Scopus     h-index: 24

Document Type : Short Review Article

Authors

1 Department of Chemistry, Payame Noor University, P.O. Box 19395-3697, Tehran, Iran

2 Faculty of Chemistry, Shahrood University of Technology, P.O. Box 316, Shahrood, Iran

10.33945/SAMI/JCR.2020.2.1

Abstract

Anticancer drugs play important roles in cancer treatment. However, these drugs have many disadvantages such as poor solubility, high toxicity, and serious side effects like hair loss, nausea and vomiting, anemia etc. To overcome these drawbacks, many attempts have been made to develop novel controlled drug delivery systems. They can encapsulate the drug and release it to the cancer site without leaking into other sites. The employment of multi-responsive hydrogels as a drug delivery system have some advantages over other drug delivery systems due to their ease of preparation, high efficiency, high-water content, tunable physical, and biological properties. The most advantages of these hydrogels is the volume phase transitions in their cross-linked three-dimensional networks as exposure to external stimuli such as temperature, pH, pressure, electric field, magnetic field and light. There has been research on other drug delivery systems which can respond to changes in pH and temperature for targeted drug release. Among those,gels have been studied mostly for their dual responsiveness. This provides an update on progress of gel based dual pH and temperature responsive drug delivery systems. Various systems under these categories for targeted and controlled delivery of different classes of drugs such as ant diabetic and antibiotic drugs with special emphasis on anticancer drugs are discussed in this review.

