当前位置:
首页
网刊
温度敏感型水凝胶载药系统的最新研究与应用
温度敏感型水凝胶载药系统的最新研究与应用
齐学洁1,2,刘香云1,2,邱 峰1,2

天津中医药大学中药学院,天津 300193;2 天津市中药药理学重点实验室,天津 300193
Latest research and application on the thermo-sensitive  hydrogels drug delivery systems
(1 Chinsese Medicine School of TCM, Tianjin University of TCM, Tianjin 300193, China;  2 Tianjin State Key Laboratory of Pharmacology Chinese Medicine, Tianjin 300193, China)

摘要参考文献相关文章

起始页:2533

摘要:[摘要] 温度敏感型水凝胶系统因为能够根据环境温度的变化而发生溶胶-凝胶的相转变,以溶液状态给药,在给药部位迅速形成药物储库,具有缓释、控释、靶向给药等优势而倍受研究者关注。本文从温度敏感型水凝胶的制备、组成分类、凝胶化机制和生物医药学应用等方面进行综述,为智能型载药系统的临床应用提供理论依据。

关键词:[关键词] 温度敏感;相转变;载药系统;控制释放

通讯作者:

基金项目:

作者简介:

Abstract:[Abstract] Thermo-sensitive hydrogels had gained increasing attention from researchers since the sol-gel phase transition can occur according to the environmental temperature change, and also the solution state administration, the administration site in the rapid formation of a drug reservoir, with controlled release, targeted drug delivery and other advantages. The objective of this review is to summarize the applications and recent advances of thermo-sensitive hydrogels, including preparation, classification, gelation mechanisms and biomedical applications therefore provide theoretical basis for the clinical application of the intelligent drug delivery systems.

Key words:[Key words] thermo-sensitive;phase transition;drug delivery systems;controlled release

    [1] GONG C,QI T,WEI X,et al. Thermosensitive polymeric hydrogels as drug delivery systems

    [J]. Curr Med Chem, 2013, 20(1):79-94.


    [2] HOARE T, KOHANE D. Hydrogels in drug delivery: progress and challenges

    [J]. Polymer, 2008, 49(8):1993-2007.


    [3] QIU Y, PARK K. Environment-sensitive hydrogels for drug delivery

    [J]. Adv Drug Deliv Rev, 2012, 64(3):49-60.


    [4] JEONG B, KIM SW, BAE YH. Thermosensitive sol-gel reversible hydrogels

    [J]. Adv Drug Deliv Rev, 2002, 17, 54(1):37-51.


    [5] LEI N, GONG C, QIAN Z, et al. Therapeutic application of injectable thermosensitive hydrogel in preventing local breast cancer recurrence and improving incision wound healing in a mouse model

    [J]. Nanoscale, 2012, 21,4(18):5686-5693.


    [6] ZHANG D, SUN P, LI P, et al. magnetic chitosan hydrogel for sustained and prolonged delivery of Bacillus Calmettee-Guérin in the treatment of bladder cancer

    [J]. Biomaterials, 2013, 34(38):10258-10266.


    [7] GIRI TK, THAKUR A, ALEXANDER A, et al. Modified chitosan hydrogels as drug delivery and tissue engineering systems: present status and applications

    [J]. Acta Pharm Sin B, 2012, 2(5):439-449.


    [8] JIANG Y, CHEN J, DENG C, et al.Click hydrogels, microgels and nanogels: emerging platforms for drugdelivery and tissue engineering

    [J]. Biomaterials, 2014, 35(18):4969-4985.


    [9] 杜广增,赵浩如. Poloxamer407温敏性即型凝胶的制备和应用进展

    [J]. 药学进展, 2008, 32(4):163-167.


    [10] CHENITE A, CHAPUT C, WANG D, et al. A novel injectable neutral solution of chitosan form biodegradable gels in situ

    [J]. Biomaterials, 2000, 21(21):2155-2161.


