THERMOSENSITIVE HYDROGELS–A POTENTIAL CARRIER FOR THE DELIVERY OF DRUGS AND MACROMOLECULES
Keywords:Thermo-sensitive hydrogels, Gelation property, Delivery of drugs, Tissue regeneration
In this review, the authors have discussed scientific advances in thermosensitive hydrogels over the past two decades. The ability of the thermo-sensitive hydrogel to undergo rapid changes with response to temperature makes it an attractive candidate for many biomedical applications such as targeted drug delivery, wound healing, soft contact lenses, sensors, tissue regeneration, gene, and protein delivery. This review aims to deliver a brief overview of gelation properties, merits, and demerits of various natural and synthetic thermo-sensitive polymers that have significant clinical relevance. The report emphasizes the importance of injectable thermosensitive hydrogels, as it can offer improved solubility of hydrophobic drugs and site-specificity, extended-release of drugs and macromolecules, improved safety, and local administration of drugs. The authors has also provided a commentary on the delivery of drugs or macromolecules from thermo-sensitive hydrogels through various approaches. This review highlights the current status of research in thermo-sensitive hydrogels and emphasizes the importance of developing nontoxic thermo-sensitive hydrogels, dual responsive, and multi-responsive hydrogel systems.
Xing JF, Zheng ML, Duan XM. Two-photon polymerization microfabrication of hydrogels: an advanced 3D printing technology for tissue engineering and drug delivery. Chem Soc Rev 2015;44:5031–9.
Macaya D, Spector M. Injectable hydrogel material for spinal cord regeneration: a review. Biomed Mater 2012;7:012001.
Surojeet D, Vivek K, Rini T, Leena S, Sachidanand S. Recent advances in hydrogels for biomedical applications. Asian J Pharm Clin Res 2018;11:62-8.
Sabbagh F, Kiarostami K, Khatir NM, Rezania S, Muhamad I. Green synthesis of Mg0.99 Zn0.01O nanoparticles for the fabrication of κ-carrageenan/NaCMC hydrogel to deliver catechin. Polym 2020;12:861.
Hu W, Wang Z, Xiao Y, Zhanga S, Wang J. Advances in crosslinking strategies of biomedical hydrogels. Biomater Sci 2019;7:843-55.
Sabbagh F, Khatir NM, Karim AK, Omidvar A, Nazari Z, Jaberi R. Mechanical properties and swelling behavior of acrylamide hydrogels using montmorillonite and kaolinite as clays. J Environ Treat Tech 2011;7:211-9.
Huh HW, Zhao L, Kim SY. Biomineralized biomimetic organic/inorganic hybrid hydrogels on hyaluronic acid and poloxamer. Carbohydr Polym 2015;1:130-40.
Garima S, Alka L, Shiv Sankar B. Hydrogel as a novel drug delivery system: a review. J Fundam Pharm Res 2014;2:35-48.
Tibbitt MW, Anseth KS. Hydrogels as extracellular matrix mimic for 3D cell culture. Biotechnol Bioeng 2009;103:655–63.
Jamstorp Berg E. Diffusion controlled drug release from slurry formed, porous, organic, and clay-derived pellets (Doctoral dissertation. Acta Universitatis Upsaliensis; 2012. p. 80.
Nesrinne S, Djamel A. Synthesis, characterization, and rheological behavior of pH-sensitive poly (acrylamide-co-acrylic acid) hydrogels. Arabian J Chem 2017;10:539-47.
Anita D, Ujjwal N, Sarabjot K, Komal. Hydrogels: a smart drug delivery device. Asian Pac J Health Sci 2014;1:92-105.
Matanovic MR, Kristl J, Grabnar PA. Thermoresponsive polymers: Insights into decisive hydrogel characteristics, mechanisms of gelation, and promising biomedical applications. Int J Pharm 2014;472:262–75.
Ishida K, Uno T, Itoh T, Kubo M. Synthesis and property of temperature-responsive hydrogel with movable cross-linking points. Macromolecules 2012;45:6136–42.
Liu YY, Shao YH, Jian L. Preparation, properties and controlled release behaviors of pH-induced thermosensitive amphiphilic gels. Biomaterials 2006;27:4016–24.
