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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Review Article

Application of Thermoresponsive Smart Polymers based in situ Gel as a Novel Carrier for Tumor Targeting

Author(s): Nidhi Sudhir Dhote, Rajat Dineshbhai Patel, Utkarsha Kuwar, Mukta Agrawal, Amit Alexander, Parag Jain and Ajazuddin*

Volume 24, Issue 4, 2024

Published on: 06 September, 2023

Page: [375 - 396] Pages: 22

DOI: 10.2174/1568009623666230803111718

Price: $65

Abstract

The temperature-triggered in situ gelling system has been revolutionized by introducing an intelligent polymeric system. Temperature-triggered polymer solutions are initially in a sol state and then undergo a phase transition to form a gel at body temperature due to various parameters like pH, temperature, and so on. These smart polymers offer a number of advantages, including ease of administration, long duration of release of the drug, low administration frequency with good patient compliance, and targeted drug delivery with fewer adverse effects. Polymers such as poly(N-isopropylacrylamide) (PNIPAAm), polyethylene glycol (PEG), poly (N, N′-diethyl acrylamide), and polyoxypropylene (PPO) have been briefly discussed. In addition to various novel Drug Delivery Systems (DDS), the smart temperature-triggered polymeric system has various applications in cancer therapy and many other disease conditions. This review focuses on the principals involved in situ gelling systems using various temperature-triggered polymers for chemotherapeutic purposes, using smart DDS, and their advanced application in cancer therapy, as well as available marketed formulations and recent advances in these thermoresponsive sol-gel transforming systems.

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[1]
Maeda, H.; Khatami, M. Analyses of repeated failures in cancer therapy for solid tumors: poor tumor-selective drug delivery, low therapeutic efficacy and unsustainable costs. Clin Transl Med., 2018, 7(1), 11.
[http://dx.doi.org/10.1186/s40169-018-0185-6]
[2]
Parsa, N. Environmental factors inducing human cancers. Iran J Publ Heal., 2012, 41(11), 1.
[3]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[4]
Mao, Y.; Li, X.; Chen, G.; Wang, S. Thermosensitive hydrogel system with paclitaxel liposomes used in localized drug delivery system for in situ treatment of tumor: better antitumor efficacy and lower toxicity. J. Pharm. Sci., 2016, 105(1), 194-204.
[http://dx.doi.org/10.1002/jps.24693] [PMID: 26580704]
[5]
Thakur, R.; Sharma, A. An overview of mucoadhesive thermoreversible nasal gel. As J Pharm Res Develop., 2021, 9(4), 158-168.
[6]
Madan, M.; Bajaj, A.; Lewis, S.; Udupa, N.; Baig, J.A. In situ forming polymeric drug delivery systems. Indian J. Pharm. Sci., 2009, 71(3), 242-251.
[http://dx.doi.org/10.4103/0250-474X.56015] [PMID: 20490289]
[7]
Gao, S.; Tang, G.; Hua, D.; Xiong, R.; Han, J.; Jiang, S.; Zhang, Q.; Huang, C. Stimuli-responsive bio-based polymeric systems and their applications. J. Mater. Chem. B Mater. Biol. Med., 2019, 7(5), 709-729.https://pubs.rsc.org/en/content/articlehtml/2019/tb/c8tb02491j
[http://dx.doi.org/10.1039/C8TB02491J] [PMID: 32254845]
[8]
Karimi, M.; Sahandi Zangabad, P.; Ghasemi, A.; Amiri, M.; Bahrami, M.; Malekzad, H.; Ghahramanzadeh Asl, H.; Mahdieh, Z.; Bozorgomid, M.; Ghasemi, A.; Rahmani Taji Boyuk, M.R.; Hamblin, M.R. Temperature-responsive smart nanocarriers for delivery of therapeutic agents: Applications and recent advances. ACS Appl. Mater. Interfaces, 2016, 8(33), 21107-21133.
[http://dx.doi.org/10.1021/acsami.6b00371] [PMID: 27349465]
[9]
Wei, W.; Li, H.; Yin, C.; Tang, F. Research progress in the application of in situ hydrogel system in tumor treatment. Drug Deliv., 2020, 27(1), 460-468.
[http://dx.doi.org/10.1080/10717544.2020.1739171]
[10]
Das, SS; Bharadwaj, P; Bilal, M; Barani, M; Rahdar, A; Taboada, P Stimuli-responsive polymeric nanocarriers for drug delivery, imaging, and theragnosis. Polymers., 2020, 12(6), 1397.
[11]
Li, C.; Wang, J.; Wang, Y.; Gao, H.; Wei, G.; Huang, Y.; Yu, H.; Gan, Y.; Wang, Y.; Mei, L.; Chen, H.; Hu, H.; Zhang, Z.; Jin, Y. Recent progress in drug delivery. Acta Pharm. Sin. B, 2019, 9(6), 1145-1162.
