.K.; Lee, D.S. In situ gelling pH- and temperature-sensitive biodegradable block copolymer hydrogels for drug delivery. J. Control. Release, 2014, 193, 214-227.
[http://dx.doi.org/10.1016/j.jconrel.2014.04.056] [PMID: 24815421]
[26]
Choi, B.; Loh, X.J.; Tan, A.; Loh, C.K.; Ye, E.; Joo, M.K.; Jeong, B. Introduction to in situ forming hydrogels for biomedical applications. In: In Situ Gelling Polymers; Springer: Singapore, 2015; pp. 5-35.
[27]
Zheng, S.Y.; Liu, C.; Jiang, L.; Lin, J.; Qian, J.; Mayumi, K.; Wu, Z.L.; Ito, K.; Zheng, Q. Slide-ring cross-links mediated tough metallosupramolecular hydrogels with superior self-recoverability. Macromolecules, 2019, 52(17), 6748-6755.
[http://dx.doi.org/10.1021/acs.macromol.9b01281]
[28]
Estabrook, D.A.; Chapman, J.O.; Yen, S.T.; Lin, H.H.; Ng, E.T.; Zhu, L.; van de Wouw, H.L.; Campàs, O.; Sletten, E.M. Macromolecular crowding as an intracellular stimulus for responsive nanomaterials. J. Am. Chem. Soc., 2022, 144(37), 16792-16798.
[http://dx.doi.org/10.1021/jacs.2c03064] [PMID: 36084194]
[29]
Chandran, R.; Mohd Tohit, E.R.; Stanslas, J.; Tuan Mahmood, T.M.; Salim, N. Factors influencing the swelling behaviour of polymethyl vinyl ether-co-maleic acid hydrogels crosslinked by polyethylene glycol. J. Drug Deliv. Sci. Technol., 2022, 68103080
[http://dx.doi.org/10.1016/j.jddst.2021.103080]
[30]
Ikejiri, S.; Takashima, Y.; Osaki, M.; Yamaguchi, H.; Harada, A. Solvent-free photoresponsive artificial muscles rapidly driven by molecular machines. J. Am. Chem. Soc., 2018, 140(49), 17308-17315.
[http://dx.doi.org/10.1021/jacs.8b11351] [PMID: 30415536]
[31]
Siepmann, J.; Siepmann, F. Modeling of diffusion controlled drug delivery. J. Control. Release, 2012, 161(2), 351-362.
[http://dx.doi.org/10.1016/j.jconrel.2011.10.006] [PMID: 22019555]
[32]
Li, T.; Jang, Y.; Choi, J.G.; Lee, D.Y.; Hyeon, J.S.; Kim, S.J. Bioinspired self-coiled hydrogel fiber with high water content and stretchability. ACS Appl. Polym. Mater., 2022, 4(12), 9125-9131.
[http://dx.doi.org/10.1021/acsapm.2c01458]
[33]
Ende, M.T.; Mikos, A.G. Diffusion-controlled delivery of proteins from hydrogels and other hydrophilic systems. In: Protein Delivery; , 2002; pp. 139-165.
[http://dx.doi.org/10.1007/0-306-46803-4_5]
[34]
Ferrero, C.; Massuelle, D.; Doelker, E. Towards elucidation of the drug release mechanism from compressed hydrophilic matrices made of cellulose ethers. II. Evaluation of a possible swelling-controlled drug release mechanism using dimensionless analysis. J. Control. Release, 2010, 141(2), 223-233.
[http://dx.doi.org/10.1016/j.jconrel.2009.09.011] [PMID: 19766681]
[35]
Rasool, A.; Rizwan, M.; Islam, A.; Abdullah, H.; Shafqat, S.S.; Azeem, M.K.; Rasheed, T.; Bilal, M. Chitosan‐based smart polymeric hydrogels and their prospective applications in biomedicine. Stärke, 2021.2100150
[http://dx.doi.org/10.1002/star.202100150]
[36]
Pal, K.; Singh, V.K.; Anis, A.; Thakur, G.; Bhattacharya, M.K. Hydrogel-based controlled release formulations: Designing considerations, characterization techniques and applications. Polym. Plast. Technol. Eng., 2013, 52(14), 1391-1422.