Graphical Abstract

A Review on pH and Temperature Responsive Gels in Drug Delivery

Keywords

[1] Luo, Y. L., Zhang, X. Y., Fu, J. Y., Xu, F., & Chen,  Y. S. (2017). Novel temperature and pH dual-sensitive PNIPAM/CMCS/MWCNT semi-IPN nanohybrid hydrogels: Synthesis, characterization, and DOX drug release. International Journal of Polymeric Materials and Polymeric Biomaterials, 66(8), 398-409
[2] Daraee, H., Etemadi, A., Kouhi, M., Alimirzalu, S., & Akbarzadeh, A. (2016). Application of liposomes in medicine and drug delivery. Artificial cells, nanomedicine, and biotechnology, 44(1), 381-391.‏
[3] Biswas, S., Kumari, P., Lakhani, P. M., & Ghosh, B. (2016). Recent advances in polymeric micelles for anti-cancer drug delivery. European Journal of Pharmaceutical Sciences, 83, 184-202.‏
[4] Masood, F. (2016). Polymeric nanoparticles for targeted drug delivery system for cancer therapy. Materials Science and Engineering: C, 60, 569-578.‏
[5] Bardajee, G. R., Mizani, F., & Hosseini, S. S. (2017). pH sensitive release of doxorubicin anticancer drug from gold nanocomposite hydrogel based on poly (acrylic acid) grafted onto salep biopolymer. Journal of Polymer Research, 24(3), 48.‏
[6] Kumar, C. G., & Poornachandra, Y. (2015). Biodirected synthesis of Miconazole-conjugated bacterial silver nanoparticles and their application as antifungal agents and drug delivery vehicles. Colloids and Surfaces B: Biointerfaces, 125, 110-119.‏
[7] Wen, J., Yang, K., Liu, F., Li, H., Xu, Y., & Sun, S. (2017). Diverse gatekeepers for mesoporous silica nanoparticle based drug delivery systems. Chemical Society Reviews, 46(19), 6024-6045.‏
[8] Davaran, S., Ghamkhari, A., Alizadeh, E., Massoumi, B., & Jaymand, M. (2017). Novel dual stimuli-responsive ABC triblock copolymer: RAFT synthesis,“schizophrenic” micellization, and its performance as an anticancer drug delivery nanosystem. Journal of colloid and interface science, 488, 282-293.
[9] Kellum, J. A. (2000). Determinants of blood pH in health and disease. Critical Care, 4(1), 6.
[10] Hanson, D. F. (1997). Fever, temperature, and the immune response. Annals of the New York Academy of Sciences, 813(1), 453-464.
[11] Carlin, K. (2014). Autoimmune disease pH and temperature. Journal of clinical medicine research, 6(4), 305-307.
[12] Cao, Z., Liu, L., & Wang, J. (2010). Effects of pH and Temperature on the Structural and Thermodynamic Character of a-syn12 Peptide in Aqueous Solution. Journal of Biomolecular Structure and Dynamics, 28(3), 343-353.
[13] Bhattacharya, D., Behera, B., Sahu, S. K., Ananthakrishnan, R., Maiti, T. K., & Pramanik, P. (2016). Design of dual stimuli responsive polymer modified magnetic nanoparticles for targeted anti-cancer drug delivery and enhanced MR imaging. New Journal of Chemistry, 40(1), 545-557.
[14] Zhang, L., Guo, R., Yang, M., Jiang, X., & Liu, B. (2007). Thermo and pH dual‐responsive nanoparticles for anti‐cancer drug delivery. Advanced Materials, 19(19), 2988-2992.
[15] Soppimath, K. S., Tan, D. W., & Yang, Y. Y. (2005). pH‐triggered thermally responsive polymer core–shell nanoparticles for drug delivery. Advanced materials, 17(3), 318-323.
[16] Singh, N. K., & Lee, D. S. (2014). In situ gelling pH-and temperature-sensitive biodegradable block copolymer hydrogels for drug delivery. Journal of controlled release, 193, 214-227.
[17] Soppimath, K. S., Aminabhavi, T. M., Dave, A. M., Kumbar, S. G., & Rudzinski, W. E. (2002). Stimulus-responsive “smart” hydrogels as novel drug delivery systems. Drug development and industrial pharmacy, 28(8), 957-974.
[18] Sood, N., Bhardwaj, A., Mehta, S., & Mehta, A. (2016). Stimuli-responsive hydrogels in drug delivery and tissue engineering. Drug delivery, 23(3), 748-770.
[19] Basu, A., Kunduru, K. R., Abtew, E., & Domb, A. J. (2015). Polysaccharide-based conjugates for biomedical applications. Bioconjugate chemistry, 26(8), 1396-1412.‏
[20] Thambi, T., Phan, V. G., & Lee, D. S. (2016). Stimuli‐Sensitive Injectable Hydrogels Based on Polysaccharides and Their Biomedical Applications. Macromolecular rapid communications, 37(23), 1881-1896.
[21] Choi, H. S., Huh, K. M., Ooya, T., & Yui, N. (2003). pH-and thermosensitive supramolecular assembling system: rapidly responsive properties of β-cyclodextrin-conjugated poly (ε-lysine). Journal of the American Chemical Society, 125(21), 6350-6351.
