Preparation of new macroporous hydrogel by formation of high internal phase emulsions (HIPEs) template and investigation of controlled release of doxorubicin drug

Document Type : Original Article


Department of Chemistry,, Payame Noor University, Tehran, Iran


During recent years, the development of drug delivery systems based on polymers has created powerful carriers for smart application in nanomedicine for the treatment of diseases. Based on this, the design of polymers that contain various active functional groups to create a suitable interaction with the drug for its loading and release has been considered. Generally, more porosity for more drug loading, biocompatibility of the desired polymer and more water absorption lead to better performance in drug permeation and release.
In this research, the preparation of a template with a high internal phase emulsion (PolyHIPEs) based on polyacrylamide grafting onto sodium alginate (SA) biopolymer via free radical polymerization and PolyHIPEs method of oil-in-water emulsion type is presented. In this work, porous hydrogel with high water swelling (absorption) was prepared by using different concentrations of acrylamide (AAm), surface active agent, cross-linking agent and initiator. The highest equilibrium water swelling value of synthetic porous hydrogel with HIPEs method was 280 g/g, while the water swelling value of prepared hydrogel without HIPEs method was 25 g/g. The open-cell porous hydrogel with water swelling of 280, has average pores of 5-10 μm, 200 nm windows and porosity of 80-85%. Modern instrumental methods such as SEM, AFM, FT-IR, BET and TGA were used to identify the porous hydrogel of PolyHIPEs. The loading and controlled release of the doxorubicin anticancer drug was performed on the optimum porous hydrogel in laboratory conditions. The results showed that smart SA-g-PAAm hydrogel is suitable for drug release at 41 °C and pH 5.5 (cancer cell conditions).