    [11] KOJARUNCHITT T, BALDURSDOTTIR S, DONG YD, et al. Modified thermoresponsive Poloxamer407 and chitosan sol-gels as potential sustained-release vaccine delivery systems

    [J]. Eur J Pharm Biopharm, 2015, 89:74-81.


    [12] 吴婷,文秀芳,皮丕辉,等. 互穿网络聚合物的研究进展及应用

    [J]. 材料导报, 2009, 23(5):53-56.


    [13] 李钒. 温度敏感药物释放体系的研究进展

    [J].天津化工, 2016, 30(2):3-5.


    [14] 王于杰,蒋国强,孙佳丽,等. 温敏凝胶原位植入给药系统的研究进展

    [J].精细化工, 2013,30(1):1-6.


    [15] 袁丛辉,余娜,林松柏,等. PVA-PAMPS-PAA 三元互穿网络型水凝胶的合成及其性能研究

    [J]. 高分子学报, 2009(3):249-256.


    [16] 黄首伟,王秀芬,庄慧. (NIPAAm)类三元共聚及IPN水凝胶的合成与温敏性能的研究

    [J].北京化工大学学报, 2009, 36(S1):59-63.


    [17] 张鸿鑫,鲁路,李立华,等. 海藻酸动态共价交联水凝胶的制备及其自愈合性能

    [J]. 高分子学报, 2016,3(3):368-374.


    [18] 冯志云,吴敏,朱昌平,等. 聚乙二醇共价交联海藻酸钠凝胶制备及其药物缓释性能

    [J]. 材料科学与工程学报, 2015, 33(3):368-371,424.


    [19] ROKHADE AP, SHELKE NB, PATIL SA, et al. Novel hydrogel microspheres of chitosan and pluronic F-127 for controlled release of 5-fluorouracil

    [J]. J Microencapsul, 2007, 24(3):274-288.


    [20] SILVA SS, MOTTA A, RODRIGUES MT, et al. Novel genipin-crosslinked chitosan/silk fibroin sponge for cartilage engineering strategies

    [J]. Biomacromolecules, 2008,9(10):2764-2774.


    [21] YOU J, HU FQ, DU YZ, et al. Polymeric micelles with glycolipid-like structure and multiple hydrophobic domain for mediating molecular target delivery of paclitaxel

    [J]. Biomacromolecules, 2007, 8(8):2450-2456.


    [22] PARK KM, LEE SY, JOUNG YK, et al. Thermosensitive chitosan-pluronic hydrogel as an injectable cell delivery carrier for cartilage regeneration

    [J]. Acta Biomate, 2009, 5(6):1956-1965.


    [23] BHATTARAI N, RAMAY HR, GUNN J, et al. PEG-grafted chitosan as an injectable thermosensitive hydrogel for sustained protein release

    [J]. J Control Release, 2005, 103(3): 609-624.


    [24] LEE SY, PEREIRA BP, YUSOF N, et al. Unconfined compression properties of porous poly(vinyl alcohol)-chitosan-based hydrogel after hydration

    [J]. Acta Biomate, 2009, 5(6):1919-1925.


    [25] SUNG JH, HWANG MR, KIM JO, et al. Gel characterisation and in vivo evaluation of minocycline-loaded wound dressing with enhanced wound healing using polyvinyl alcohol and chitosan

    [J]. Int J Pharm, 2010, 392(1-2):232-240.


    [26] ZHOU Y, ZHAO Y, WANG L, et al. Radiation synthesis and characterization of nanosilver/gelatin/carboxymethyl chitosan hydrogel

    [J]. Radiat Phys Chem, 2012, 81(5): 553-560.


    [27] ZHOU HY, JIANG LJ, CAO PP, et al. Glycerophosphate-based chitosan thermosensitive hydrogels and their biomedical applications

    [J]. Carbohydr Polym, 2015, 117:524-536.


    [28] KIM S, NISHIMOTO SK, BUMGARDNER JD, et al. A chitosan/beta-glycerophosphate thermo-sensitive gel for the delivery of ellagic acid for the treatment of brain cancer

    [J]. Biomaterials,2010, 31(14):4157-4166.