[22] Eljarrat-Binstock, E., Raiskup, F., Stepensky, D., Domb, A. J., & Frucht-Pery, J. (2004). Delivery of gentamicin to the rabbit eye by drug-loaded hydrogel iontophoresis. Investigative ophthalmology & visual science, 45(8), 2543-2548.
[23] Sun, K., Guo, J., He, Y., Song, P., Xiong, Y., & Wang, R. M. (2016). Fabrication of dual-sensitive keratin-based polymer hydrogels and their controllable release behaviors. Journal of Biomaterials science, Polymer edition, 27(18), 1926-1940.
[24] Plamper, F. A., & Richtering, W. (2017). Functional microgels and microgel systems. Accounts of chemical research, 50(2), 131-140.
[25] Li, Z., & Ngai, T. (2013). Microgel particles at the fluid–fluid interfaces. Nanoscale, 5(4), 1399-1410.
[26] Lopez, V. C., Hadgraft, J., & Snowden, M. J. (2005). The use of colloidal microgels as a (Trans) dermal drug delivery system. International journal of pharmaceutics, 292(1-2), 137-147.
[27] T.R. Hoare, D.S. Kohane, Polymer, 49 (2008) 1993.
[28] Andrade-Vivero, P., Fernandez-Gabriel, E., Alvarez-Lorenzo, C., & Concheiro, A. (2007). Improving the loading and release of NSAIDs from pHEMA hydrogels by copolymerization with functionalized monomers. Journal of pharmaceutical sciences96(4), 802-813.
[29] Bos, G. W., Jacobs, J. J., Koten, J. W., Van Tomme, S., Veldhuis, T., van Nostrum, C. F., ... & Hennink, W. E. (2004). In situ crosslinked biodegradable hydrogels loaded with IL-2 are effective tools for local IL-2 therapy. European journal of pharmaceutical sciences21(4), 561-567.
[30] Bouhadir, K. H., Kruger, G. M., Lee, K. Y., & Mooney, D. J. (2000). Sustained and controlled release of daunomycin from cross‐linked poly (aldehyde guluronate) hydrogels. Journal of pharmaceutical sciences89(7), 910-919.
[31] Cai, S., Liu, Y., Shu, X. Z., & Prestwich, G. D. (2005). Injectable glycosaminoglycan hydrogels for controlled release of human basic fibroblast growth factor. Biomaterials26(30), 6054-6067.
[32] Cho, K. Y., Chung, T. W., Kim, B. C., Kim, M. K., Lee, J. H., Wee, W. R., & Cho, C. S. (2003). Release of ciprofloxacin from poloxamer-graft-hyaluronic acid hydrogels in vitro. International journal of pharmaceutics260(1), 83-91.
[33] Galeska, I., Kim, T. K., Patil, S. D., Bhardwaj, U., Chatttopadhyay, D., Papadimitrakopoulos, F., & Burgess, D. J. (2005). Controlled release of dexamethasone from PLGA microspheres embedded within polyacid-containing PVA hydrogels. The AAPS journal7(1), E231-E240.
[34] Liu, J., Lin, S., Li, L., & Liu, E. (2005). Release of theophylline from polymer blend hydrogels. International journal of pharmaceutics298(1), 117-125.
[35] Nishi, K. K., & Jayakrishnan, A. (2007). Self-Gelling Primaquine− Gum Arabic Conjugate: An Injectable Controlled Delivery System for Primaquine. Biomacromolecules8(1), 84-90.
[36] Chen, M. C., Tsai, H. W., Liu, C. T., Peng, S. F., Lai, W. Y., Chen, S. J., ... & Sung, H. W. (2009). A nanoscale drug-entrapment strategy for hydrogel-based systems for the delivery of poorly soluble drugs. Biomaterials30(11), 2102-2111.
[37] Kang, G. D., Cheon, S. H., & Song, S. C. (2006). Controlled release of doxorubicin from thermosensitive poly (organophosphazene) hydrogels. International journal of pharmaceutics319(1-2), 29-36.
[38] Qiao, M., Chen, D., Ma, X., & Liu, Y. (2005). Injectable biodegradable temperature-responsive PLGA–PEG–PLGA copolymers: synthesis and effect of copolymer composition on the drug release from the copolymer-based hydrogels. International Journal of Pharmaceutics294(1-2), 103-112.
[39] Lim, D. W., Nettles, D. L., Setton, L. A., & Chilkoti, A. (2007). Rapid cross-linking of elastin-like polypeptides with (hydroxymethyl) phosphines in aqueous solution. Biomacromolecules8(5), 1463-1470.
[40] Chen, P. (2005). Self-assembly of ionic-complementary peptides: a physicochemical viewpoint. Colloids and Surfaces A: Physicochemical and Engineering Aspects261(1-3), 3-24.
[41] Ito, T., Yeo, Y., Highley, C. B., Bellas, E., Benitez, C. A., & Kohane, D. S. (2007). The prevention of peritoneal adhesions by in situ cross-linking hydrogels of hyaluronic acid and cellulose derivatives. Biomaterials28(6), 975-983.
[42] Luo, Y., Kobler, J. B., Heaton, J. T., Jia, X., Zeitels, S. M., & Langer, R. (2010). Injectable hyaluronic acid‐dextran hydrogels and effects of implantation in ferret vocal fold. Journal of Biomedical Materials Research Part B: Applied Biomaterials93(2), 386-393.