Qiu Y, Park K. Environment-sensitive hydrogels for drug delivery. Adv Drug Delivery Rev 2001;53:321–39.
Elena B, Andrea LS, Steven RL, Paolo D. Injectable thermoresponsive hydrogels as a drug delivery system for the treatment of central nervous system disorders: a review. J Controlled Release 2021;329:19-9.
Gariepy ER, Leroux JC. In situ-forming hydrogels-review of temperature-sensitive systems. Eur J Pharm Biopharm 2004;58:409-26.
Fundueanu G, Constantin M, Asmarandei I, Bucatariu S, Harabagiu V, Scenzi P, et al. Poly (N-isopropyl acrylamide-co-hydroxy ethyl acrylamide) thermosensitive microspheres: the size of microgels dictates the pulsatile release mechanism. Eur J Pharm Biopharm 2013;85:614–23.
Lee JW, Jung MC, Park HD, Park KD, Ryu GH. Synthesis and characterization of thermosensitive chitosan copolymer as a novel biomaterial. J Biomater Sci Polym Ed 2004;15:1065–79.
Ward MA, Georgiou TK. Thermoresponsive terpolymers based on methacrylate monomers: effect of architecture and composition. J Polym Sci Part A: Polym Chem 2010;48:775–83.
Li Z, Wang F, Roy S, Sen CK, Guan J. Injectable, highly flexible, and thermosensitive hydrogels capable of delivering superoxide dismutase. Biomacromolecules 2009;10:3306–16.
Chitra G, Vijay J, Upendra N. Formulation and optimization of thermosensitive in-situ gel of moxifloxacin hydrochloride for ocular drug delivery. Int J Appl Pharm 2018;3:123-30.
Gong C, Qi T, Wei X, Qu Y, Wu Q, Luo F, et al. Thermosensitive polymeric hydrogels as drug delivery systems. Curr Med Chem 2013;20:79–94.
Li SK, Emanuele AD. On-off transport through a thermoresponsive hydrogel composite membrane. J Controlled Release 2001;75:55–67.
Schild HG, Tirrell DA. Micro calorimetric detection of lower critical solution temperatures in aqueous polymer solutions. J Phys Chem 1990;94:4352–6.
Huang H, Qi X, Chen Y, Wu Z. Thermo-sensitive hydrogels for delivering biotherapeutic molecules: a review. Saudi Pharm J 2019;27:990-9.
Sudipta C, Patrick CH, Kan C. Thermoresponsive hydrogels and their biomedical applications: special insight into their applications in textile based transdermal therapy. MDPI 2018;10:480.
Pillai O, Panchagnula R. Polymers in drug delivery. Curr Opin Chem Biol 2001;5:447-51.
Li L, Shan H, Yue CY, Lam YC, Tam KC, Hu X. Thermally induced association and dissociation of methylcellulose in aqueous solutions. Langmuir 2002;18:7291–8.
Takahashi M, Shimazaki M, Yamamoto J. Thermoreversible gelation, and phase separation in aqueous methylcellulose solutions. J Polym Sci Part B: Polym Phys 2001;39:91–100.
Liu W, Zhang B, Lu WW, Li X, Zhu D, De Yao K, et al. A rapid temperature-responsive sol-gel reversible poly (N-isopropyl acrylamide)-g-methylcellulose copolymer hydrogel. Biomaterials 2004;25:3005-12.
Maite AP, Leyre PA, Luis Carlos CI, Issa K. Biodegradable chitosan nano gels crosslinked with genipin. Carbohydr Polym 2013;94:836–42.
Xiao C, You R, Fan Y, Zhang Y. Tunable functional hydrogels formed from versatile water-soluble chitosan. Int J Biol Macromol 2016;85:386–90.
Hamidi M, Azadi A, Rafiei P. Hydrogel nanoparticles in drug delivery. Adv Drug Delivery Rev 2008;60:1638-49.
Esquerdo V, Cadaval T, Dotto G, Pinto L. Chitosan scaffold as an alternative adsorbent for the removal of hazardous food dyes from aqueous solutions. J Colloid Interface Sci 2014;424:7-15.
