苯妥英钠羧甲基壳聚糖缓释微球的制备及其对牙周常见致病菌的抑菌效果研究

Preparation of Phenytoin Sodium Carboxymethyl Chitosan Microsphere and Its Bacteriostasis Experiment Research on Periodontal Common Pathogenic Bacteria

关键词:  牙周致病菌  苯妥英钠  羧甲基壳聚糖微球  缓释

Key words:  periodontal tissue regeneration  phyenytoin  CMCS  slow release

摘要:

目的 采用正交试验法优化制备苯妥英钠羧甲基壳聚糖微球（PHT-CMCS-MS）的处方，观察其组分对2种牙周常见致病菌的抑菌效果。方法 采用乳化化学交联固化法制备PHT-CMCS-MS，以载药量、包封率为指标，采用正交试验设计优化制备工艺，观察载药微球表面形态，测定微球的释药性能及初步稳定性。并采用洞-平板法对牙周常见致病菌牙龈卟啉单胞菌和伴放线放线杆菌进行抑菌实验对比，以抑菌圈直径作纵横向比较，分析药物影响。结果 制备的PHT-CMCS-MS外观形态圆整，粒径分布较均匀，粒径分布范围为0.8~12µm，载药量为8.2%，包封率为48.9%，PHT-CMCS-MS在PBS（pH=7.3）的溶液中具有明显缓释效果。体外抑菌试验结果显示较高浓度的羧甲基壳聚糖、苯妥英钠及其缓释微球对Pg、Aa生长均有不同程度的抑菌作用。结论 结合苯妥英钠及羧甲基壳聚糖良好的生物活性及抑菌作用，制备载药微球缓释作用良好，可结合手术或局部注射辅助应用于牙周治疗，达到促进牙周组织再生的目的。

Abstract:

OBJECTIVE To optimize the preparation of phenytoin sodium carboxymethyl chitosan microspheres (PHT-CMCS-MS) using orthogonal test method, and to analyze the components' bacteriostatic effects of two common pathogenic bacteria of periodontal. METHODS The preparation of PHT-CMCS-MS used emulsion chemical cross-linking method and orthogonal test method, with drug loading and entrapment efficiency as index, preparation technology was optimized. Then surfaces of the microspheres were observed, release property and preliminary stability of the microspheres was determined. The bacteriostatic test with common periodontal pathogens (Pg and Aa) was carried out by hole-plate method. The effect of drug was analyzed by comparing the diameter of antibacterial circle. RESULTS The morphologic results showed that the PHT-CMCS-MS appearance in round shape and the particle size distribution range was 0.8-12 µm. The drug-loading rate was 8.2% and entrapment efficiency was 48.9%. The PHT-CMCS-MS in PBS (pH=7.3) had obvious sustained-release effect in solution. The results of in vitro antibacterial test showed that higher concentration of carboxymethyl chitosan, phenytoin and its sustained release microspheres had different bacteriostatic effects on the growth of Pg and Aa. CONCLUSION Combined with biological activity and antimicrobial effect of phenytoin sodium and carboxymethyl chitosan, PHT-CMCS-MS showes a good sustained release effect. It can be combined with surgery or local injections of auxiliary used in periodontal treatment, achieve the goal of periodontal tissue regeneration.