[43] Elbert, D. L., Pratt, A. B., Lutolf, M. P., Halstenberg, S., & Hubbell, J. A. (2001). Protein delivery from materials formed by self-selective conjugate addition reactions. Journal of Controlled Release76(1-2), 11-25.
[44] Popescu, M. T., Mourtas, S., Pampalakis, G., Antimisiaris, S. G., & Tsitsilianis, C. (2011). pH-responsive hydrogel/liposome soft nanocomposites for tuning drug release. Biomacromolecules12(8), 3023-3030.
[45] Baumann, M. D., Kang, C. E., Tator, C. H., & Shoichet, M. S. (2010). Intrathecal delivery of a polymeric nanocomposite hydrogel after spinal cord injury. Biomaterials31(30), 7631-7639.
[46] Baumann, M. D., Kang, C. E., Stanwick, J. C., Wang, Y., Kim, H., Lapitsky, Y., & Shoichet, M. S. (2009). An injectable drug delivery platform for sustained combination therapy. Journal of Controlled Release138(3), 205-213.
[47] Bernardo, M. V., Blanco, M. D., Olmo, R., & Teijón, J. M. (2002). Delivery of bupivacaine included in poly (acrylamide‐co‐monomethyl itaconate) hydrogels as a function of the pH swelling medium. Journal of applied polymer science86(2), 327-334.
[48] Gordijo, C. R., Koulajian, K., Shuhendler, A. J., Bonifacio, L. D., Huang, H. Y., Chiang, S., ... & Wu, X. Y. (2011). Nanotechnology‐enabled closed loop insulin delivery device: In vitro and in vivo evaluation of glucose‐regulated insulin release for diabetes control. Advanced Functional Materials21(1), 73-82.
[49] Hirakura, T., Yasugi, K., Nemoto, T., Sato, M., Shimoboji, T., Aso, Y., ... & Akiyoshi, K. (2010). Hybrid hyaluronan hydrogel encapsulating nanogel as a protein nanocarrier: new system for sustained delivery of protein with a chaperone-like function. Journal of Controlled Release142(3), 483-489.
[50] Musch, J., Schneider, S., Lindner, P., & Richtering, W. (2008). Unperturbed volume transition of thermosensitive poly-(n-isopropylacrylamide) microgel particles embedded in a hydrogel matrix. The Journal of Physical Chemistry B112(20), 6309-6314.
[51] Hoare, T., Sivakumaran, D., Stefanescu, C. F., Lawlor, M. W., & Kohane, D. S. (2012). Nanogel scavengers for drugs: Local anesthetic uptake by thermoresponsive nanogels. Acta biomaterialia8(4), 1450-1458.
[52] Chen, P. C., Kohane, D. S., Park, Y. J., Bartlett, R. H., Langer, R., & Yang, V. C. (2004). Injectable microparticle–gel system for prolonged and localized lidocaine release. II. In vivo anesthetic effects. Journal of Biomedical Materials Research Part A: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials70(3), 459-466..
[53] McGillicuddy, F. C., Lynch, I., Rochev, Y. A., Burke, M., Dawson, K. A., Gallagher, W. M., & Keenan, A. K. (2006). Novel “plum pudding” gels as potential drug‐eluting stent coatings: Controlled release of fluvastatin. Journal of Biomedical Materials Research Part A79(4), 923-933.
[54] Lynch, I., de Gregorio, P., & Dawson, K. A. (2005). Simultaneous release of hydrophobic and cationic solutes from thin-film “plum-pudding” gels: a multifunctional platform for surface drug delivery?. The Journal of Physical Chemistry B109(13), 6257-6261.
[55] Sivakumaran, D., Maitland, D., & Hoare, T. (2011). Injectable microgel-hydrogel composites for prolonged small-molecule drug delivery. Biomacromolecules12(11), 4112-4120.
[56] Yeo, Y., Ito, T., Bellas, E., Highley, C. B., Marini, R., & Kohane, D. S. (2007). In situ cross-linkable hyaluronan hydrogels containing polymeric nanoparticles for preventing postsurgical adhesions. Annals of surgery245(5), 819.
[57] Panayiotou, M., Pöhner, C., Vandevyver, C., Wandrey, C., Hilbrig, F., & Freitag, R. (2007). Synthesis and characterisation of thermo-responsive poly (N, N′-diethylacrylamide) microgels. Reactive and Functional Polymers67(9), 807-819.
[58] Lynch, I., & Dawson, K. A. (2004). Release of model compounds from “plum-pudding”-type gels composed of microgel particles randomly dispersed in a gel matrix. The Journal of Physical Chemistry B108(30), 10893-10898.
[59] Meid, J., Friedrich, T., Tieke, B., Lindner, P., & Richtering, W. (2011). Composite hydrogels with temperature sensitive heterogeneities: influence of gel matrix on the volume phase transition of embedded poly-(N-isopropylacrylamide) microgels. Physical Chemistry Chemical Physics13(8), 3039-3047..