[http://dx.doi.org/10.1016/j.apsb.2019.08.003] [PMID: 31867161]
[12]
Yadav, P.; Jain, J.; Sherje, A.P. Recent advances in nanocarriers-based drug delivery for cancer therapeutics: A review. React. Funct. Polym., 2021, 165, 104970.
[http://dx.doi.org/10.1016/j.reactfunctpolym.2021.104970]
[13]
Oleszko-Torbus, N.; Mendrek, B.; Kowalczuk, A.; Wałach, W.; Trzebicka, B.; Utrata-Wesołek, A. The role of polymer structure in formation of various nano- and microstructural materials: 30 years of research in the laboratory of nano- and microstructural materials at the centre of polymer and carbon materials PAS. Polymer, 2021, 13(17), 2892.
[14]
Hennink, W.E.; van Nostrum, C.F. Novel crosslinking methods to design hydrogels. Adv. Drug Deliv. Rev., 2012, 64(Suppl.), 223-236.
[http://dx.doi.org/10.1016/j.addr.2012.09.009] [PMID: 11755704]
[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]
Jain, D.; Kumar, V.; Singh, S.; Mullertz, A.; Bar-Shalom, D. Newer trends in in situ gelling systems for controlled ocular drug delivery. J. Anal. Pharm. Res., 2016, 2(3), 00022.
[http://dx.doi.org/10.15406/japlr.2016.02.00022]
[17]
Hogan, K.J.; Mikos, A.G. Biodegradable thermoresponsive polymers: Applications in drug delivery and tissue engineering. Polymer, 2020, 211, 123063.
[http://dx.doi.org/10.1016/j.polymer.2020.123063]
[18]
Review, A. Nanocellulose applications for drug delivery: A review. J. Environ. Sci., 2019, 35(3), 141-149.
[19]
Liu, H.; Rong, L.; Wang, B.; Xie, R.; Sui, X.; Xu, H.; Zhang, L.; Zhong, Y.; Mao, Z. Facile fabrication of redox/pH dual stimuli responsive cellulose hydrogel. Carbohydr. Polym., 2017, 176, 299-306.
[http://dx.doi.org/10.1016/j.carbpol.2017.08.085] [PMID: 28927612]
[20]
Chen, W.; He, H.; Zhu, H.; Cheng, M.; Li, Y.; Wang, S. Thermo-responsive cellulose-based material with switchable wettability for controllable oil/water separation. Polymers, 2018, 10(6), 592.
[http://dx.doi.org/10.3390/polym10060592] [PMID: 30966626]
[21]
Zhang, L.K.; Du, S.; Wang, X.; Jiao, Y.; Yin, L.; Zhang, Y.; Guan, Y-Q. Bacterial cellulose based composites enhanced transdermal drug targeting for breast cancer treatment. Chem. Eng. J., 2019, 370, 749-759.
[http://dx.doi.org/10.1016/j.cej.2019.03.216]
[22]
Capanema, N.S.V.; Mansur, A.A.P.; Carvalho, S.M.; Carvalho, I.C.; Chagas, P.; de Oliveira, L.C.A.; Mansur, H.S. Bioengineered carboxymethyl cellulose-doxorubicin prodrug hydrogels for topical chemotherapy of melanoma skin cancer. Carbohydr. Polym., 2018, 195, 401-412.
[http://dx.doi.org/10.1016/j.carbpol.2018.04.105] [PMID: 29804993]
[23]
Omidi, S.; Pirhayati, M.; Kakanejadifard, A. Co-delivery of doxorubicin and curcumin by a pH-sensitive, injectable, and in situ hydrogel composed of chitosan, graphene, and cellulose nanowhisker. Carbohydr. Polym., 2020, 231, 115745.
[http://dx.doi.org/10.1016/j.carbpol.2019.115745] [PMID: 31888811]
[24]
Yusefi, M.; Lee-Kiun, M.S.; Shameli, K.; Teow, S.Y.; Ali, R.R.; Siew, K.K.; Chan, H.Y.; Wong, M.M.T.; Lim, W.L.; Kuča, K. 5-Fluorouracil loaded magnetic cellulose bionanocomposites for potential colorectal cancer treatment. Carbohydr. Polym., 2021, 273, 118523.
[http://dx.doi.org/10.1016/j.carbpol.2021.118523] [PMID: 34560940]
[25]
Mandal, B.; Rameshbabu, A.P.; Soni, S.R.; Ghosh, A.; Dhara, S.; Pal, S. In situ silver nanowire deposited cross-linked carboxymethyl cellulose: A potential transdermal anticancer drug carrier. ACS Appl. Mater. Interfaces, 2017, 9(42), 36583-36595.
