Danafar H, Manjili H K, Najafi M
Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
Pharmaceutical Nanotechnology Department, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
Drug Res (Stuttg). 2016 Sep;66(9):495-504. doi: 10.1055/s-0042-110931. Epub 2016 Jul 19.
Enalapril was used for hypertension and congestive heart failure. Di-block mPEG-PCL copolymers were synthesized and used to prepare of polymersomes for controlled release of enalapril as a hydrophilic drug. The various methods such as HNMR, FTIR, GPC, DSC, PCS and AFM performed for characterization of the polymersomes. The results of AFM showed that the polymersomes had spherical structure and the size of nanoparticles was 97 nm. Drug-loading efficiency of nanoparticles from copolymers with compositions of mPEG1-PCL1, mPEG2-PCL2, and mPEG3-PCL3 were 14.43%, 19.8%, and 12.33% respectively. The release profile of enalapril for drug loaded nanoparticles prepared from mPEG3-PCL3 was very fast and release profile for the nanoparticles prepared from mPEG1-PCL1 and mPEG2-PCL2 was sustained. The IC value of enalapril was determined to be 8 μM while EPM/m-PEG-PCL nanoparticles did not show significant toxicity at equal concentrations in comparison with enalapril drug. Therapeutic preparations of mPEG-PCL micelle are calibrated by the mouse LD assay. A dose-finding scheme of the polymeric micelle showed a safe dose of mPEG-PCL micelles was approximately 330 mg/kg in mice. The relationship between the numbers of animals, number of doses, duration of the assay used to estimate the LD and the precision of the assay were investigated. Overall, the results was showed that m-PEG-PCL polymersomes can be considered as a promising carrier for hydrophilic drugs.
依那普利用于治疗高血压和充血性心力衰竭。合成了二嵌段甲氧基聚乙二醇-聚己内酯（mPEG-PCL）共聚物，并用于制备聚合物囊泡，以实现亲水性药物依那普利的控释。采用核磁共振氢谱（HNMR）、傅里叶变换红外光谱（FTIR）、凝胶渗透色谱（GPC）、差示扫描量热法（DSC）、光子相关光谱（PCS）和原子力显微镜（AFM）等多种方法对聚合物囊泡进行表征。原子力显微镜结果表明，聚合物囊泡具有球形结构，纳米颗粒尺寸为97纳米。由mPEG1-PCL1、mPEG2-PCL2和mPEG3-PCL3组成的共聚物制备的纳米颗粒的载药效率分别为14.43%、19.8%和12.33%。由mPEG3-PCL3制备的载药纳米颗粒的依那普利释放曲线非常快，而由mPEG1-PCL1和mPEG2-PCL2制备的纳米颗粒的释放曲线是持续的。依那普利的半数抑制浓度（IC）值测定为8微摩尔，而在相同浓度下，依那普利-甲氧基聚乙二醇-聚己内酯（EPM/m-PEG-PCL）纳米颗粒与依那普利药物相比未显示出明显毒性。通过小鼠半数致死量（LD）试验对甲氧基聚乙二醇-聚己内酯胶束的治疗制剂进行校准。聚合物胶束的剂量探索方案表明，小鼠中甲氧基聚乙二醇-聚己内酯胶束的安全剂量约为330毫克/千克。研究了用于估计LD的动物数量、剂量数量、试验持续时间与试验精度之间的关系。总体而言，结果表明甲氧基聚乙二醇-聚己内酯聚合物囊泡可被视为亲水性药物的一种有前景的载体。