[60] Lynch, I., & Dawson, K. A. (2003). Synthesis and characterization of an extremely versatile structural motif called the “Plum-Pudding” gel. The Journal of Physical Chemistry B107(36), 9629-9637.
[61] Galaev, I. Y., Dainiak, M. B., Plieva, F., & Mattiasson, B. (2007). Effect of matrix elasticity on affinity binding and release of bioparticles. Elution of bound cells by temperature-induced shrinkage of the smart macroporous hydrogel. Langmuir23(1), 35-40.
[62] Xia, L. W., Ju, X. J., Liu, J. J., Xie, R., & Chu, L. Y. (2010). Responsive hydrogels with poly (N-isopropylacrylamide-co-acrylic acid) colloidal spheres as building blocks. Journal of colloid and interface science349(1), 106-113.
[63] Nigro, V., Angelini, R., Bertoldo, M., Bruni, F., Castelvetro, V., Ricci, M. A., ... & Ruzicka, B. (2015). Local structure of temperature and pH-sensitive colloidal microgels. The Journal of chemical physics143(11), 114904.
[64] Hayati, M., Bardajee, G. R., Ramezani, M., Hosseini, S. S., & Mizani, F. (2019). Temperature/pH/magnetic triple sensitive nanogel‐hydrogel nanocomposite for release of anticancer drug. Polymer International.
[65] Bardajee, G. R., Hosseini, S. S., & Ghavami, S. (2018). Embedded of Nanogel into Multi-responsive Hydrogel Nanocomposite for Anticancer Drug Delivery. Journal of Inorganic and Organometallic Polymers and Materials28(6), 2196-2205.
[66] Sivakumaran, D., Maitland, D., Oszustowicz, T., & Hoare, T. (2013). Tuning drug release from smart microgel–hydrogel composites via cross-linking. Journal of colloid and interface science392, 422-430.
[67] Sivakumaran, D., Maitland, D., & Hoare, T. (2011). Injectable microgel-hydrogel composites for prolonged small-molecule drug delivery. Biomacromolecules, 12(11), 4112-4120.
[68] Kleinen, J., & Richtering, W. (2011). Rearrangements in and release from responsive microgel− polyelectrolyte complexes induced by temperature and time. The Journal of Physical Chemistry B, 115(14), 3804-3810.
[69] Kleinen, J., Klee, A., & Richtering, W. (2010). Influence of architecture on the interaction of negatively charged multisensitive poly (N-isopropylacrylamide)-co-methacrylic acid microgels with oppositely charged polyelectrolyte: absorption vs adsorption. Langmuir, 26(13), 11258-11265
[70] Lehmann, S., Seiffert, S., & Richtering, W. (2012). Spatially resolved tracer diffusion in complex responsive hydrogels. Journal of the American Chemical Society, 134(38), 15963-15969.
[71] Karnoosh-Yamchi, J., Mobasseri, M., Akbarzadeh, A., Davaran, S., Ostad-Rahimi, A. R., Hamishehkar, H., & Rahmati-Yamchi, M. (2014). Preparation of pH sensitive insulin-loaded Nano hydrogels and evaluation of insulin releasing in different pH conditions. Molecular biology reports, 41(10), 6705-6712.
[72] Rao, K. M., Rao, K. K., Ramanjaneyulu, G., & Ha, C. S. (2015). Curcumin encapsulated pH sensitive gelatin based interpenetrating polymeric network nanogels for anti-cancer drug delivery. International journal of pharmaceutics, 478(2), 788-795
[73] Xiong, W., Wang, W., Wang, Y., Zhao, Y., Chen, H., Xu, H., & Yang, X. (2011). Dual temperature/pH-sensitive drug delivery of poly (N-isopropylacrylamide-co-acrylic acid) nanogels conjugated with doxorubicin for potential application in tumor hyperthermia therapy. Colloids and Surfaces B: Biointerfaces, 84(2), 447-453.
[74] Peng, J., Qi, T., Liao, J., Chu, B., Yang, Q., Li, W., & Qian, Z. (2013). Controlled release of cisplatin from pH-thermal dual responsive nanogels. Biomaterials, 34(34), 8726-8740.
[75] Rao, K. M., Mallikarjuna, B., Rao, K. K., Siraj, S., Rao, K. C., & Subha, M. C. S. (2013). Novel thermo/pH sensitive nanogels composed from poly (N-vinylcaprolactam) for controlled release of an anticancer drug. Colloids and Surfaces B: Biointerfaces, 102, 891-897.
[76] Demirel, G. B., & von Klitzing, R. (2013). A new multiresponsive drug delivery system using smart nanogels. ChemPhysChem, 14(12), 2833-2840.
[77] Bardajee, G. R., Hooshyar, Z., Farsi, M., Mobini, A., & Sang, G. (2017). Synthesis of a novel thermo/pH sensitive nanogel based on salep modified graphene oxide for drug release. Materials Science and Engineering: C, 72, 558-565.
[78] Zhou, N., Cao, X., Du, X., Wang, H., Wang, M., Liu, S., & Xu, B. (2017). Hyper‐Crosslinkers Lead to Temperature‐and pH‐Responsive Polymeric Nanogels with Unusual Volume Change. Angewandte Chemie, 129(10), 2667-2671.