Nicoletti Caroline Deckmann, Faria Ana Flávia Martins, de Sá Haddad Queiroz Marcella, Dos Santos Galvão Raíssa Maria, Souza André Luis Almeida, Futuro Débora Omena, Faria Robson Xavier, Ferreira Vitor Francisco
Departamento de Tecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal Fluminense, Niterói, RJ, 24241-000, Brazil.
Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Av. Brasil, n° 4365, Pavilhão Carlos Chagas, sala 208c, Manguinhos, Rio de Janeiro, RJ, 21045900, Brazil.
J Bioenerg Biomembr. 2020 Jun;52(3):185-197. doi: 10.1007/s10863-020-09826-8. Epub 2020 Mar 21.
We study βLAP and its derivative nor-β-Lapachone (NβL) complexes with 2-hydroxypropyl-β-cyclodextrin to increase the solubility and bioavailability. The formation of true inclusion complexes between βLAP or NβL in 2-HP-β-CD in solid solution was characterization by FT-IR, DSC, powder X-ray was and was confirmed by one- and two-dimensional H NMR experiments. Additionally, the biological activities of βLAP, NβL, ICβLAP, and ICNβL were investigated through trypanocidal assays with T. cruzi and cytotoxicity studies with mouse peritoneal macrophages. Originally, we tested these complexes against T. cruzi viability and observed higher biological activities and lower cytotoxicity when compared to βLAP and NβL. Thus, the complexation of βLAP and NβL with 2-HP-β-CD increases the drug solubility, in addition vectorization was observed, increasing the biological activity against epimastigotes and trypomastigotes T. cruzi forms. Reduced the toxicity of the compounds against mammalian cells. In addition, the selectivity indices higher of the inclusion complexes comparing to substance free and those of benznidazole.
我们研究了β-拉帕醇（βLAP）及其衍生物去甲-β-拉帕醌（NβL）与2-羟丙基-β-环糊精形成的复合物，以提高其溶解度和生物利用度。通过傅里叶变换红外光谱（FT-IR）、差示扫描量热法（DSC）、粉末X射线衍射对βLAP或NβL与2-羟丙基-β-环糊精（2-HP-β-CD）在固溶体中形成的真正包合物进行了表征，并通过一维和二维氢核磁共振实验得到了证实。此外，通过对克氏锥虫的杀锥虫试验和对小鼠腹腔巨噬细胞的细胞毒性研究，考察了βLAP、NβL、ICβLAP和ICNβL的生物活性。最初，我们测试了这些复合物对克氏锥虫活力的影响，与βLAP和NβL相比，观察到更高的生物活性和更低的细胞毒性。因此，βLAP和NβL与2-HP-β-CD的络合增加了药物的溶解度，此外还观察到了载体化现象，增强了对克氏锥虫前鞭毛体和锥鞭毛体形式的生物活性。降低了化合物对哺乳动物细胞的毒性。此外，包合物的选择性指数高于游离物质和苯硝唑。