Chenite A, Chaput C, Wang D, Combes C, Buschmann MD, Hoemann CD, et al. Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials 2000;21:2155–61.
Qi FD, Jing QY, Hong L, Cheng SL, Xi GC, Qiu XJ, et al. Biological evaluation of chitosan-based in-situ forming hydrogel with a low phase transition temperature. J Appl Polym Sci 2015;132:41594.
Anuja N, Hema N. Formulation and evaluation of thermosensitive bio gels for the nose to brain delivery of doxepin. Biomed Res Int 2014. https://doi.org/10.1155/2014/847547
Supper S, Anton N, Seidel N, Riemenschnitter M, Schoch C, Vandamme T. Rheological study of chitosan/polyol-phosphate systems: influence of the polyol part on the thermo-induced gelation mechanism. Langmuir 2013;29:10229–37.
Bhattarai N, Matsen FA, Zhang M. PEG-grafted chitosan as an injectable thermoreversible hydrogel. Macromol Biosci 2005;5:107–11.
Nazara H, Fatouros DG, Van der Merwe SM, Bouropoulos G, Avgouropoulos G, Tsibouklis J, et al. Thermosensitive hydrogels for nasal drug delivery: The formulation and characterization of systems based on N-trimethyl chitosan chloride. Eur J Pharm Biopharm 2011;77:225-32.
Semenzato A, Costantini A, Baratto G. Green polymers in personal care products: rheological properties of tamarind seed polysaccharide. Cosmetics 2015;2:1–10.
Martinez Ibarra DM, Lopez Cervantes J, Sanchez Machado DI, Sanches Silva A. Chitosan and xyloglucan-based hydrogels: an overview of synthetic and functional utility. chitin-chitosan-myriad functionalities in science and technology. Intech Open 2018;184-18:74646.
Pique N, Carmen Gomez Guillen MD, Montero MP. Xyloglucan, a plant polymer with barrier protective properties over the mucous membranes: an overview. Int J Mol Sci 2018;19:673.
Picone P, Sabatino MA, Ajovalasit A, Giacomazza D, Dispenza C, Di Carlo M. Biocompatibility, hemocompatibility and antimicrobial properties of xyloglucan based hydrogel film for wound healing application. Int J Biol Macromol 2019;121:784–95.
Zhang E, Li L, Zhou Y, Che P, Ren B, Qin Z, et al. Biodegradable and injectable thermoreversible xyloglucan-based hydrogel for prevention of postoperative adhesion. Acta Biomater 2017;55:420–33.
Amanda K, Brun Graeppi AS, Richard C, Bessodes M, Scherman D, Narita T, et al. Study on the sol-gel transition of xyloglucan hydrogels. Carbohydr Polym 2010;80:555–63.
Moneo Sanchez M, Alonso Chico A, Knox JP, Dopico B, Labrador E, Martin I. β-(1, 4)-galactan remodeling in arabidopsis cell walls affects the xyloglucan structure during elongation. Planta 2018;249:351–62.
Chen D, Guo P, Chen S, Cao Y, Ji W, Lei X, et al. Properties of xyloglucan hydrogel as the biomedical sustained-release carriers. J Mater Sci Mater Med 2012;23:955–62.
Ajovalasit A, Sabatino MA, Todaro S, Alessi S, Giacomazza D, Picone P, et al. Xyloglucan-based hydrogel films for wound dressing: structure-property relationships. Carbohydr Polym 2017;179:262–72.
Mahajan HS, Tyagi V, Lohiya G, Nerkar P. Thermally reversible xyloglucan gels as vehicles for nasal drug delivery. Drug Delivery 2012;19:270–6.
Kulkarni AD, Joshi AA, Patil CL, Amale PD, Patel HM, Surana SJ, et al. Xyloglucan: a functional biomacromolecule for drug delivery applications. Int J Biol Macromol 2017;104:799–12.
Simi CK, Abraham TE. Transparent xyloglucan–chitosan complex hydrogels for different applications. Food Hydrocoll 2010;24:72–80.