[http://dx.doi.org/10.1021/acsami.7b10716] [PMID: 28948779]
[]
26) Argüelles-Monal, W.; Recillas-Mota, M.; Fernández-Quiroz, D. Chitosan-based thermosensitive materials In: Biological activities and application of marine polysaccharides; Shalaby E.A., Ed.; InTech: 2017; pp.279-302.
[27]
Kurakula, M.; Raghavendra Naveen, N. In situ gel loaded with chitosan-coated simvastatin nanoparticles: Promising delivery for effective anti-proliferative activity against Tongue carcinoma. Mar Drugs., 2020, 18, 201.
[28]
Li, R.; Lin, Z.; Zhang, Q.; Zhang, Y.; Liu, Y.; Lyu, Y.; Li, X.; Zhou, C.; Wu, G.; Ao, N.; Li, L. Injectable and in situ-formable thiolated chitosan-coated liposomal hydrogels as curcumin carriers for prevention of in vivo breast cancer recurrence. ACS Appl. Mater. Interfaces, 2020, 12(15), 17936-17948.
[http://dx.doi.org/10.1021/acsami.9b21528] [PMID: 32208630]
[29]
Giacone, D.V.; Dartora, V.F.M.C.; de Matos, J.K.R.; Passos, J.S.; Miranda, D.A.G.; de Oliveira, E.A.; Silveira, E.R.; Costa-Lotufo, L.V.; Maria-Engler, S.S.; Lopes, L.B. Effect of nanoemulsion modification with chitosan and sodium alginate on the topical delivery and efficacy of the cytotoxic agent piplartine in 2D and 3D skin cancer models. Int. J. Biol. Macromol., 2020, 165(Pt A), 1055-1065.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.09.167] [PMID: 32987080]
[30]
Kim, S.; Nishimoto, S.K.; Bumgardner, J.D.; Haggard, W.O.; Gaber, M.W.; Yang, Y. A chitosan/β-glycerophosphate thermo-sensitive gel for the delivery of ellagic acid for the treatment of brain cancer. Biomaterials, 2010, 31(14), 4157-4166.
[http://dx.doi.org/10.1016/j.biomaterials.2010.01.139] [PMID: 20185170]
[31]
Khan, S.; Akhtar, N.; Minhas, M.U.; Badshah, S.F. pH/Thermo-dual responsive tunable in situ cross-linkable depot injectable hydrogels based on poly(N-Isopropylacrylamide)/carboxymethyl chitosan with potential of controlled localized and systemic drug delivery. AAPS PharmSciTech, 2019, 20(3), 119.
[http://dx.doi.org/10.1208/s12249-019-1328-9] [PMID: 30790143]
[32]
Turabee, M.H.; Jeong, T.H.; Ramalingam, P.; Kang, J.H.; Ko, Y.T. N,N,N-trimethyl chitosan embedded in situ Pluronic F127 hydrogel for the treatment of brain tumor. Carbohydr. Polym., 2019, 203, 302-309.
[http://dx.doi.org/10.1016/j.carbpol.2018.09.065] [PMID: 30318217]
[33]
Jamal, A.; Shahzadi, L.; Ahtzaz, S.; Zahid, S.; Chaudhry, A.A.; Rehman, I.; Yar, M. Identification of anti-cancer potential of doxazocin: Loading into chitosan based biodegradable hydrogels for on-site delivery to treat cervical cancer. Mater. Sci. Eng. C, 2018, 82(82), 102-109.
[http://dx.doi.org/10.1016/j.msec.2017.08.054] [PMID: 29025638]
[34]
Chatterjee, S; Hui, PCL Thermoresponsive hydrogels and their biomedical applications: special insight into their applications in textile based transdermal therapy. Polymers., 2018, 10(5), 480.
[35]
Jahanban-Esfahlan, R.; Derakhshankhah, H.; Haghshenas, B.; Massoumi, B.; Abbasian, M.; Jaymand, M. A bio-inspired magnetic natural hydrogel containing gelatin and alginate as a drug delivery system for cancer chemotherapy. Int. J. Biol. Macromol., 2020, 156, 438-445.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.04.074] [PMID: 32298719]
[36]
Tashi, Z.; Zare, M.; Parvin, N. Application of phytic-acid as an in-situ crosslinking agent in electrospun gelatin-based scaffolds for skin tissue engineering. Mater. Lett., 2020, 264, 127275.
[http://dx.doi.org/10.1016/j.matlet.2019.127275]
[37]
Fan, Z.; Cheng, P.; Yin, G.; Wang, Z.; Han, J. In situ forming oxidized salecan/gelatin injectable hydrogels for vancomycin delivery and 3D cell culture. J. Biomater. Sci. Polym. Ed., 2020, 31(6), 762-780.