[http://dx.doi.org/10.1080/03602559.2013.823996]
[37]
Mah, F.S. Effect on gel formation time of adding topical ophthalmic medications to resure sealant, an in situ hydrogel. J. Ocul. Pharmacol. Ther., 2016, 32(6), 396-399.
[http://dx.doi.org/10.1089/jop.2015.0112] [PMID: 27249170]
[38]
Aswathy, S.H.; Narendrakumar, U.; Manjubala, I. Commercial hydrogels for biomedical applications. Heliyon, 2020, 6(4)e03719
[http://dx.doi.org/10.1016/j.heliyon.2020.e03719] [PMID: 32280802]
[39]
Rani, A.; De Leon-Rodriguez, L.M.; Kavianinia, I.; McGillivray, D.J.; Williams, D.E.; Brimble, M.A. Synthesis and characterization of mono S -lipidated peptide hydrogels: A platform for the preparation of reactive oxygen species responsive materials. Org. Biomol. Chem., 2021, 19(16), 3665-3677.
[http://dx.doi.org/10.1039/D1OB00355K] [PMID: 33908574]
[40]
Kurakula, M.; Rao, G.K.; Kiran, V.; Hasnain, M.S.; Nayak, A.K. Chapter 13 - Alginate-based hydrogel systems for drug releasing in wound healing. In: Alginates in Drug Delivery; , 2020; pp. 323-358.
[http://dx.doi.org/10.1016/B978-0-12-817640-5.00013-3]
[41]
Kaur, G.; Narayanan, G.; Garg, D.; Sachdev, A.; Matai, I. Biomaterials-based regenerative strategies for skin tissue wound healing. ACS Appl. Bio Mater., 2022, 5(5), 2069-2106.
[http://dx.doi.org/10.1021/acsabm.2c00035] [PMID: 35451829]
[42]
Hayati, F.; Ghamsari, S.M.; Dehghan, M.M.; Oryan, A. Effects of carbomer 940 hydrogel on burn wounds: An in vitro and in vivo study. J. Dermatolog. Treat., 2018, 29(6), 593-599.
[http://dx.doi.org/10.1080/09546634.2018.1426823] [PMID: 29316829]
[43]
McNickle, A.G.; Provencher, M.T.; Cole, B.J. Overview of existing cartilage repair technology. Sports Med. Arthrosc. Rev., 2008, 16(4), 196-201.
[http://dx.doi.org/10.1097/JSA.0b013e31818cdb82] [PMID: 19011550]
[44]
Cavalcanti, B.N.; Zeitlin, B.D.; Nör, J.E. A hydrogel scaffold that maintains viability and supports differentiation of dental pulp stem cells. Dent. Mater., 2013, 29(1), 97-102.
[http://dx.doi.org/10.1016/j.dental.2012.08.002] [PMID: 22901827]
[45]
Caló, E.; Khutoryanskiy, V.V. Biomedical applications of hydrogels: A review of patents and commercial products. Eur. Polym. J., 2015, 65, 252-267.
[http://dx.doi.org/10.1016/j.eurpolymj.2014.11.024]
[46]
Taaca, K.L.M.; Prieto, E.I.; Vasquez, M.R., Jr Current trends in biomedical hydrogels: From traditional crosslinking to plasma-assisted synthesis. Polymers, 2022, 14(13), 2560.
[http://dx.doi.org/10.3390/polym14132560] [PMID: 35808607]
[47]
Sthengel, E.; Israelsson, A.; Wennerholm, J. A biphasic hydrogel formulation and methods of production and use thereof. Patent US 17/267,806,, 2021.

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