Nisbet DR, Rodda AE, Horne MK, Forsythe JS, Finkelstein DI. Implantation of functionalized thermally gelling xyloglucan hydrogel within the brain: associated neurite infiltration and inflammatory response. Tissue Eng Part A 2010;16:2833–42.
Ye L, Wu X, Mu Q, Chen B, Duan YH, Geng X, et al. Heparin-conjugated PCL scaffolds fabricated by electrospinning and loaded with fibroblast growth factor 2. J Biomater Sci Polym Ed 2011;22:389–406.
Silva AK, Richard C, Ducouret G, Bessodes M, Scherman D, Merten OW. Xyloglucan-derivatized films for the culture of adherent cells and their Thermo controlled detachment: a promising alternative to cells sensitive to protease treatment. Biomacromolecules 2013;14:512-9.
Prabaharan M, Mano JF. Stimuli-responsive hydrogels based on polysaccharides incorporated with thermo-responsive polymers as novel biomaterials. Macromol Biosci 2006;6:991-1008.
Kim MS, Park SJ, Chun HJ, Kim CH. Thermosensitive hydrogels for tissue engineering. Tissue Eng Regener Med 2011;8:117-23.
Young S, Wong M, Tabata Y, Mikos AG. Gelatin as a delivery vehicle for the controlled release of bioactive molecules. J Controlled Release 2005;109:256–74.
Joly Duhamel C, Hellio D, Djabourov M. All gelatin networks: 1. Biodiversity and physical chemistry. Langmuir 2002;18:7208–17.
Das N. Bio-degradable hydrogels for controlled drug delivery. Cellulose Based Super Absorbent Hydrogels 2019;48:1434-70.
Yang H, Kao WJ. Thermoresponsive gelatin/mono methoxy poly (ethylene glycol)-poly (d, l-lactide) hydrogels: formulation, characterization, and antibacterial drug delivery. Pharm Res 2006;23:205-14.
Alexander A, Ajazuddin, Khan J, Saraf S, Saraf S. Poly (ethylene glycol)–poly (lactic-co-glycolic acid) based thermosensitive injectable hydrogels for biomedical applications. J Controlled Release 2013;172:715–29.
Leda K. Thermoresponsive hydrogels in biomedical applications: a seven-year update. Eur J Pharm Biopharm 2015;97:338–49.
Wang Q, Zuo Z, Chucky Cheung CK, Yee Leung SS. Updates on thermosensitive hydrogel for nasal, ocular and cutaneous delivery. Int J Pharm 2019;559:86–101.
Le PN, Huynh CK, Tran NQ. Advances in thermosensitive polymer-grafted platforms for biomedical applications. Mater Sci Eng C Mater Biol Appl 2018;92:1016-30.
Darge HF, Andrgie AT, Tsai HC, Lai JY. Polysaccharide and polypeptide based injectable thermosensitive hydrogels for local biomedical applications. Int J Biol Macromol 2019;133:545–63.
Yin X, Hoffman AS, Stayton PS. Poly (N-isopropyl acrylamide-co-propyl acrylic acid) copolymers that respond sharply to temperature and pH. Biomacromolecules 2006;7:1381–5.
Masamichi N, Teruo O, Takanari M, Fukashi K, Kiyotaka S, Masayuki Y. Molecular design of biodegradable polymeric micelles for temperature-responsive drug release. J Controlled Release 2006;115:46–56.
Coughlan DC, Quilty FP, Corrigan OI. Effect of drug physicochemical properties on swelling/deswelling kinetics and pulsatile drug release from thermoresponsive poly(N–isopropyl acrylamide) hydrogels. J Controlled Release 2004;98:97–114.
Pei Y, Chen J, Yang L, Shi L, Tao Q, Hui B, et al. The effect of pH on the LCST of poly (N-isopropyl acrylamide) and poly(N-isopropyl acrylamide-co-acrylic acid). J Biomater Sci Polym Ed 2004;15:585–94.
Kim YJ, Kim SW. Controlled drug delivery from the injectable biodegradable triblock copolymer. ACS Sympos 2002;833:300–11.