[http://dx.doi.org/10.1080/09205063.2020.1717739] [PMID: 31944896]
[38]
Nazeri, M.T.; Javanbakht, S.; Shaabani, A.; Ghorbani, M. 5-aminopyrazole-conjugated gelatin hydrogel: A controlled 5-fluorouracil delivery system for rectal administration. J. Drug Deliv. Sci. Technol., 2020, 57, 101669.
[http://dx.doi.org/10.1016/j.jddst.2020.101669]
[39]
Pham, T.N.; Su, C.F.; Huang, C.C.; Jan, J.S. Biomimetic hydrogels based on L-Dopa conjugated gelatin as pH-responsive drug carriers and antimicrobial agents. Colloids Surf. B Biointerfaces, 2020, 196, 111316.
[http://dx.doi.org/10.1016/j.colsurfb.2020.111316] [PMID: 32827950]
[40]
Dutta, P.; Giri, S. and Giri, T.K. Xyloglucan as green renewable biopolymer used in drug delivery and tissue engineering. Int. J. Biol. Macromol., 2020, 160, 55-68.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.05.148]
[41]
Fathi, M.; Alami-Milani, M.; Geranmayeh, M.H.; Barar, J.; Erfan-Niya, H.; Omidi, Y. Dual thermo-and pH-sensitive injectable hydrogels of chitosan/(poly(N-isopropylacrylamide-co-itaconic acid)) for doxorubicin delivery in breast cancer. Int. J. Biol. Macromol., 2019, 128, 957-964.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.01.122] [PMID: 30685304]
[42]
Xu, X.; Liu, Y.; Fu, W.; Yao, M.; Ding, Z.; Xuan, J.; Li, D.; Wang, S.; Xia, Y. and Cao, M. Poly (N-isopropylacrylamide)-based thermoresponsive composite hydrogels for biomedical applications. Polymers, 2020, 12(3), 580.
[43]
Eskandari, P.; Abousalman-Rezvani, Z.; Hajebi, S.; Roghani-Mamaqani, H.; Salami-Kalajahi, M. Controlled release of anti-cancer drug from the shell and hollow cavities of poly(N-isopropylacrylamide) hydrogel particles synthesized via reversible addition-fragmentation chain transfer polymerization. Eur. Polym. J., 2020, 135, 109877.
[http://dx.doi.org/10.1016/j.eurpolymj.2020.109877]
[44]
Farboudi, A; Nouri, A; Shirinzad, S; Sojoudi, P; Davaran, S; Akrami, M Synthesis of magnetic gold coated poly (ε-caprolactonediol) based polyurethane/poly(N-isopropylacrylamide)-grafted-chitosan core-shell nanofibers for controlled release of paclitaxel and 5-FU. Int J Biol Macromol., 2020, 150, 1130-1140.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.10.120]
[45]
Hajebi, S.; Abdollahi, A.; Roghani-Mamaqani, H.; Salami-Kalajahi, M. Temperature-responsive poly(N-isopropylacrylamide) nanogels: The role of hollow cavities and different shell cross-linking densities on doxorubicin loading and release. Langmuir, 2020, 36(10), 2683-2694.
[http://dx.doi.org/10.1021/acs.langmuir.9b03892] [PMID: 32130018]
[46]
Singh, B.; Khurana, R.K.; Garg, B.; Saini, S.; Kaur, R. Stimuli-responsive systems with diverse drug delivery and biomedical applications: Recent updates and mechanistic pathways. Crit. Rev. Ther. Drug Carrier Syst., 2017, 34(3), 209-255.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2017017284] [PMID: 28845760]
[47]
Kaamyabi, S.; Habibi, D.; Amini, M.M. Preparation and characterization of the pH and thermosensitive magnetic molecular imprinted nanoparticle polymer for the cancer drug delivery. Bioorg. Med. Chem. Lett., 2016, 26(9), 2349-2354.
[http://dx.doi.org/10.1016/j.bmcl.2016.03.020] [PMID: 27020717]
[48]
Liang, M.; Yang, T.M.; Chang, H.P.; Wang, Y.M. Dual-responsive polymer–drug nanoparticles for drug delivery. React. Funct. Polym., 2015, 86, 27-36.
[http://dx.doi.org/10.1016/j.reactfunctpolym.2014.11.006]
[49]
Wang, X.; Li, M.; Hou, Y.; Li, Y.; Yao, X.; Xue, C.; Fei, Y.; Xiang, Y.; Cai, K.; Zhao, Y.; Luo, Z. Tumor-microenvironment-activated in situ self-assembly of sequentially responsive biopolymer for targeted photodynamic therapy. Adv. Funct. Mater., 2020, 30(40), 2000229.
[http://dx.doi.org/10.1002/adfm.202000229]
[50]
Lima-Sousa, R.; de Melo-Diogo, D.; Alves, C.G.; Cabral, C.S.D.; Miguel, S.P.; Mendonça, A.G.; Correia, I.J. Injectable in situ forming thermo-responsive graphene based hydrogels for cancer chemo-photothermal therapy and NIR light-enhanced antibacterial applications. Mater. Sci. Eng. C, 2020, 117(July), 111294.
