口腔医学研究

口腔医学研究 ›› 2016, Vol. 32 ›› Issue (7): 707-711.DOI: 10.13701/j.cnki.kqyxyj.2016.07.011

• 基础研究论著 • 上一篇    下一篇

载辛伐他汀羟基磷灰石中空微球的制备、表征及其用于盖髓剂的实验研究

王珂1,2, 赵旭3, 李毅1,2*, 张雪1,2, 王银晶1,2   

  1. 1. 吉林大学口腔医学院儿童口腔科 吉林 长春 130021;
    2. 吉林省牙发育及颌骨重塑与再生重点实验室 吉林 长春 1320021;
    3. 吉林大学化学学院 吉林 长春 130021
  • 收稿日期:2015-11-24 出版日期:2016-07-26 发布日期:2016-07-25
  • 通讯作者: 李毅,E-mail:lyi99@jlu.edu.cn
  • 作者简介:王珂(1988~ ),女,山东聊城人,硕士在读,主要从事儿童牙病的研究工作。
  • 基金资助:
    吉林省自然科学基金(20150101204JC);吉林省卫生计生委基金(2014Z064)

Preparation and Characterization of Hollow Hydroxyapatite Microspheres Loaded with Simvastatin as Pulp Capping Agent.

WANG Ke1,2, ZHAO Xu3, LI Yi1,2*, ZHANG Xue1,2, WANG Yin-jing1,2.   

  1. 1. Department of Pedodontics, School and Hospital of Stomatology, Jilin University, Changchun 130021, China;
    2. Provincial Key Laboratory of Tooth Development and Bone, Changchun 130021, China;
    3. School of Chemistry, Jilin University, Changchun 130021, China
  • Received:2015-11-24 Online:2016-07-26 Published:2016-07-25

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被引次数

2

摘要： 目的: 制备羟基磷灰石中空微球并载辛伐他汀,构成体外药物缓释系统检验其对损伤大鼠牙髓的修复作用。方法: 以谷氨酸(Glu)为有机质,以十二烷基磺酸钠(SDS)和Glu组成的“核-壳”式复合物作为模板,制备出中空羟基磷灰石(HHAp)微球。表征产物形貌并载药,计算载药率和包封率,测定药物体外释放情况。雄性大鼠建立上颌第一磨牙直接盖髓模型。左侧上颌第一磨牙分别覆盖含有10-5 mol/L ,10-7 mol/L和10-9 mol/L 辛伐他汀的载药羟基磷灰石中空微球。第1组右侧上颌第一磨牙用未载药的HHAp微球盖髓,其余不作处理。分别于术后7 d、28 d,每组随机处死5只大鼠取材,HE染色。用图像分析软件INH测定各组标本中修复性牙本质的面积比例,并采用SPSS17.0对数据进行Dunnett t检验和配对t检验。结果: 合成的羟基磷灰石为由短针状纳米粒子组成的直径为2~4 μm中空的微球。载药率为21.3%~46.0%,包封率为34.46%~46.02%。药物在载药微球中缓慢释放,释放曲线接近线性。将含有不同浓度辛伐他汀的载药微球盖髓7 d后,对照组穿髓孔下方炎症反应明显,实验组则表现出轻微的炎症反应;盖髓后28 d, 10-7 mol/L SIM组与对照组、10-5 mol/L SIM组及10-9 mol/L SIM组相比形成了较多修复性牙本质(P<0.05)。结论: 利用小分子有机质(Glu)和表面活性剂(SDS)为模板可以合成中空羟基磷灰石微球,且此微球载药率和包封率均较高;药物在其中释放接近线性,达到缓释要求;含有10-7 mol/L SIM的载药微球能够显著促进牙髓损伤后修复性牙本质的形成。

关键词: 中空羟基磷灰石, 辛伐他汀, 缓释, 牙髓, 损伤修复

Abstract: Objective: To synthesize hollow hydroxyapatite microspheres with favorable biocompatibility while loaded with simvastatin in order to constitute sustained-release system in vitro and examine the effect in the restoration of rat dental pulp. Methods: Based on the principle of biomimetic synthesis, hollow hydroxyapatite (HHAp) microspheres were successfully synthesized via the precipitation reaction utilizing glutamic acid (Glu) and sodium dodecyl sulfonate (SDS) “core-shell model” aggregates acting as templates. Morphology of the resultant was characterized and then loaded with simvastatin. Release in vitro of simvastatin was analyzed by UV spectrophotometry and then the cumulative rate curves of simvastatin were drawn. Thirty male Wistar rats were divided into three groups randomly and established the model of direct dental pulp capping of maxillary first molars. The drug loaded microspheres containing 10-5mol/L, 10-7mol/L and 10-9mol/L simvastatin were applied on the maxillary first molars on left side of the three groups respectively. The exposed pulps of the maxillary first molars on right of the first group were capped with HHAp microspheres without loading drug. The rest accepted no special treatment. On day 7 and 28 after operation, five rats of each group were sacrificed and stained with hematoxylin-eosin. The area rates of reparative dentin were calculated with NIH image software and analyzed by Dunnett t test and paired t test with SPSS 17.0 software. Results: The as-prepared HAp was hollow microspheres with diameter of 2-4 μm and was composed of many needle-like particles. The drug loading and encapsulation efficiency was 21.3%-46.0% and 34.46%-46.02%, respectively. The drug-loading release behavior in vitro followed the linear release. The inflammation under the perforation in group control was more obvious than experimental groups at day 7. A thicker layer of reparative dentin was formed in group 10-7mol/L than group control, 10-5mol/L and 10-9mol/L. Conclusion: The HHAp microspheres can be synthesized via Glu and SDS “core-shell model” aggregates acting as templates and the efficiency of drug loading and encapsulation is high. The release behavior follows the linear release. The drug loaded microspheres containing 10-7mol/L SIM may promote the repair of dental pulp after injury.

Key words: Hollow hydroxyapatite , Simvastatin , Sustained release, Dental pulp , Wound healing

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