用于改善吸收的甘草酸二铵/三甲基化壳聚糖纳米粒的制备和性质考察

Preparation and characteristics of diammonium glycyrrhizinate/trimethylated chitosan nanoparticles for improving absorption

目的制备甘草酸二铵（DG）/三甲基化壳聚糖（TMC）纳米粒并研究其基本性质。方法利用带正电荷的TMC与带负电荷的DG的静电相互作用制备DG/TMC纳米粒,以激光粒度测定仪和透射电镜（TEM）测定纳米粒的粒径和形态,以透析法测定纳米粒的释药度。结果 DG溶于p H 6.8~8.0的水中,浓度为50 g·L-1,TMC溶于p H 6.8~8.0的水中,浓度为30 g·L-1,室温下混合,温和搅拌,制得类球形DG/TMC纳米粒,平均粒径为72.8 nm,zeta电位为＋29.81 m V。在p H=1盐酸、p H=7磷酸盐缓冲液、0.9%Na Cl溶液和蒸馏水中24 h累计释放度依次为99.2%、89.6%、85.8%和35.6%,口服相对生物利用度为220%,半衰期明显延长。结论 DG/TMC纳米粒制备方法简单可行,其释放行为与释放介质的离子强度及种类有关,具有缓释特点,能够改善DG的口服吸收。

Objective To prepare diammonium glycyrrhiziate/trimethylated chitosan （DG/TMC） nanoparticles and investigate the basic characteristics of the nanoparticles. Methods DG/TMC nanoparticles were prepared based on the electrostatic interaction between TMC with positive charges and DG with negative charges. Transmission electron mi- croscope and laser scattering particle analyzer were used to determine the average particle size. Dialysis method was used to measure the accumulative drug release. Results 50 goL 1DG and 30 g·L- 1 TMC were dissolved in water （pH 6.8 - 8.0）, respectively. The 2 solutions were mixed moderately at room temperature. DG/TMC nanoparticles were spherical, the average particles size was 72.8 nm, and the zeta potential was ＋ 29.81 mV. The accumulative drug release during 24 h in pH = 1 HCI, pH = 7 PBS, 0.9% NaCl and distilled water was 99.2%, 89.6%, 85.8% and 35.6%, respectively. The relative bioavailability was 220%. Oral half life was prolonged obviously. Conclusion The preparation of DG/TMC nanoparticles is simple and practicable. The drug release behavior is ralated to the ionic strength of the medium and ionic types and sustained release characteristics in some conditions. DG/TMC nanoparticles can improve the oral absorption of DG.