This is an open access article under the CC-BY-SA 4.0 license.(

[1] Aldemir Dikici, B., Claeyssens, F. (2020). Basic principles of emulsion templating and its use as an emerging manufacturing method of tissue engineering scaffolds. Frontiers in Bioengineering and Biotechnology, (8),  875.
[2] Brusotti, G., Calleri, E., Milanese, C., Catenacci, L., Marrubini, G., Sorrenti, M., Girella, A., Massolini, G., Tripodo G. (2016). Rational design of functionalized polyacrylate-based high internal phase emulsion materials for analytical and biomedical uses. Polymer Chemistry, (7),  7436-7445.
[3] Aldemir Dikici, B. (2020). Development of emulsion templated matrices and their use in tissue engineering applications, University of Sheffield, 2020.
[4] Zhang, T., Silverstein, M.S. (2019). Robust, highly porous hydrogels templated within emulsions stabilized using a reactive, crosslinking triblock copolymer. Polymer, (168) 146-154.
[5] Silverstein, M.S. (2014). Emulsion-templated porous polymers: A retrospective perspective Polymer, (55) 304-320.
[6] Silverstein, M.S. (2014). PolyHIPEs: Recent advances in emulsion-templated porous polymers. Progress in Polymer Science, (39) 199-234.
[7] Zhang, H., Cooper, A. (2002). Synthesis of monodisperse emulsion-templated polymer beads by oil-in-water-in-oil (O/W/O) sedimentation polymerization. Chemistry of materials, (14) 4017-4020.
[8] Barbetta, A., Barigelli, E., Dentini,M. (2009). Porous alginate hydrogels: synthetic methods for tailoring the porous texture. Biomacromolecules, (10) 2328-2337.
[9] Rao, K.M., Anbananthan, N., Rajulu, A.V. ( 2011). Bicontinuous highly cross-linked poly (acrylamide-co-ethyleneglycol dimethacrylate) porous materials synthesized within high internal phase emulsions. Soft Matter, (7) 10780-10786.
[10] Fan, X., Zhang, S., Zhu, Y., Chen, J. (2018). Macroporous polymers prepared via frozen UV polymerization of the emulsion-templates stabilized by a low amount of surfactant. RSC advances,  (8) 10141-10147.
[11] Gong, X., Rohm, K., Su, Z., Zhao, B., Renner, J., Manas-Zloczower, I., Feke, D.L. (2020).  Porous hydrogels templated from soy-protein-stabilized high internal phase emulsions. Journal of Materials Science, (55) 17284-17301.
[12] Zhu, Y., Zheng, Y., Wang, F., Wang, A. (2016). Monolithic supermacroporous hydrogel prepared from high internal phase emulsions (HIPEs) for fast removal of Cu2+ and Pb2+. Chemical Engineering Journal, (284) 422-430.
[13] Althubeiti, K.M., Horozov, T.S. (2019). Efficient preparation of macroporous poly (methyl methacrylate) materials from high internal phase emulsion templates. Reactive and Functional Polymers, (142) 207-212.
[14] Naranda, J. , Sušec, M., Maver, , Gradišnik, L., Gorenjak, M., Vukasović, A., Ivković, A., Rupnik, M.S., Vogrin, M. Krajnc, P. (2016). Polyester type polyHIPE scaffolds with an interconnected porous structure for cartilage regeneration. Scientific reports, (6) 1-11.
[15] Krajnc, P., Leber, N., Štefanec, D., Kontrec, S., Podgornik, A. (2005). Preparation and characterisation of poly (high internal phase emulsion) methacrylate monoliths and their application as separation media. Journal of Chromatography A, (1065) 69-73.
[16] Kulkarni, R.V., Inamdar, S.Z., Das, K.K., Biradar, M.S. (2019). Polysaccharide-based stimuli-sensitive graft copolymers for drug delivery,  Polysaccharide Carriers for Drug Delivery. Elsevier. 155-177.
[17] Li, J., Mooney, D.J. (2016). Designing hydrogels for controlled drug delivery. Nature Reviews Materials, (1) 1-17.
[18] Barbetta, A., Dentini, M., Zannoni, E.M., De Stefano, M.E. (2005). Tailoring the porosity and morphology of gelatin-methacrylate polyHIPE scaffolds for tissue engineering applications. Langmuir, (21) 12333-12341.
[19] Myers, D. (2005). The organic chemistry of surfactants, Surfactant Science and Technology, John Wiley & Sons, Inc, 29-79.
[20] Behrouzi, M., Moghadam, P.N. (2018). Synthesis of a new superabsorbent copolymer based on acrylic acid grafted onto carboxymethyl tragacanth. Carbohydrate polymers, (202) 227-235.
[21] Stancu, I.-C., Lungu, A., Dragusin, D.M., Vasile, E., Damian, C., Iovu, H. (2013). Porous gelatin-alginate-polyacrylamide scaffolds with interpenetrating network structure: synthesis and characterization. Soft Materials, (11) 384-393.
[22] İsmail, O., Gökçe Kocabay, Ö. (2021). Absorption and adsorption studies of polyacrylamide/sodium alginate hydrogels. Colloid and Polymer Science, (299) 783-796.
[23] Tanwar, A., Date, P., Ottoor, D. (2021). ZnO NPs incorporated gelatin grafted polyacrylamide hydrogel nanocomposite for controlled release of ciprofloxacin. Colloid and Interface Science Communications, (42) 100413.
[24] Obireddy, S.R., Chintha, M., Kashayi, C.R., Venkata, K.R.K.S., Subbarao, S.M.C. (2020). Gelatin‐coated dual cross‐linked sodium alginate/magnetite nanoparticle microbeads for controlled release of doxorubicin. ChemistrySelect, (5) 10276-10284.
[25] Manjula, B., Varaprasad, K., Sadiku, R., Raju, K.M. (2013). Preparation and characterization of sodium alginate–based hydrogels and their in vitro release studies. Advances in polymer technology, (32).
[26] Xue, Y., Xia, X., Yu, B., Luo, X., Cai, N., Long, S., Yu, F. (2015). A green and facile method for the preparation of a pH-responsive alginate nanogel for subcellular delivery of doxorubicin. RSC advances, (5) 73416-73423.