Tirtaatmadja N, Murphy KT, Lynch GS, Connor OA. Mixed micelles to deliver drugs for skeletal muscle regeneration. In: Proceedings of the international society, Asia Paciﬁc Meeting, Sydney, Australia, September; 2010.
Gulsen D, Chauhan A. Dispersion of microemulsion drops in HEMA hydrogel: a potential ophthalmic drug delivery vehicle. Int J Pharm 2005;292:95–117.
Kim J, Conway A, Chauhan A. Extended delivery of ophthalmic drugs by silicone hydrogel contact lenses. Biomaterials 2008;29:2259–69.
Lin Z, Gao W, Hu H, Ma K, He B, Dai W, et al. Novel thermo-sensitive hydrogel system with paclitaxel nanocrystals: high drug-loading, sustained drug release and extended local retention guaranteeing better efﬁcacy and lower toxicity. J Controlled Release 2014;174:161–70.
Jeong B, Kim SW, Bae YH. Thermosensitive sol-gel reversible hydrogels. Adv Drug Delivery Rev 2002;54:37-51.
Madan M, Bajaj A, Lewis S, Udupa N, Baig J. In situ forming polymeric drug delivery systems. Indian J Pharm Sci 2009;71:242-51.
Lin Z, Mei D, Chen M, Wang Y, Chen X, Wang Z, et al. A comparative study of thermo-sensitive hydrogels with water-insoluble paclitaxel in the molecule, nanocrystal, and microcrystal dispersions. Nanoscale 2015;7:14838–47.
Gong CY, Shi S, Dong PW, Zheng XL, Fu SZ, Guo G, et al. In vitro drug release behavior from a novel thermosensitive composite hydrogel based on pluronic f127 and poly (ethylene glycol)-poly (ε-caprolactone)-poly (ethylene glycol) copolymer. BMC Biotechnol 2009;9:8.
Cohn D, Sosnik A, Malal R, Zarka R, Garty S, Levy A. Chain extension as a strategy for the development of improved reverse thermo-responsive polymers. Polym Adv Technol 2007;18:731–6.
Yang Z, Nie S, Hsiao WW, Pam W. Thermo reversible Pluronic® F127-based hydrogel containing liposomes for the controlled delivery of paclitaxel: In vitro drug release, cell cytotoxicity, and uptake studies. Int J Nanomed 2011;6:151-66.
Yang Y, Wang J, Zhang X, Lu W, Zhang Q. A novel mixed micelle gel with thermo-sensitive property for the local delivery of docetaxel. J Controlled Release 2009;135:175–82.
Cheng Y, He C, Ding J, Xiao C, Zhuang X, Chen X. Thermo-sensitive hydrogels based on polypeptides for localized and sustained delivery of anticancer drugs. Biomaterials 2013;34:10338–47.
Bindu Sri M, Ashok V, Chatterjee A. A review on hydrogels as drug delivery in the pharmaceutical field article. Int J Pharm Chem Sci 2012;1:642-61.
Ali S, Yosipovitch G, Skin PH. From basic science to basic skin care. Acta Derm Venereol 2013;93:261–7.
Gong C, Wu Q, Wang Y, Zhang D, Luo F, Zhao X, et al. A biodegradable hydrogel system containing curcumin encapsulated in micelles for cutaneous wound healing. Biomaterials 2013;34:6377–87.
Chen X, Peng LH, Shan YH, Li N, Wei W, Yu L, et al. Astragaloside IV-loaded nanoparticle-enriched hydrogel induces wound healing and anti-scar activity through topical delivery. Int J Pharm 2013;447:171–81.
Xi L, Wang T, Zhao F, Zheng Q, Li X, Luo J, et al. Evaluation of an Injectable thermosensitive hydrogel as drug delivery implant for ocular glaucoma surgery. PLoS One 2014;9:e100632.
Ryu JM, Chung SJ, Lee MH, Kim CK, Shim CK. Increased bioavailability of propranolol in rats by retaining thermally gelling liquid suppositories in the rectum. J Controlled Release 1999;59:163-72.
Miyazaki S, Suisha F, Kawasaki N, Shirakawa M, Yamatoya K, Attwood D. Thermally reversible xyloglucan gels as vehicles for rectal drug delivery. J Controlled Release 1998;56:75-83.