[http://dx.doi.org/10.1016/j.msec.2020.111294] [PMID: 32919655]
[51]
Zhu, X.; Gong, Y.; Liu, Y.; Yang, C.; Wu, S.; Yuan, G.; Guo, X.; Liu, J.; Qin, X. Ru@CeO2 yolk shell nanozymes: Oxygen supply in situ enhanced dual chemotherapy combined with photothermal therapy for orthotopic/subcutaneous colorectal cancer. Biomaterials, 2020, 242(February), 119923.
[http://dx.doi.org/10.1016/j.biomaterials.2020.119923] [PMID: 32145506]
[52]
Gautam, M.; Kumar Poudel, B.; Chi Soe, Z.; Poudel, K.; Maharjan, S.; Kwang Ku, S.; Soon Yong, C.; Woo Joo, S.; Oh Kim, J.; Hoon Byeon, J. Facile processing for instant production of clinically-approvable nanoagents for combination cancer therapy. Chem. Eng. J., 2020, 383(October), 123177.
[http://dx.doi.org/10.1016/j.cej.2019.123177]
[53]
Tan, S.; Zou, C.; Zhang, W.; Yin, M.; Gao, X.; Tang, Q. Recent developments in D -α-tocopheryl polyethylene glycol-succinate-based nanomedicine for cancer therapy. Drug Deliv., 2017, 24(1), 1831-1842.
[http://dx.doi.org/10.1080/10717544.2017.1406561] [PMID: 29182031]
[54]
Ko, N.R.; Hong, S.H.; Nafiujjaman, M.; An, S.Y.; Revuri, V.; Lee, S.J.; Kwon, I.K.; Lee, Y.; Oh, S.J. Glutathione-responsive PEGylated GQD-based nanomaterials for diagnosis and treatment of breast cancer. J. Ind. Eng. Chem., 2019, 71, 301-307.
[http://dx.doi.org/10.1016/j.jiec.2018.11.039]
[55]
Wu, Z.; Zou, X.; Yang, L.; Lin, S.; Fan, J.; Yang, B.; Sun, X.; Wan, Q.; Chen, Y.; Fu, S. Thermosensitive hydrogel used in dual drug delivery system with paclitaxel-loaded micelles for in situ treatment of lung cancer. Colloids Surf. B Biointerfaces, 2014, 122(122), 90-98.
[http://dx.doi.org/10.1016/j.colsurfb.2014.06.052] [PMID: 25033428]
[56]
Xu, N.; Huang, X.; Yin, G.; Bu, M.; Pu, X.; Chen, X.; Liao, X.; Huang, Z. Thermosensitive star polymer pompons with a core–arm structure as thermo-responsive controlled release drug carriers. RSC Advances, 2018, 8(28), 15604-15612.
[http://dx.doi.org/10.1039/C8RA02117A] [PMID: 35539452]
[57]
Chandra, S.; Noronha, G.; Dietrich, S.; Lang, H.; Bahadur, D. Dendrimer-magnetic nanoparticles as multiple stimuli responsive and enzymatic drug delivery vehicle. J. Magn. Magn. Mater., 2015, 380, 7-12.
[http://dx.doi.org/10.1016/j.jmmm.2014.10.096]
[58]
Kasza, G.; Stumphauser, T.; Bisztrán, M.; Szarka, G.; Hegedüs, I.; Nagy, E.; Iván, B. Thermoresponsive poly(N,n-diethylacrylamide-co-glycidyl methacrylate) copolymers and its catalytically active α-chymotrypsin bioconjugate with enhanced enzyme stability. Polymers, 2021, 13(6), 987.
[http://dx.doi.org/10.3390/polym13060987] [PMID: 33806995]
[59]
Işıklan, N.; Tokmak, Ş. Development of thermo/pH-responsive chitosan coated pectin-graft-poly(N,N-diethyl acrylamide) microcarriers. Carbohydr. Polym., 2019, 218(April), 112-125.
[http://dx.doi.org/10.1016/j.carbpol.2019.04.068] [PMID: 31221312]
[60]
Xie, M.H.; Ge, M.; Peng, J.B.; Jiang, X.R.; Wang, D.S.; Ji, L.Q.; Ying, Y.; Wang, Z. In-vivo anti-tumor activity of a novel poloxamer-based thermosensitive in situ gel for sustained delivery of norcantharidin. Pharm. Dev. Technol., 2019, 24(5), 623-629.
[http://dx.doi.org/10.1080/10837450.2018.1550788] [PMID: 30457414]
[61]
Chung, C.K.; García-Couce, J.; Campos, Y.; Kralisch, D.; Bierau, K.; Chan, A.; Ossendorp, F.; Cruz, L.J. Doxorubicin loaded poloxamer thermosensitive hydrogels: Chemical, pharmacological and biological evaluation. Molecules, 2020, 25(9), 2219.