    [29] CHEN C, WANG L, DENG L, et al. Performance optimization of injectable chitosan hydrogel by combining physical and chemical triple crosslinking structure

    [J]. J Biomed Mater Res A, 2013, 101(3):684-693.


    [30] LIU X, CHEN Y, HUANG Q, et al. A novel thermo-sensitive hydrogel based on thiolated chitosan/hydroxyapatite/beta-glycerophosphate

    [J]. Carbohydr Polym, 2014, 110(110):62-69.


    [31] DANG QF, YAN JQ, LIN H, et al. Designand evaluation of a highly porous thermosensitive hydrogel with low gelation temperature as a 3D culture system for Penaeus chinensis lymphoid cells

    [J]. Carbohydr Polym, 2012, 88(1):361-368.


    [32] WU Y, WEI W, ZHOU M, et al. Thermal-sensitive hydrogel as adjuvant-free vaccine delivery system for H5N1 intranasal immunization

    [J]. Biomaterials, 2012, 33(7):2351-2360.


    [33] CHEN X, LI X, ZHOU Y, et al. Chitosan-based thermosensitive hydrogel as a promising ocular drug delivery system: Preparation,characterization, and in vivo evaluation

    [J]. J Biomater Appl, 2012, 27(4):391-402.


    [34] YIN X, HOFFMAN A, STAYTON P. Poly (N-isopropylacrylamide-co-propylacrylic acid) copolymers that respond sharply to temperature and pH

    [J]. Biomacromolecules, 2006, 7(5):1381-1385.


    [35] NAKAYAMA M, OKANO T, MIYAZAKI T, et al. Molecular design of biodegradable polymeric micelles for temperature responsive drug release

    [J]. J Control Release, 2006, 115(1):46-56.


    [36] NA K, PARK J, KIM S, et al. Delivery of dexamethasone, ascorbate, and growth factor (TGF

    [beta]-3) in thermo-reversible hydrogel constructs embedded with rabbit chondrocytes

    [J]. Biomaterials, 2006, 27(35):5951-5957.


    [37] SHIMIZU T, YAMATO M, KIKUCHI A, et al. Two-dimensional manipulation of cardiac myocyte sheets utilizing temperature-responsive culture dishes augments the pulsatile amplitude

    [J]. Tissue Eng, 2001, 7(2):141-151.


    [38] TURTURRO SB, GUTHRIE MJ, APPEL AA, et al. The effects of cross-linked thermo-responsive PNIPAAm-based hydrogel injection on retinal function

    [J]. Biomaterals, 2011, 32(14):3620-3626.


    [39] LI C, TANG Y, ARMES SP, et al. Synthesis and characterization of biocompatible thermo-responsive gelators based on ABA triblock copolymers

    [J]. Biomacromolecules, 2005, 6(2):994-999.


    [40] FUJIMOTO KL, MA Z, NELSON DM, et al. Synthesis, characterization and therapeutic efficacy of a biodegradable, thermo-responsive hydrogel designed for application in chronic infracted myocardium

    [J]. Biomaterials, 2009, 30(26):4357-4368.


    [41] WANG F, LI Z, KHAN M, et al. Injiectable, rapid gelling and highly flexible hydrogel composites as growth factor and cell carriers

    [J]. Acta Biomater, 2010, 6(6):1978-1991.


    [42] KIM MR, PARK TG. Temperature responsive and degradable hyaluronic acid /Pluronic composite hydrogels for controlled release of human growth hormone

    [J]. J Control Release, 2002,80(1-3):69-77.


    [43] CHEN PC, KOHANE DS, PARK YJ, et al. Injectable microparticle-gel system for prolonged and localized lidocaine release. II. In vivo anesthetic effects

    [J]. J Biomed Mater Res A, 2004, 70(3):459-466.


    [44] CLOKIE CM, URIST MR. Bone morphogenetic protein excipients: comparative observations on poloxamer

    [J]. Plast Reconstr Surg, 2000, 105(2):628-637.