Goswami T, Jasti B, Li X. Sublingual drug delivery. Crit Rev Ther Drug Carrier Syst 2008;25:449–84.
Wang Z, Chow MS. Overview and appraisal of the current concept and technologies for improvement of sublingual drug delivery. Ther Delivery 2014;5:807–16.
Ferreira L, Gil MH, Dordick JS. Enzymatic synthesis of dextran-containing hydrogels. Biomaterials 2002;23:3957-67.
Salgado Rodriguez R, Licea Claverie A, Arndt KF. Random copolymers of N Isopropyl acrylamide and methacrylic acid monomers with hydrophobic spacers: pH tunable temperature-sensitive materials. Eur Polym J 2004;40:1931-46.
Almeida JF, Ferreira P, Alves P, Lopes A, Gil MH. Thermal-responsive hydrogels for sublingual administration of Ondansetron™. Int J Polymeric Materials Polymeric Biomaterials 2017;67:765-75.
Chinna Reddy P, Chaitanya KSC, Madhusudan Rao Y. A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods. Daru 2011;19:385–403.
Zenga N, Dumortier G, Maury M, Mignet N, Boudya V. Influence of additives on a thermosensitive hydrogel for buccal delivery of salbutamol: relation between micellization, gelation, mechanic and release properties. Int J Pharm 2014;467:70-83.
Sandri G, Bonferroni MC, Ferrari F, Rossi S, Del Fante C, Perotti C, et al. An in situ gelling buccal spray containing platelet lysate for the treatment of oral mucositis. Curr Drug Discovery Technol 2011;8:277–85.
Park JS, Oh YK, Yoon H, Kim JM, Kim CK. In situ gelling and mucoadhesive polymer vehicles for controlled intranasal delivery of plasmid DNA. J Biomed Mater Res 2002;59:144-51.
Choi SG, Lee SE, Kang BS, Ng CL, Davaa E. Thermosensitive and mucoadhesive sol-gel composites of paclitaxel/dimethyl-b-cyclodextrin for buccal delivery. PLoS One 2014;9:e109090.
Vermonden T, Fedorovich NE, Geemen DV, Alblas J, van Nostrum CF. Photo-polymerized thermosensitive hydrogels: synthesis, degradation, and cytocompatibility. Biomacromolecules 2008;9:919–26.
Kabanov AV. Polymer genomics: an insight into pharmacology and toxicology of nanomedicines. Adv Drug Delivery Rev 2006;58:1597-621.
Turabee MH, Jeong TH, Ramalingam P, Kang JH, Ko YT. N, N, N-trimethyl chitosan embedded in situ pluronic F127 hydrogels for the treatment of brain tumor. Carbohydr Polym 2019;203:302–9.
Cho JK, Hong KY, Park JW, Yang HK, Song SC. The injectable delivery system of 2-methoxy estradiol for breast cancer therapy using biodegradable thermosensitive poly (organophosphazene) hydrogel. J Drug Target 2011;19:270-80.
Han HD, Song CK, Park YS, Noh KH, Kim JH, Hwang T, et al. A chitosan hydrogel-based cancer drug delivery system exhibits synergistic antitumor effects by combining with a vaccinia viral vaccine. Int J Pharm 2008;350:27–34.
Kwon JS, Park IK, Cho AS, Shin SM, Hong MH, Jeong SY, et al. Enhanced angiogenesis mediated by vascular endothelial growth factor plasmid-loaded thermo-responsive amphiphilic polymer in a rat myocardial infarction model. J Controlled Release 2009;138:168-76.
Oh KS, Song JY, Yoon SJ, Park Y, Kim D, Yuk SH. Temperature-induced gel formation of core/shell nanoparticles for the regeneration of the ischemic heart. J Controlled Release 2010;146:207-11.
Xu HL, Xu J, Zhang SS, Zhu QY, Jin BH, Zhuge DL, et al. Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus. Drug Delivery 2017;24:867–81.