[http://dx.doi.org/10.3390/molecules25092219] [PMID: 32397328]
[62]
Ci, L; Huang, Z; Lv, F; Wang, J; Feng, L; Sun, F. Enhanced delivery of imatinib into vaginal mucosa via a new positively charged nanocrystal-loaded in situ hydrogel formulation for treatment of cervical cancer. Pharmaceutics., 2019, 11(1), 15.
[http://dx.doi.org/10.3390/pharmaceutics11010015]
[63]
Zambanini, T.; Borges, R.; de Souza, A.C.S.; Justo, G.Z.; Machado, J., Jr; de Araujo, D.R.; Marchi, J. Holmium-containing bioactive glasses dispersed in poloxamer 407 hydrogel as a theragenerative composite for bone cancer treatment. Materials, 2021, 14(6), 1459.
[http://dx.doi.org/10.3390/ma14061459] [PMID: 33802678]
[64]
Li, Z.; Chen, L.; He, C.; Han, Y.; Han, M.; Zhang, Y.; Qi, L.; Xing, X.; Huang, W.; Gao, Z.; Xing, J. Improving anti-tumor outcomes for colorectal cancer therapy through in situ thermosensitive gel loading harmine. Am. J. Transl. Res., 2020, 12(5), 1658-1671.
[PMID: 32509167]
[65]
Zhang, Z.; Li, A.; Min, X.; Zhang, Q.; Yang, J.; Chen, G.; Zou, M.; Sun, W.; Cheng, G. An ROS-sensitive tegafur-PpIX-heterodimer-loaded in situ injectable thermosensitive hydrogel for photodynamic therapy combined with chemotherapy to enhance the tegafur-based treatment of breast cancer. Biomater. Sci., 2021, 9(1), 221-237.
[http://dx.doi.org/10.1039/D0BM01519A] [PMID: 33179659]
[66]
Georgiadis, D. Tetronic acids. Natural lactones and lactams: Synt. Occur. Biol. Act., 2013, pp.1-49.
[67]
Patidar, P.; Pillai, S.A.; Sheth, U.; Bahadur, P.; Bahadur, A. Glucose triggered enhanced solubilisation, release and cytotoxicity of poorly water soluble anti-cancer drugs fromT1307 micelles. J. Biotechnol., 2017, 254(May), 43-50.
[http://dx.doi.org/10.1016/j.jbiotec.2017.06.013] [PMID: 28624378]
[68]
Rey-Rico, A.; Cucchiarini, M. PEO-PPO-PEO tri-block copolymers for gene delivery applications in human regenerative medicine—an overview. Int. J. Mol. Sci., 2018, 19(3), 775.
[http://dx.doi.org/10.3390/ijms19030775] [PMID: 29518011]
[69]
Cagel, M; Moretton, MA; Bernabeu, E; Zubillaga, M; Lagomarsino, E; Vanzulli, S Antitumor efficacy and cardiotoxic effect of doxorubicin-loaded mixed micelles in 4T1 murine breast cancer model. Comparative studies using Doxil® and free doxorubicin. J Drug Deliv Sci Technol, 2020, 56, 101506.
[http://dx.doi.org/10.1016/j.jddst.2020.101506]
[70]
Kim, B.Y.; Bae, J.W.; Park, K.D. Enzymatically in situ shell cross-linked micelles composed of 4-arm PPO–PEO and heparin for controlled dual drug delivery. J. Control. Release, 2013, 172(2), 535-540.
[http://dx.doi.org/10.1016/j.jconrel.2013.05.003] [PMID: 23680287]
[71]
Bearat, H.H.; Vernon, B.L. Environmentally responsive injectable materials. Inj. Biomater., 2011, 263-297.
[72]
Fu, H.; Huang, L.; Xu, C.; Zhang, J.; Li, D.; Ding, L.; Liu, L.; Dong, Y.; Wang, W.; Duan, Y. Highly biocompatible thermosensitive nanocomposite gel for combined therapy of hepatocellular carcinoma via the enhancement of mitochondria related apoptosis. Nanomedicine, 2019, 21, 102062.
[http://dx.doi.org/10.1016/j.nano.2019.102062] [PMID: 31344501]
[73]
Wang, D.; Zhang, S.; Zhang, T.; Wan, G.; Chen, B.; Xiong, Q.; Zhang, J.; Zhang, W.; Wang, Y. Pullulan-coated phospholipid and Pluronic F68 complex nanoparticles for carrying IR780 and paclitaxel to treat hepatocellular carcinoma by combining photothermal therapy/photodynamic therapy and chemotherapy. Int. J. Nanomedicine, 2017, 12, 8649-8670.