    [45] CHO CW, CHO YS, LEE HK, et al. Improvement of receptor-mediated gene delivery to HepG2 cells using an amphiphilic gelling agent

    [J]. Biotechnol Appl Biochem, 2000, 32 (Pt 1):21-26.


    [46] NI X, CHENG A, LI J. Supramolecular hydrogels based on self-assembly between PEO-PPO-PEO triblock copolymers and alpha-cyclodextrin

    [J]. J Biomed Mater Res A, 2009, 88(4):1031-1036.


    [47] GUO DD, XU CX, QUAN JS, et al. Synergistic anti-tumor activity of paclitaxel-incorporated conjugated linoleic acid-coupled poloxamer thermosensitive hydrogel in vitro and in vivo

    [J]. Biomaterials, 2009, 30(27):4777-4785.


    [48] DING C, ZHAO L, LIU F, et al. Dually responsive injectable hydrogel prepared by in situ cross-linking of glycol chitosan and benzaldehyde-capped PEO-PPO-PEO

    [J]. Biomacromolecules, 2010, 11(4):1043-1051.


    [49] LI F, LI S, GHZAOUI AE, et al. Synthesis and Gelation Properties of PEG-PLA-PEG Triblock copolymers obtained by coupling monohydroxylated PEG-PLA with adipoyl chloride

    [J]. Langmuir, 2007, 23(5):2778-2783.


    [50] CALUCCI L, FORTE C, BUWALDA SJ, et al. Self-aggregation of gel forming PEG-PLA star block copolymers in Water

    [J]. Langmuir, 2010, 26(15):12890-12896.


    [51] TYAGI P, LI Z, CHANCELLOR M, et al. Sustained intravesical drug delivery using thermosensitive hydrogel

    [J]. Pharm Res, 2004, 21(5):832-837.


    [52] ARAKERI G, BRENNAN PA. Dose-dependent sustained local release of dexamethasone from biodegradable thermosensitive hydrogel of PEG-PLGA-PEG triblock copolymers in the possible prevention of TMJ re-ankylosis (Arakeri's TMJ release technique)

    [J]. Med Hypotheses, 2012, 78(5):682-686.


    [53] GONG C, SHI S, DONG P, et al. Synthesis and characterization of PEG-PCL-PEG thermosensitive hydrogel

    [J]. Int J Pharm, 2009, 365(1-2):89-99.


    [54] YANG B, GONG C, ZHAO X, et al. Preventing postoperative abdominal adhesions in a rat model with PEG-PCL-PEG hydrogel

    [J]. Int J Nanomedicine, 2012, 7:547-557.


    [55] ZHANG Z, NI J, CHEN L, et al. Biodegradable and thermoreversible PCLA-PEG-PCLA hydrogel as a barrier for prevention of postoperative adhesion

    [J]. Biomaterials, 2011, 32(21):4725-4736.


    [56] WANG CH, HSIUE GH. Synthesis and characterization of temperature- and pH-sensitive hydrogels based on poly (2-ethyl-2-oxazoline) and poly (D, L-lactide)

    [J]. J Polym Sci Poly Chem, 2002,40(8):1112-1121.


    [57] WANG CH, HSIUE GH. New amphiphilic poly (2-ethyl-2-oxazoline)/poly (L-lactide) triblock copolymers

    [J]. Biomacromolecules,2003, 4(6):1487-1490.


    [58] WANG X, LI X, LI Y, et al. Synthesis, characterization and biocompatibility of poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)-poly(2-ethyl-2-oxazoline) hydrogels

    [J]. Acta Biomater,2011, 7(12):4149-4159.


    [59] 赵宇,王晓波,张治然,等. 温敏凝胶的研究与应用进展

    [J]. 中国药房, 2015, 26(1):132-135.


    [60] 杨猛,周树柏,刘凤岐. 智能水凝胶的研究进展

    [J]. 化工科技, 2015, 23(1):66-71.


    [61] 孔明,程晓杰,陈西广.壳聚糖温敏水凝胶的质-构关系及研究进展

    [J]. 功能材料, 2014, 45(8):08007-08012.


