Studies on the Loading and Release of Metformin HCl Using Hydrogels with EGDMA and MBA as Crosslinkers

https://doi.org/10.22146/ijc.95826

Ariyaldi Ariyaldi(1), Noverra Mardhatillah Nizardo(2*), Maria Lucia Ardhani Dwi Lestari(3)

(1) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, Depok 16424, Indonesia
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, Depok 16424, Indonesia
(3) Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Campus C Mulyorejo, Surabaya 60115, Indonesia; Pharmaceutical Material Engineering and Processing Research Group, Faculty of Pharmacy, Universitas Airlangga, Campus C Mulyorejo, Surabaya 60115, Indonesia
(*) Corresponding Author

Abstract


Hydrogel poly(N-vinylcaprolactam-co-2-(dimethylamino)ethylmethacrylate) or (P(NVCL-co-DMAEMA)) containing the active drug metformin HCl were synthesized using the free radical polymerization method in the presence of DMAEMA and NVCL monomers by using two different crosslinkers: ethylene glycol dimethacrylate (EGDMA) and methylene bisacrylamide (MBA). FTIR spectra confirmed the successful formation of hydrogel and its loading with metformin HCl. SEM analysis revealed the physical shape and surface features. Regarding physical appearance, the texture of the hydrogel is sticky and elastic. When the hydrogel was immersed in a solution, it swelled, and returned to its original shape after drying. Additionally, the chemical degradation temperature is thermally stable at 329.75 °C. The loading test results showed that the active drug in EGDMA was 18.38 (% w/w) and 26.19 (% w/w) in MBA as crosslinkers, loaded within 24 h. The drug-loaded hydrogel containing EGDMA as crosslinkers in pH 7.4 had the highest drug release in 24 h compared to MBA. Then, the drug released from hydrogel with EGDMA in pH 2 had the highest drug release than MBA within 30 min. The P(NVCL-co-DMAEMA) hydrogel has the potential for a drug delivery system. However, additional optimizations are necessary to improve the efficiency of the hydrogels as a carrier.

Keywords


hydrogel; ethylene glycol dimethacrylate; methylene bisacrylamide; metformin HCl; controlled release

Full Text:

Full Text PDF


References

[1] Romero, J.F., Díaz-Barrios, A., and González, G., 2021, Biocompatible thermo-responsive N-vinylcaprolactam based hydrogels for controlled drug delivery systems, Bionatura, 6 (2), 1712–1719.

[2] Sudjaroen, Y., Thongkao, K., and Thongmuang, P., 2023, A physiochemical study on drug delivery of metformin HCl-loaded CS-PLGA nanoparticles, Int. J. Appl. Pharm., 15 (1), 66–71.

[3] Hoffman, A.S., 1995, "Intelligent" Polymers in medicine and biotechnology, Artif. Organs, 19 (5), 458–467.

[4] Saikia, A.K., Aggarwal, S., and Mandal, U.K., 2013, Preparation and controlled drug release characteristics of thermoresponsive PEG/poly(NIPAM-co-AMPS) hydrogels, Int. J. Polym. Mater. Polym. Biomater., 62 (1), 39–44.

[5] Fallon, M., Halligan, S., Pezzoli, R., Geever, L., and Higginbotham, C., 2019, Synthesis and characterisation of novel temperature and pH sensitive physically cross-linked poly(N-vinylcaprolactam-co-itaconic acid) hydrogels for drug delivery, Gels, 5 (3), 41.

[6] Taktak, F., 2016, Rapid deswelling of PDMAEMA hydrogel in response to pH and temperature changes and its application in controlled drug delivery, AKU J. Sci. Eng., 16(1), 68–75.

[7] Bustamante-Torres, M., Romero-Fierro, D., Arcentales-Vera, B., Palomino, K., Magaña, H., and Bucio, E., 2021, Hydrogels classification according to the physical or chemical interactions and as stimuli-sensitive materials, Gels, 7 (4), 182.

[8] Nizardo, N.M., Fadhilah, R.H., and Anggraningrum, I.T., 2023, Thermo- and pH-responsive behavior of poly(N-isopropylacrylamide)-block-poly[(2-dimethylamino)ethyl methacrylate], Indones. J. Chem., 23 (2), 449–460.

[9] Sandjaja, M., and Lestari, M.L.A.D., 2017, Investigation of effect of adding hydrophobically modified water soluble polymers on the structure and viscosity of anionic vesicle dispersion, Indones. J. Chem., 17 (1), 86–94.

[10] Podaru, I.A., Stănescu, P.O., Ginghină, R., Stoleriu, Ş., Trică, B., Şomoghi, R., and Teodorescu, M., 2022, Poly(N-vinylpyrrolidone)–Laponite XLG nanocomposite hydrogels: Characterization, properties and comparison with divinyl monomer-crosslinked hydrogels, Polymers, 14 (19), 4216.

