环糊精衍生物对胸腺喷丁微球突释效应的影响

Influence of Cyclodextrin Derivatives on Burst Release of Thymopentin Microspheres

先将疏水性三乙酰基--环糊精(TA--CD)和亲水性羟丙基--环糊精(HP--CD)分别与胸腺喷丁(1)制得共冻干复合物,再采用s/o/w乳化-溶剂挥发法以乳酸-羟基乙酸共聚物(PLGA)为载体制成缓释微球,比较环糊精衍生物对1-PLGA微球载药量、包封率和突释效应的影响,并初步探讨其降低突释效应的机制。结果表明,1-PLGA微球和1-TA--CD-PLGA微球的粒径、载药量、包封率和突释率(即24 h累积释放率)分别为(62.6±1.2)和(33.9±1.1)m、(6.37±0.22)%和(8.59±0.19)%、(57.4±0.8)%和(80.4±0.6)%、32.7%和15.2%。而1-HP--CD-PLGA微球与1-PLGA微球相比,载药量和包封率反而有所降低,且突释效应未见明显改善。冷场发射扫描电镜、差示扫描量热法和X-射线粉末衍射分析结果表明,在1-TA--CD共冻干过程中存在晶型转变,提示药物和辅料间可能发生了相互作用,阻止了1的扩散。

Hydrophobic triacetyl-β-cyclodextrin （TA-β-CD） and hydrophilic hydroxypropyl-β-cyclodextrin （HP-β-CD） were respectively co-lyophilized with thymopentin （1）. Then the sustained-release microspheres were prepared by s/o/w emulsion-solvent evaporation method with polylactic-co-glycolic acid （PLGA） as carrier material and 1 or its co-lyophilized complex as model drug. The effects of cyclodextrins on drug loading, encapsulation efficiency and burst effect of the above three kinds of 1-PLGA microspheres were compared and the mechanism of cyclodextrins to reduce the burst effect was preliminarily discussed. The results showed that the diameter, drug loading, encapsulation efficiency and burst effect （cumulative amount at 24 h） of 1-PLGA microspheres and 1-TA-13-CD-PLGA microspheres were （62.6±1.2） and （33.9±1.1）μm, （6.37±0.22） % and （8.59±0.19） %, （57.4±0.8） % and （80.4±0.6） %, 32.7% and 15.2 %, respectively. However, compared with 1-PLGA microspheres, the drug loading and encapsulation efficiency of 1-HP-β-CD-PLGA microspheres were decreased and the burst effect were not significantly improved. The results of cold field scanning electron microscope, differential scanning calorimetry and powder X-ray diffraction showed that the crystal composition was changed during the co-lyophilizing process, which suggested that there had been an interaction between 1 and TA-β-CD. It might hinder the diffusion of 1 from the microspheres.