[http://dx.doi.org/10.2147/IJN.S147591] [PMID: 29255359]
[74]
Jeganathan, S.; Budziszewski, E.; Hernandez, C.; Dhingra, A.; Exner, A.A. Improving treatment efficacy of in situ forming implants via concurrent delivery of chemotherapeutic and chemosensitizer. Sci. Rep., 2020, 10(1), 6587.
[http://dx.doi.org/10.1038/s41598-020-63636-x] [PMID: 32313056]
[75]
Li, X.; Fan, R.; Wang, Y.; Wu, M.; Tong, A.; Shi, J.; Xiang, M.; Zhou, L.; Guo, G. In situ gel-forming dual drug delivery system for synergistic combination therapy of colorectal peritoneal carcinomatosis. RSC Advances, 2015, 5(123), 101494-101506.
[http://dx.doi.org/10.1039/C5RA21067D]
[76]
Confortini, O. Thermo-responsive graft copolymers based on poly(methyl vinyl ether): From synthesis to evaluation. Group, 2009, 265.
[77]
Bucatariu, S.M.; Constantin, M.; Varganici, C.D.; Rusu, D.; Nicolescu, A.; Prisacaru, I.; Carnuta, M.; Anghelache, M.; Calin, M.; Ascenzi, P.; Fundueanu, G. A new sponge-type hydrogel based on hyaluronic acid and poly(methylvinylether-alt-maleic acid) as a 3D platform for tumor cell growth. Int. J. Biol. Macromol., 2020, 165(Pt B), 2528-2540.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.10.095] [PMID: 33098901]
[78]
Varshosaz, J.; Jahanian-Najafabadi, A.; Ghazzavi, J. Luteinizing hormone-releasing hormone targeted poly(methyl vinyl ether maleic acid) nanoparticles for doxorubicin delivery to MCF-7 breast cancer cells. IET Nanobiotechnol., 2016, 10(4), 206-214.
[http://dx.doi.org/10.1049/iet-nbt.2015.0056] [PMID: 27463791]
[79]
Madhusudana Rao, K.; Mallikarjuna, B.; Krishna Rao, K.S.V.; Siraj, S.; Chowdoji Rao, K.; Subha, M.C.S. Novel thermo/pH sensitive nanogels composed from poly(N-vinylcaprolactam) for controlled release of an anticancer drug. Colloids Surf. B Biointerfaces, 2013, 102, 891-897.
[http://dx.doi.org/10.1016/j.colsurfb.2012.09.009] [PMID: 23107966]
[80]
Mohammed, M.N.; Yusoh, K.B.; Shariffuddin, J.H.B.H. Poly(N-vinyl caprolactam) thermoresponsive polymer in novel drug delivery systems: A review. Mater. Express, 2018, 8(1), 21-34.
[http://dx.doi.org/10.1166/mex.2018.1406]
[81]
Xiao, T.; Hu, W.; Fan, Y.; Shen, M.; Shi, X. Macrophage-mediated tumor homing of hyaluronic acid nanogels loaded with polypyrrole and anticancer drug for targeted combinational photothermo-chemotherapy. Theranostics, 2021, 11(14), 7057-7071.
[http://dx.doi.org/10.7150/thno.60427] [PMID: 34093871]
[82]
Kavitha, T.; Kang, I.K.; Park, S.Y. Poly(N-vinyl caprolactam) grown on nanographene oxide as an effective nanocargo for drug delivery. Colloids Surf. B Biointerfaces, 2014, 115, 37-45.
[http://dx.doi.org/10.1016/j.colsurfb.2013.11.022] [PMID: 24316754]
[83]
Anirudhan, TS; Christa, J Temperature and pH sensitive multi-functional magnetic nanocomposite for the controlled delivery of 5-fluorouracil, an anticancer drug. J Drug Deliv Sci Technol., 2020, 55, 101476.
[http://dx.doi.org/10.1016/j.jddst.2019.101476]
[84]
Xu, F.; Zhu, J.; Lin, L.; Zhang, C.; Sun, W.; Fan, Y.; Yin, F.; van Hest, J.C.M.; Wang, H.; Du, L.; Shi, X. Multifunctional PVCL nanogels with redox-responsiveness enable enhanced MR imaging and ultrasound-promoted tumor chemotherapy. Theranostics, 2020, 10(10), 4349-4358.
[http://dx.doi.org/10.7150/thno.43402] [PMID: 32292499]
[85]
Stawski, D.; Nowak, A. Thermal properties of poly(N,N-dimethylaminoethyl methacrylate). PLoS One, 2019, 14(6), e0217441.
[http://dx.doi.org/10.1371/journal.pone.0217441] [PMID: 31166982]
[86]
Bashir, R.; Maqbool, M.; Ara, I.; Zehravi, M. An In sight into novel drug delivery system : In situ gels. Cell Med., 2021, 11(1), 1-7.