    [62] 沈晶晶,刘宏,熊康萍. 温度敏感型凝胶基质的研究进展

    [J]. 中国新药杂志, 2015, 24(7):800-803,817.


    [63] ZHANG XZ, YANG YY, CHUNG TS, et al. Preparation and characterization of fast response macroporous poly (N-isopropylacrylamide) hydrogels

    [J]. Langmuir, 2001, 17(20):6094-6099.


    [64] LIU XM, WANG LS,  WANG L, et al. The effect of salt and pH on the phase-transition behaviors of temperature-sensitive copolymers based on N-isopropylacrylamide

    [J]. Biomaterials, 2004, 25(25):5659-5666.


    [65] 顼佳音,杨洪军,熊欣,等. 常见温度敏感型原位凝胶载体的研究进展

    [J]. 中国实验方剂学杂志, 2011, 17(2):252-257.


    [66] 马俊鹤,郭晨,唐亚林,等. PEO-PPO-PEO嵌段共聚物的NMR研究进展

    [J]. 波谱学杂志, 2008, 25(3):421-434


    [67] RUEL-GARIPY E, LEROUX JC. In situ-forming hydrogels-review of temperature-sensitive systems

    [J]. Eur J Pharm Biopharm, 2004, 58(2):409-426.


    [68] 王超君,卓阳,卢芳芳,等. 温敏凝胶材料成胶机制的研究进展

    [J]. 中国药房, 2013, 24(37):3545-3547.


    [69] YU L, ZHANG H, DING J. A subtle end-group effect on macroscopic physical gelation of triblock copolymer aqueous solutions

    [J]. Angew Chem Int Ed Engl, 2006, 45(14):2232-2235.


    [70] ZENTNER GM, RATHI R, SHIH C, et al. Biodegradable block copolymers for delivery of proteins and water-insoluble drugs

    [J]. J Control Release,2001, 72(1-3):203-215.


    [71] CHEN ZP, LIU W, LIU D, et al. Development of brucine-loaded microsphere/thermally responsive hydrogel combination system for intra-articular administration

    [J]. J Control Release, 2012, 162(3):628-635.


    [72] GAO Y, REN F, DING B, et al. A thermo-sensitive PLGA-PEG-PLGA hydrogel for sustained release of docetaxel

    [J]. J Drug Target, 2011, 19(7):516-527.


    [73] FANG JY, CHEN JP, LEU YL, et al. Temperature-sensitive hydrogels composed of chitosan and hyaluronic acid as injectable carriers for drug delivery

    [J]. Eur J Pharm Biopharm, 2008, 68(3):626-636.


    [74] TSAGARELI MG. Behavioral testing of the effects of thermosensitive TRP channel agonists on touch, temperature, and pain sensations

    [J]. Neurophysiology, 2011, 43(4):309-320.


    [75] QIAN S, WONG YC, ZUO Z. Development, characterization and application of in situ gel systems for intranasal delivery of tacrine

    [J]. Int J Pharm, 2014, 468(1-2):272-282.


    [76] WONG YC, ZUO Z. Brain disposition and catalepsy after intranasal delivery of loxapine: role of metabolism in PK/PD of intranasal CNS drugs

    [J]. Pharm Res, 2013, 30(9):2368-2384.


    [77] KOZLOVSKAYA L, ABOU-KAOUD M, STEPENSKY D. Quantitative analysis of drug delivery to the brain via nasal route

    [J]. J Control Release, 2014, 189(10):133-140.


    [78] SCANTAMBURLO G, HANSENNE M, GEENEN V,et al. Additional intranasal oxytocin to escitalopram improves depressive symptoms in resistant depression: an open trial

    [J]. Eur Psychiatry, 2015, 30(1):65-68.


    [79] ELNAGGAR YS, ETMAN SM, ABDELMONSIF DA, et al. Intranasal piperine-loaded chitosan nanoparticles as brain-targeted therapy in alzheimer's disease: optimization, biological efficacy, and potential toxicity

    [J]. J Pharm Sci, 2015, 104(10):3544-3556.


