Núcleo de Espectroscopia e Estrutura Molecular, Departamento de Química, Universidade Federal de Juiz de Fora, Campus Universitário s/n, Martelos, Juiz de Fora, MG, 36036-900, Brazil.
Int J Pharm. 2012 Dec 15;439(1-2):207-15. doi: 10.1016/j.ijpharm.2012.09.039. Epub 2012 Sep 25.
Pentamidine isethionate (PNT) is an antiprotozoal active in many cases of leishmaniasis, despite the present limitations including high toxicity and parenteral administration. In the present work, a PNT encapsulation strategy into β-cyclodextrin cavity at 1:1 and 2:1 (βCD:PNT) molar ratios was used in order to improve the drug's physical and chemical properties. Combining thermodynamic and structural approaches such as isothermal titration calorimetry (ITC), electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance ((1)H NMR, and ROESY) the inclusion process and the thermodynamics parameters were identified. ITC and ESI-MS experimental data suggest the simultaneous formation of different supramolecular complexes in solution. Moreover, NMR data are in accordance with these results, suggesting a deep inclusion of PNT into the βCD cavity, through correlations observed in 2D ROESY contour maps. The systems were also characterized by FTIR, TG/DTA and SEM. These techniques indicate the formation of inclusion complex in the solid state. In vivo PNT activity was evaluated orally in mice. The inclusion complex showed a significant reduction of parasite load compared to free PNT.
戊二脒乙磺酸盐（PNT）是一种抗原生动物药物，在许多利什曼病病例中都有疗效，尽管目前存在毒性高和需要注射给药等局限性。在本工作中，采用了 PNT 与 β-环糊精以 1:1 和 2:1（βCD:PNT）摩尔比包合的策略，以改善药物的物理化学性质。通过等温滴定量热法（ITC）、电喷雾质谱（ESI-MS）和核磁共振（（1）H NMR 和 ROESY）等热力学和结构方法的结合，确定了包合过程和热力学参数。ITC 和 ESI-MS 实验数据表明，在溶液中同时形成了不同的超分子配合物。此外，NMR 数据与这些结果一致，表明 PNT 通过在 2D ROESY 轮廓图中观察到的相关性，被深度包合到βCD 空腔中。该体系还通过傅里叶变换红外光谱（FTIR）、热重分析/差示扫描量热法（TG/DTA）和扫描电子显微镜（SEM）进行了表征。这些技术表明在固态形成了包合物。体内实验中，通过口服给药方式在小鼠中评估了 PNT 的活性。与游离 PNT 相比，包合物显著降低了寄生虫载量。
