载高乌甲素可注射壳聚糖/β-甘油磷酸钠温敏水凝胶的制备与性能研究

马君义,陈香玲,盛爱霞,邱雅静,梁艳丽,张继

中国药学杂志 ›› 2015, Vol. 50 ›› Issue (19) : 1696-1703.

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中国药学杂志 ›› 2015, Vol. 50 ›› Issue (19) : 1696-1703. DOI: 10.11669/cpj.2015.19.010
论著

载高乌甲素可注射壳聚糖/β-甘油磷酸钠温敏水凝胶的制备与性能研究

  • 马君义1,2,陈香玲1,盛爱霞1,邱雅静1,梁艳丽1,张继1,2
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Preparation of Lappaconitine-Loaded Chitosan/Sodium β-Glycerophosphate Injectable Thermosensitive Hydrogels and Research on Its Properties

  • MA Jun-yi1,2, CHEN Xiang-ling1, SHENG Ai-xia1,QIU Ya-jing1,LIANG Yan-li1,ZHANG Ji1,2
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摘要

目的 制备载高乌甲素(LA)的壳聚糖/β-甘油磷酸钠(CS/β-GP)温敏水凝胶,并研究其凝胶形成的相转变机制和体外释药性能。方法 以生物可降解壳聚糖为载体,以β-甘油磷酸钠为促凝剂制备载高乌甲素可注射壳聚糖/β-甘油磷酸钠温敏水凝胶,采用动态透析法考察其体外释药性能,运用流变学方法研究凝胶形成的相转变机制。结果 优化的制备载高乌甲素可注射壳聚糖/β-甘油磷酸钠温敏水凝胶的工艺条件为:β-甘油磷酸钠质量浓度560 mg·mL-1、壳聚糖质量浓度22 mg·mL-1、酸溶剂为0.1 mol·L-1冰乙酸、壳聚糖/β-甘油磷酸钠体积比8.75∶1.25,在37 ℃下其凝胶化时间为338 s。壳聚糖/β-甘油磷酸钠水凝胶对高乌甲素具有缓释作用,其释药行为符合Higuchi模型和Korsmeyer-Peppas模型,为溶散释放。流变学研究表明,壳聚糖/β-甘油磷酸钠温敏水凝胶属于触变体系,具有类似非牛顿流体的剪切变稀的性质,表现出一种“类固体”的凝胶行为。结论 成功制备了具有较好弹性及强度的载高乌甲素可注射壳聚糖/β-甘油磷酸钠温敏水凝胶,且其体外释药具有明显的缓释特征。

Abstract

OBJECTIVE To prepare lappaconitine(LA)-loaded chitosan/ sodium β-glycerophosphate(CS/β-GP) thermosensitive hydrogels and investigate its phase transition mechanism of gel formation process and release properties in vitro. METHODS The injectable CS/β-GP thermosensitive hydrogels were prepared with biodegradable CS as carrier material and β-GP as coagulation accelerator. The release behavior in vitro was studied by dynamic dialysis, and the phase transition mechanism of gel formation process was further investigated by rheological method. RESULTS The optimized process condition was as follows:the concentration of β-GP and CS was 560 and 22 mg·mL-1, respectively, CS was dissolved by 0.1 mol·L-1 HOAc, and the valume ratio of CS to β-GP was 8.75∶1.25(V/V), the gelation time of CS/β-GP thermosensitive hydrogels with volume ratio of 8.75∶1.25(V/V) at 37 ℃ was 5 min 38 s. The in vitro release study showed that these injectable CS/β-GP thermosensitive hydrogels had sustained release effect for LA, and the release behavior could be well described by the Higuchi model and Korsmeyer-Peppas model. The mechanism of LA releasing from CS/β-GP thermosensitive hydrogels was attributed to drug dissolution and diffusion. Rheological studies showed that the CS/β-GP thermosensitive hydrogels belonged to thixotropic system and exhibited non-Newtonian and shear-thinning fluid behavior as well as “solid-like” gelatin behavior. CONCLUSION LA-Loaded CS/β-GP injectable thermosensitive hydrogels with good elasticity and gel strength properties are prepared successfully, and they show sustained release effect of LA in vitro.

关键词

温敏水凝胶 / 壳聚糖 / β-甘油磷酸钠 / 高乌甲素

Key words

hydrogel / chitosan(CS) / sodium β-glycerophosphate(β-GP) / lappaconitine

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导出引用
马君义,陈香玲,盛爱霞,邱雅静,梁艳丽,张继. 载高乌甲素可注射壳聚糖/β-甘油磷酸钠温敏水凝胶的制备与性能研究[J]. 中国药学杂志, 2015, 50(19): 1696-1703 https://doi.org/10.11669/cpj.2015.19.010
MA Jun-yi, CHEN Xiang-ling, SHENG Ai-xia,QIU Ya-jing,LIANG Yan-li,ZHANG Ji. Preparation of Lappaconitine-Loaded Chitosan/Sodium β-Glycerophosphate Injectable Thermosensitive Hydrogels and Research on Its Properties[J]. Chinese Pharmaceutical Journal, 2015, 50(19): 1696-1703 https://doi.org/10.11669/cpj.2015.19.010
中图分类号: R944   