    [80] SIEGEL RA, KAPOOR M, CHERYALA N, et al. Water-soluble benzodiazepine prodrug/enzyme combinations for intranasal rescue therapies

    [J]. Epilepsy Behav, 2015, 49:347-350.


    [81] RODRGUEZ-NOGALES C, GARBAYO E, CARMONA-ABELLN MM, et al. Brain aging and Parkinson's disease: New therapeutic approaches using drug delivery systems

    [J]. Maturitas, 2016, 84:25-31.


    [82] BODDU SH, GUNDA S, EARLA R, et al. Ocular microdialysis: a continuous sampling technique to study pharmacokinetics and pharmacodynamicsin the eye

    [J]. Bioanalysis, 2010, 2(3):487-507.


    [83] BODDU SH, GUPTA H, BONAM SP. Preclinical evaluation of a ricinoleic acid poloxamer gel system for transdermal eyelid delivery

    [J]. Int J Pharm, 2014, 470(1-2):158-161.


    [84] BHOWMIK M, KUMARI P, SARKAR G, et al. Effect of xanthan gum and guar gum on in situ gelling ophthalmic drug delivery system based on poloxamer-407

    [J].Int J Biol Macromol, 2013, 62(11):117-123.


    [85] GRATIERI T, GELFUSO GM, DE FREITAS O, et al. Enhancing and sustaining the topical ocular delivery of fluconazole using chitosan solution and poloxamer/chitosan in situ forming gel

    [J]. Eur J Pharm Biopharm, 2011, 79(2):320-327.


    [86] HE ZX, WANG ZH, ZHANG HH, et al. Doxycycline and hydroxypropyl-b-cyclodextrin complex in poloxamer thermalsensitive hydrogel for ophthalmic delivery

    [J]. Acta Pharmaceutica Sinica B, 2011, 1(4):254-260.


    [87] 华晓东,任变文. 经皮给药系统的研究进展

    [J]. 现代药物与临床, 2009, 24(5):282-285.


    [88] 熊欣,刘淑芝,顼佳音,等. 新型载体经皮凝胶剂的研究进展

    [J]. 中国实验方剂学杂志, 2011, 17(22):244-249.


    [89] 夏裕发,褚克丹,李煌,等. 治疗类风湿性关节炎的中药经皮给药制剂研究概况

    [J]. 中医外治杂志, 2012, 21(1):44-46.


    [90] 罗穆潮,王冶闽,杨燕. 阿昔洛韦温敏凝胶的制备及评价

    [J]. 中国现代应用药学, 2012, 29(9):819-822.


    [91] FOUAD SA, BASALIOUS EB, EL-NABARAWI MA, et al. Microemulsion and poloxamer microemulsion-based gel for sustained transdermal delivery of diclofenac epolamine using in-skin drug depot: in vitro/in vivo evaluation

    [J]. Int J Pharm, 2013,453(2):569-578. 


    [92] 魏玉辉,张建萍,段好刚,等. 苦豆子总碱温敏凝胶的制备及体外评价

    [J]. 中成药, 2015,38(10):2318-2320.


    [93] 田芳,王玉柱,杨凯,等. 尼非韦罗阴道温敏原位凝胶的流变学研究

    [J].中国新药杂志, 2013, 22(3):345-350.


    [94] LU C, LIU M, FU H, et al. Novel thermosensitive in situ gel based on poloxamer for uterus delivery

    [J]. Eur J Pharm Sci, 2015, 77:24-28.


    [95] ZENG N, DUMORTIER G, MAURY M, et al. Influence of additives on a thermosensitive hydrogel for buccal delivery of salbutamol: relation between micellization, gelation, mechanic and release properties

    [J]. Int J Pharm, 2014, 467(1-2):70-83. 


    [96] CHANG EI, GALVEZ MG, GLOTZBACH JP, et al. Vascular anastomosis using controlled phase transitions in poloxamer gels

    [J]. Nat Med, 2011, 17(9):1147-1152.