Chen D, Zhang C, Huo H, Ji C, Sun M, Nie L. Injectable temperature-sensitive hydrogel with VEGF loaded microspheres for vascularization and bone regeneration of femoral head necrosis. Mater Lett 2018;229:138–41.
Wong YC, Zuo Z. Brain disposition and catalepsy after intranasal delivery of loxapine: role of metabolism in PK/PD of intranasal CNS drugs. Pharm Res 2013;30:2368–84.
Deshpande ST, Lahoti SR, Dhamecha DL, Rajendra VB, Dehghan MHG, Puranik PK. Enhanced iontophoretic delivery of sumatriptan succinate from the thermosensitive gel using chemical enhancers. Indian J Pharm Ed Res 2013;47:27–33.
Shirui Pu, Jiaxuan Su, Liuxiang Li, Wang Hs, Chen C, Xuejiao Hu. Bioinspired sweating with temperature-sensitive hydrogel to passively dissipate heat from high-end wearable electronics. Energy Conversion Management 2019;180:747-56.
Mura P, Mennini N, Nativi C, Richichi B. In situ mucoadhesive-thermosensitive liposomal gel as a novel vehicle for nasal extended delivery of opiorphin. Eur J Pharm Biopharm 2018;122:54-61.
Shuangxia R, Yu D, Cuiyun L, Qiu Z, Wang X, Tian F, et al. Pharmacokinetics and pharmacodynamics evaluation of a thermosensitive chitosan-based hydrogel containing liposomal doxorubicin. Eur J Pharm Sci 2016;92:137-45.
Cheng YH, Ko YC, Chang YF, Huang SH, Liu CJ. The thermosensitive chitosan-gelatin-based hydrogel containing curcumin-loaded nanoparticles and latanoprost as a dual-drug delivery system for glaucoma treatment. Exp Eye Res 2019;179:179-87.
Xu G, Zhu C, Li B, Wang T, Wan J, Zhang Y. improving the anti-ovarian cancer activity of docetaxel by self-assemble micelles and thermosensitive hydrogel drug delivery system. J Biomed Nanotechnol 2020;16:40-53.
Tavakoli N, Taymouri S, Saeidi A, Akbari V. Thermosensitive hydrogel containing sertaconazole loaded nanostructured lipid carriers for the potential treatment of fungal keratitis. Pharm Dev Technol 2019;24:891-901.
Saeednia L, Yao L, Cluff K, Asmatulu R. sustained releasing of methotrexate from injectable and thermosensitive chitosan-carbon nanotube hybrid hydrogels effectively controls tumor cell growth. ACS Omega 2019;4:4040-8.
Shelke S, Shahi S, Jalalpure S, Dhamecha D. Poloxamer 407-based intranasal thermoreversible gel of zolmitriptan-loaded nanoethosomes: formulation, optimization, evaluation, and permeation studies. J Liposome Res 2016;26:313–23.
Sheu MT, Jhan HJ, Su CY, Chen LC, Chang CE, Liu DZ, et al. Codelivery of doxorubicin containing thermosensitive hydrogels incorporated with docetaxel-loaded mixed micelles enhance local cancer therapy. Colloids Surfaces B 2016;143:260-70.
Marwah H, Garg T, Rath G, Goyal AK. Development of transferosomal gel for transdermal delivery of insulin using iodine complex. Drug Delivery 2016;23:1636–44.
Jose S, Ansa CR, Cinu TA, Chacko AJ, Aleykutty NA, Ferreira SV, et al. Thermo-sensitive gels containing lorazepam microspheres for intranasal brain targeting. Int J Pharm 2013;441:516–26.
Xu S, Fan H, Yin L, Zhang J, Dong A, Deng LD, et al. Thermosensitive hydrogel system assembled by PTX-loaded copolymer nanoparticles for sustained intraperitoneal chemotherapy of peritoneal carcinomatosis. Eur J Pharm Biopharm 2016;104:251–9.
Zhang X, Sun GH, Tian MP, Wang YN, Qu CC, Cheng XJ, et al. Mussel-inspired antibacterial polydopamine/chitosan/temperature-responsive hydrogels for rapid hemostasis. Int J Biol Macromol 2019;138:321-33.