[11] Bashir, S., Zafar, N., Lebaz, N., Mahmood, A., and Elaissari, A., 2020, Hydroxypropyl methylcellulose-based hydrogel copolymeric for controlled delivery of galantamine hydrobromide in dementia, Processes, 8 (11), 1350.

[12] Minhas, M.U., Ahmad, M., Ali, L., and Sohail, M., 2013, Synthesis of chemically cross-linked polyvinyl alcohol-co-poly (methacrylic acid) hydrogels by copolymerization; A potential graft-polymeric carrier for oral delivery of 5-fluorouracil, Daru, J. Pharm. Sci., 21 (1), 44.

[13] Bukhari, S.M.H., Khan, S., Rehanullah, M., and Ranjha, N.M., 2015, Synthesis and characterization of chemically cross-linked acrylic acid/gelatin hydrogels: Effect of pH and composition on swelling and drug release, Int. J. Polym. Sci., 2015 (1), 187961.

[14] Caroline, D.S.M., and Rekha, M.R., 2022, Exploring the efficacy of ethylene glycol dimethacrylate crosslinked cationised pullulan for gene delivery in cancer cells, J. Drug Delivery Sci. Technol., 68, 103067.

[15] Farshforoush, P., Ghanbarzadeh, S., Goganian, A.M., and Hamishehka, H., 2017, Novel metronidazole-loaded hydrogel as a gastroretentive drug delivery system, Iran. Polym. J., 26 (12), 895–901.

[16] Dave, P.N., Macwan, P.M., and Kamaliya, B., 2023, Synthesis and characterization of biodegradable gum ghatti-cl-poly(AA-co-NIPAm)/GO based hydrogel for metformin and sodium diclofenac combined drug delivery system, Colloids Surf., A, 673, 131815.

[17] Noreen, S., Hasan, S., Ghumman, S.A., Anwar, S., Gondal, H.Y., Batool, F., and Noureen, S., 2023, Formulation, statistical optimization, and in vivo pharmacodynamics of Cydonia oblonga mucilage/alginate mucoadhesive microspheres for the delivery of metformin HCl, ACS Omega, 8 (6), 5925–5938.

[18] Desai, D., Wong, B., Huang, Y., Ye, Q., Tang, D., Guo, H., Huang, M., and Timmins, P., 2014, Surfactant-mediated dissolution of metformin hydrochloride tablets: Wetting effects versus ion pairs diffusivity, J. Pharm. Sci., 103 (3), 920–926.

[19] Mishra, R.K., and Ray, A.R., 2011, Synthesis and characterization of poly{N-[3-(dimethylamino) propyl] methacrylamide-co-itaconic acid} hydrogels for drug delivery, J. Appl. Polym. Sci., 119 (6), 3199–3206.

[20] Çakal, E., and Çavuş, S., 2010, Novel poly(N-vinylcaprolactam-co-2-(diethylamino)ethyl methacrylate) gels: Characterization and detailed investigation on their stimuli-sensitive behaviors and network structure, Ind. Eng. Chem. Res., 49 (22), 11741–11751.

[21] Durkut, S., 2019, Thermoresponsive poly(N-vinylcaprolactam)-g-galactosylated chitosan hydrogel: Synthesis, characterization, and controlled release properties, Int. J. Polym. Mater. Polym. Biomater., 68 (17), 1034–1047.

[22] Demirel, G.B., and von Klitzing, R., 2013, A new multiresponsive drug delivery system using smart nanogels, ChemPhysChem, 14 (12), 2833–2840.

[23] Ashames, A., Ullah, K., Al-Tabakha, M., Khan, S.A., Hassan, N., Mannan, A., Ikram, M., Buabeid, M., and Murtaza, G., 2022, Development, characterization and in-vitro evaluation of guar gum based new polymeric matrices for controlled delivery using metformin HCl as model drug, PLoS One, 17 (7), e0271623.

[24] Iwohn, M., Seifermann, M., Reiser, P., Höpfner, J., El Khaled El Faraj, R., Heißler, S., Popova, A., and Levkin, P.A., 2023, OligoHydrogelArray (OHA) for parallelized solid-phase extraction of oligonucleotides, Adv. Mater. Interfaces, 10 (21), 2300227.

[25] Giubertoni, G., Sofronov, O.O., and Bakker, H.J., 2020, Effect of intramolecular hydrogen-bond formation on the molecular conformation of amino acids, Commun. Chem., 3 (1), 84.