参考文献

[1] ZHOU X M, SUN X R. Research progress of thermo-and pH-sensitive hydrogels [J]. Chem World(化学世界), 2013, 54(12):747-750.
[2] KANG C Z, CHENG X J, CHEN X G. The progress and application of thermo sensitive hydrogel based on chitosan and its derivatives [J]. Nat Prod Res Dev(天然产物研究与开发), 2010, 22(5):919-927.
[3] CHENITE A, BUSCHMANN M, WANG D, et al. Rheological characterisation of thermogelling chitosan/glycerol-phosphate solutions[J]. Carbohydr Poly, 2001, 46(1):39-47.
[4] PARK H, CHOI B, HU J, et al. Injectable chitosan hyaluronic acid hydrogels for cartilage tissue engineering[J]. Acta Biomater, 2013, 9(1):4779-4786.
[5] GIRI T K, 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(药学学报B), 2012, 2(5):439-449.
[6] NAZAR H, FATOUROS D G, VAN DER MERWE S M, et al. Thermo sensitive hydrogels for nasal drug delivery:The formulation and characterisation of systems based on N-trimethyl chitosan chloride[J]. Eur J Pharm Biopharm, 2011, 77(2):225-232.
[7] HSIAO M, LARSSON M, LARSSON A, et al. Design and characterization of a novel amphiphilic chitosan nanocapsule-based thermo-gelling biogel with sustained in vivo release of the hydrophilic anti-epilepsy drug ethosuximide[J]. J Controlled Release, 2012, 161(3):942-948.
[8] JIANG L X, LI Z, DONG J X, et al. Preparation and the temperature sensitivity research of chitosan hydrogel[J]. Shanghai J Biomed Engin(上海生物医学工程杂志), 2002, 23(2):19-21.
[9] CHO J, HEUZEY M, BGIN A, et al. Chitosan and glycerophosphate concentration dependence of solution behaviour and gel point using small amplitude oscillatory rheometry[J]. Food Hydrocolloids, 2006, 20(6):936-945.
[10] LIN Y W, FANG Y Y, MENG X D. Temperature sensitivity and sustained drug release of chitosan hydrogel[J]. J Fujian Med Univ(福建医科大学学报), 2009, 43(1):37-41.
[11] ZHANG J, CHU L Y, ZHANG S B, et al. Preparation and properties of biodegradable chitosan carriers with thermo-/pH-sensitive controlled-release characteristics[J]. J Sichuan Univ(四川大学学报), 2006, 38(1):54-58.
[12] QIANG Z. Study on temperature-sensitive chitosan hydrogel prepared in mixed acid [J]. Chem World(化学世界), 2010, 51(8):470-472.
[13] RUEL-GARIPY E, CHENITE A, CHAPUT C, et al. Characterization of thermosensitive chitosan gels for the sustained delivery of drugs[J]. Int J Pharm, 2000, 203(1-2):89-98.
[14] ROSSI S, MARCIELLO M, BONFERONI M C, et al. Thermally sensitive gels based on chitosan derivatives for the treatment of oral mucositwas[J]. Eur J Pharm Biopharm, 2010, 74(2):248-254.
[15] ZHANG Y, HUO M R, ZHOU J P, et al. DDSolver:An add-in program for modeling and comparison of drug dissolution profiles[J]. The AAPS J, 2010, 12(3):263-271.
[16] GAO C, CAI Y, KONG X, et al. Development and characterization of injectable chitosan-based hydrogels containing dexamethasone/rhBMP-2 loaded hydroxyapatite nanoparticles[J]. Mater Lett, 2013, 93:312-315.
[17] ZHANG X Y, ZHU B, GU Q S. Effect of deacetylation degree of chitosan on thermosensitive hydrogel via rheological characterization[J]. Chin J Repar Reconstr Surg(中国修复重建外科杂志),2008,22(7):861-863.
[18] YU J, LIU S X, FANG Y, et al. Study on mechanical performance of PDMAEMA hydrogel with pH and temperature sensitivity[J]. J Shanxi Normal Univ(陕西师范大学学报), 2010, 38(3):50-55.
[19] MA J Y, LIN Y B, JIANG Y F, et al. Analysis of flowability, thixotropy and dynamic viscoelastic of Gum Arabic solution[J]. Sci Technol Food Ind(食品工业科技), 2013, 34(19):77-79.
[20] MA J Y, LIN Y B, CHEN X L, et al. Flow behavior, thixotropy and dynamical viscoelasticity of sodium alginate aqueous solutions[J]. Food Hydr, 2014, 38:119-128.
[21] HUANG C L, FANG B, CHENG W, et al. Preparation and rheological properties of different molecules of degraded chitosan/degraded carrageenan gels[J].Food Sci Technol(食品科技), 2007, 32(4):27-31.

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兰州市科技计划资助项目(2012-2-92)
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