[87]
Wang, X.; Liu, G.; Ma, J.; Guo, S.; Gao, L.; Jia, Y.; Li, X.; Zhang, Q. In situ gel-forming system: An attractive alternative for nasal drug delivery. Crit. Rev. Ther. Drug Carrier Syst., 2013, 30(5), 411-434.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2013007362] [PMID: 24099327]
[88]
Ruel-Gariépy, E.; Shive, M.; Bichara, A.; Berrada, M.; Le Garrec, D.; Chenite, A.; Leroux, J.C. A thermosensitive chitosan-based hydrogel for the local delivery of paclitaxel. Eur. J. Pharm. Biopharm., 2004, 57(1), 53-63.
[http://dx.doi.org/10.1016/S0939-6411(03)00095-X] [PMID: 14729080]
[89]
Kelly, H.; Duffy, G.; Rossi, S. and Hastings, C.; Royal College of Surgeons in Ireland. Thermo-responsive hydrogel for intratumoral administration as a treatment in solid tumor cancers. U.S. Patent Application 17/979,506, 2003.
[90]
Slater, J.H.; Pradhan, S. and Reyes, C.J.F. University of Delaware, 2020. Crosslinked hydrogel compositions for regulating states of encapsulated cancer cells. U.S. Patent Application 16/893,330.
[91]
Immunomodulating treatments of body cavities. patent EP3708167A1, 2020.
[92]
A kind of preparation method and applications based on magnetic oxygenated graphene situ-gel. patent CN104758930B, 2015.
[93]
Hickerson, R.P.; Wey, W.C.; Rimm, D.L.; Speaker, T.; Suh, S.; Flores, M.A. Gene silencing in skin after deposition of self-delivery siRNA with a motorized microneedle array device. Mol Ther Nucleic Acids., 2013, 2(10), e129.
[http://dx.doi.org/10.1038/mtna.2013.56]
[94]
Cheng, F.; Lu, M.J.; Ko, Y.J.; Lin, M.Y. and Shuen-Hsiang, C.H.O.U. Industrial Technology Research Institute ITRI. Recipe for in-situ gel, and implant, drug delivery system formed thereby. U.S. Patent 9,757,330, 2017.
[95]
Choonara, Y.E.; Kondiah, P.P.D.; Kondiah, P.J.; Kumar, P.; Du Toit, L.C.; Marimuthu, T. and Pillay, V. University of the Witwatersrand. Thermoresponsive hydrogel. U.S. Patent 11,197,948, 2021.
[96]
Domb, A.J. and Berlin, J. City of Hope. Programmable thermoresponsive gels. U.S. Patent Application 16/622,656 2020.
[97]
Wadee, A.; Pillay, V.; Choonara, Y.E. and Du Toit, L.C.; University of the Witwatersrand. Implant for the controlled release of pharmaceutically active agents. U.S. Patent Application 13/989,346, 2014.
[98]
Compositions and related methods for targeted drug delivery. patent WO2018106998A1, 2018.
[99]
https://www.freepatentsonline.com/9364545.pdf Jhan, H.J.; Ho, H.O.; Sheu, M.T.; Shen, S.C.; Ho, Y.S. and Jun-Jen, L.I.U. Taipei Medical University TMU. Thermosensitive injectable hydrogel for drug delivery. U.S. Patent 9,364,545, 2016.
[100]
Gong, T.; Song, X.; Zhang, Z.; Zhang, Y.; Guangfei, W.E.I.; Hu, M.; Tijia, C.H.E.N.; Sun, X. and Fu, Y. Sichuan University and YaoPharma Co Ltd. In situ phase change gel sustained-release system for small molecule drug and preparation method thereof. U.S. Patent Application 16/489,353, 2020.
[101]
Ahmed, T.A.; Khalid, M.; Ahmed, O.A. and Aljaeid, B.M. King Abdulaziz University. In situ gelling composition containing tocopherol-loaded micelles as an intranasal drug delivery system. U.S. Patent 10,736,843, 2020.
[102]
Radiopaque Hydrogel in Patients Undergoing Radiotherapy for Pancreatic Cancer. Clinical trial number NCT03307564, 2017.
[103]
TraceIT Tissue Marker to Mark the Primary Resection Bed Margins of Oropharyngeal Cancers. Clinical trial number NCT03713021, 2017.
[104]
Organ-sparing With TraceIT® for Rectal Cancer Radiotherapy. Clinical trial number NCT03258541, 2017.
[105]
Prostate-Rectal Separation With PEG Hydrogel and Its Effect on Decreasing Rectal Dose. Clinical trial number NCT02212548, 2014.
[106]
TracelT hydrogel in localizing bladder tumors in patients undergoing radiation therapy for bladder cancer. Clinical trial number NCT03125226, 2017.

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