[26] Zhang, H., Quan, L., Gao, A., Tong, Y., Shi, F., and Xu, L., 2020, Thermal analysis and crystal structure of poly(acrylonitrile-co-itaconic acid) copolymers synthesized in water, Polymers, 12 (1), 221.

[27] Park, H., Guo, X., Temenoff, J.S., Tabata, Y., Caplan, A.I., Kasper, F.K., and Mikos, A.G., 2009, Effect of swelling ratio of injectable hydrogel composites on chondrogenic differentiation of encapsulated rabbit marrow mesenchymal stem cells in vitro, Biomacromolecules, 10 (3), 541–546.

[28] Joo, S.B., Gulfram, M., Jo, S.H., Jo, Y.J., Vu, T.T., Park, S.H., Gal, Y.S., and Lim, K.T., 2022, Fast absorbent and highly bioorthogonal hydrogels developed by IEDDA click reaction for drug delivery application, Materials, 15 (20), 7128.

[29] Hoti, G., Caldera, F., Cecone, C., Rubin Pedrazzo, A., Anceschi, A., Appleton, S.L., Khazaei Monfared, Y., and Trotta, F., 2021, Effect of the cross-linking density on the swelling and rheological behavior of ester-bridged β-cyclodextrin nanosponges, Materials, 14 (3), 478.

[30] Nasution, H., Harahap, H., Dalimunthe, N.F., Ginting, M.H.S., Jaafar, M., Tan, O.O.H., Aruan, H.K., and Herfananda, A.L., 2022, Hydrogel and effects of crosslinking agent on cellulose-based hydrogels: A review, Gels, 8 (9), 568.

[31] Kasiński, A., Zielińska-Pisklak, M., Oledzka, E., and Obczak, M., 2020, Smart hydrogels – Synthetic stimuli-responsive antitumor drug release systems, Int. J. Nanomed., 15, 4541–4572.

[32] Reyes-Ortega, F., 2014, “pH-Responsive polymers: Properties, synthesis and applications” in Smart Polymers and their Applications, Woodhead Publishing, Cambridge, UK, 45–92.

[33] Putra, I.M.W.A., and Kusumawati, I.G.A.W., 2018, The use of clinoptilolites as carrier of metformin hydrochloride in drug delivery system: In vitro drug release study, Asian J. Pharm. Clin. Res., 11 (11), 285–289.

[34] Mathews, A.S., Ha, C.S., Cho, W.J., and Kim, I., 2006, Drug delivery system based on covalently bonded poly[N-isopropylacrylamide-co-2-hydroxyethylacrylate]-based nanoparticle networks, Drug Delivery, 13 (4), 245–251.

[35] Abedi, F., Davaran, S., Hekmati, M., Akbarzadeh, A., Baradaran, B., and Moghaddam, S.V., 2021, An improved method in fabrication of smart dual-responsive nanogels for controlled release of doxorubicin and curcumin in HT-29 colon cancer cells, J. Nanobiotechnol., 19 (1), 18.

[36] Barleany, D.R., Ananta, C.V., Maulina, F., Rochmat, A., Alwan, H., and Erizal, E., 2020, Controlled release of metformin hydrogen chloride from stimuli-responsive hydrogel based on poly(N-isopropylacrylamide)/chitosan/polyvinyl alcohol composite, Int. J. Technol., 11 (3), 511–521.

[37] Cortez-Lemus, N.A., and Licea-Claverie, A., 2016, Poly(N-vinylcaprolactam), a comprehensive review on a thermoresponsive polymer becoming popular, Prog. Polym. Sci., 53, 1–51.

[38] Aderibigbe, B.A., and Mhlwatika, Z., 2016, Dual release kinetics of antimalarials from soy protein isolate-carbopol-polyacrylamide based hydrogels, J. Appl. Polym. Sci., 133 (37), 43918.

[39] Hu, Y., Mei, Z., and Hu, X., 2015, pH-Sensitive interpenetrating network hydrogels based on pachyman and its carboxymethylated derivatives for oral drug delivery, J. Polym. Res., 22 (6), 98.

[40] Alexander, A., Ajazuddin, A., Khan, J., Saraf, S., and Saraf, S., 2014, Polyethylene glycol (PEG)-Poly(N-isopropylacrylamide) (PNIPAAm) based thermosensitive injectable hydrogels for biomedical applications, Eur. J. Pharm. Biopharm., 88 (3), 575–585.



DOI: https://doi.org/10.22146/ijc.95826

Article Metrics

Abstract views : 34 | views : 0


Copyright (c) 2024 Indonesian Journal of Chemistry

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

 


Indonesian Journal of Chemistry (ISSN 1411-9420 /e-ISSN 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.

Web
Analytics View The Statistics of Indones. J. Chem.