药物与载体材料相容性的预测方法研究  

Prediction method for the compatibility between drug and its carrier

作　　者：李平祝[1] 李馨儒[1] 周鹤翔[1] 张燕惠[1] 王菲[1] 刘艳[1] 

机构地区：[1]北京大学药学院药剂学系,北京100191

出　　处：《中国新药杂志》2009年第3期262-266,271,共6页Chinese Journal of New Drugs

摘　　要：目的:建立一种预测药物与载体材料相容性的方法。方法:采用基团贡献法(group-contributionmethod,GCM)分别计算药物紫杉醇(Paclitaxel,PTX)与载体材料聚乳酸[poly(DL-lactide),PLA]和聚乙交酯丙交酯[poly(DL-lactide-co-glycolide),PLGA]的部分溶解度参数;采用经典的傅立叶变换红外光谱(FourierTransform Infrared,FT-IR)与X射线粉末衍射(X-Ray Diffraction,XRD)法来评价药物与载体材料的相容性;采用旋转蒸发法制备聚合物胶束,用高效液相色谱法测定药物的含量。结果:溶解度参数的计算结果表明PTX与PLA的部分溶解度参数比PTX与PLGA的部分溶解度参数更接近,即PTX与PLA的相容性较PTX与PLGA的相容性好。FT-IR图谱显示PTX的特征峰1 646 cm-1在PTX与PLA的共沉淀混合物(3∶7,w/w)中位移至1 666 cm-1,而在与PLGA的相应混合物中位移至1 663 cm-1;XRD结果显示PTX特征衍射峰在PTX与PLA(3∶7,w/w)的共沉淀混合物中消失,而在与PLGA的相应混合物中仍然存在。PEG-PLA和PEG-PLGA胶束的载药量和包封率分别为(7.8±0.16)%,(84.6±1.91)%和(6.4±0.31)%,(68.5±3.53)%。上述结果进一步验证了溶解度参数的计算结果。结论:计算并比较紫杉醇与PLA和PLGA的部分溶解度参数可预测紫杉醇与PLA和PLGA的相容性,本方法可能是一种潜在的选择合适的药物载体材料的简便、快速、经济、有效的新方法。Objective：To establish a new method for predicting the compatibility between drug and its carrier materials. Methods： The partial solubility parameters for model drug of paclitaxel （PTX） and drug carrier materials of poly（DL-lactide） （PLA） and poly （DL-lactide-co-glycolide） （PLGA） were calculated using the group contribution method （ GCM）. Then physicochemical analysis of drug-drug carrier material pairs were pursued using classic physicocbemical techniques,including Fourier Transform Infrared （FT-IR） and X-Ray Diffraction （XRD）. Finally,PTX-loaded PEG-PLA and PEG-PLGA copolymer micelles were prepared, respectively, by rotary evaporation method. The drug content in the micelles was determined using HPLC method. Results：The calculation results for the difference of partial solubility parameters between PTX and the two copolymers showed that △δp （PLA, PTX） 〈 △δp （PLGA,PTX）, indicating that PTX was more compatible with PLA than with PLGA. In the FT-IR spectra,characteristic peak of PTX at 1 646 cm^-1 shifted to 1 666 cm^-1 in the physical mixtures of PTX and PLA （3： 7, w/w）, while 1 663 cm^-1 in the mixture of PTX and PLGA （ 3 ： 7, w/w）. XRD analysis showed that the diffraction peaks corresponding to the drug in the crystalline state disappeared in the physical mixture of PTX and PLA （3：7 ,w/w）, while the diffraction peaks were observed in the mixture of PTX and PLGA（3：7 ,w/w）. The loading content and encapsulation efficiency for PEG-PLA micelles were（7.8 ±0.16）%, （84.6 ± 1.91 ）%, and the drug loading content and encapsulation efficiency for PEG-PLGA copolymer micelles were （6.4 ± 0.31 ） % and （68.5 ± 3.53 ）% , respectively（ P 〈 0.03 ）. The compatibility was confirmed. Conclusion：By calculating and comparing of partial solubility parameters for PTX and the two polymers,the compatibility between the two polymers and PTX was successfully predicted. This method would be an easy, rapid, economical and efficient way

关 键 词：紫杉醇 聚乳酸 聚乙交酯丙交酯 药物载体 溶解度参数 相容性 

分 类 号：R913[医药卫生—药学] R979.1