Laboratório de Tecnologia dos Medicamentos (LTM), Department of Pharmaceutical Sciences, Federal University of Pernambuco, Av. Prof. Arthur de Sá, s/n, Cidade Universitária, 50740-521, Recife, PE, Brazil.
Laboratório de Terras Raras (BSTR), Fundamental Departament of Chemistry, Federal University of Pernambuco, Av. Jornalista Aníbal Fernandes, s/n - Cidade Universitária, 50740-560, Recife, PE, Brazil.
J Mater Sci Mater Med. 2021 May 17;32(6):59. doi: 10.1007/s10856-021-06530-w.
Chagas disease is a neglected tropical disease caused by the flagellate protozoan Trypanosoma cruzi (T. cruzi). Endemic in underdeveloped and developed countries, due to the migratory movement, it is considered a serious public health problem. Endemic in underdeveloped countries and due to the migratory movement, in developed countries as well, it is considered a serious public health problem. One of the reasons for this is a weak therapeutic arsenal, represented only by the drug benznidazole (BNZ) which, although it promotes significant cure rates in the acute phase of the disease, presents serious problems of toxicity and bioavailability, mainly due to its low aqueous solubility. Several studies have presented several drug delivery systems (DDS) based on BNZ aiming at enhancing its solubility in aqueous medium and, with this, promoting an increase in the dissolution rate and, consequently, in its bioavailability. However, the present work is a pioneer in using a zeolitic imidazolate framework as a carrier agent for a DDS in order to promote a pH-sensitive modulation of the drug. Thus, this work aimed to develop a novel DDS based on BNZ and the ZIF-8 to use it in development of prolonged-release dosage forms to alternative treatment of Chagas disease. The BNZ@ZIF-8 system was obtained through an ex situ method selected due to its higher incorporation efficiency (38%). Different characterization techniques corroborated the obtainment and drug release data were analyzed by in vitro dissolution assay under sink and non-sink conditions and setting the kinetic results through both model dependent and independent methods. Under sink conditions, at pH 4.5, BNZ and BNZ@ZIF-8 showed similar release profile, but the DDS was effective in promoting a prolonged release. At pH 7.6, after 7 h, BNZ showed a lower release than BNZ@ZIF-8. On the other hand, in non-sink conditions at pH 4.5 the BNZ presented 80% of drug release in 3 h, while the DDS in 6 h. At pH 7.6, BNZ presented a release of 80% in 2 h, while the DDS reaches it in only at 12 h. Therefore, at pH 4.5 the DDS BNZ@ZIF-8 showed a faster release with a burst effect, while at pH 7.6 it showed a prolonged and controlled release. Finally, it is evident that a promising DDS pH-sensitive was obtained as a novel carrier that might be able to prolongs BNZ release in dosage forms intended for the alternative treatment of Chagas disease.
恰加斯病是一种被忽视的热带病，由鞭毛原生动物克氏锥虫（Trypanosoma cruzi，T. cruzi）引起。这种疾病在不发达国家和发达国家都有流行，由于人口迁移，它被认为是一个严重的公共卫生问题。在不发达国家流行，由于人口迁移，在发达国家也是如此，它被认为是一个严重的公共卫生问题。原因之一是治疗方法有限，只有苯硝唑（benznidazole，BNZ）这一种药物，尽管它在疾病的急性阶段能显著治愈，但存在严重的毒性和生物利用度问题，主要是由于其低水溶性。许多研究已经提出了几种基于 BNZ 的药物传递系统（drug delivery systems，DDS），旨在提高其在水介质中的溶解度，并由此提高溶解速率，进而提高其生物利用度。然而，本工作是使用沸石咪唑酯骨架作为载体剂来促进药物 pH 敏感性调节的先驱。因此，本工作旨在开发一种基于 BNZ 和 ZIF-8 的新型 DDS，用于开发延长释放剂型，以替代治疗恰加斯病。BNZ@ZIF-8 系统是通过一种由于其更高的结合效率（38%）而被选择的原位方法获得的。不同的特征化技术证实了获得，并通过体外溶出度试验在溶出和非溶出条件下分析了药物释放数据，并通过模型相关和独立的方法设置了动力学结果。在溶出条件下，在 pH 4.5 时，BNZ 和 BNZ@ZIF-8 表现出相似的释放曲线，但 DDS 有效地促进了延长释放。在 pH 7.6 时，7 小时后，BNZ 的释放低于 BNZ@ZIF-8。另一方面，在 pH 4.5 的非溶出条件下，BNZ 在 3 小时内释放了 80%的药物，而 DDS 在 6 小时内释放了 80%的药物。在 pH 7.6 时，BNZ 在 2 小时内释放了 80%的药物，而 DDS 则在 12 小时后才达到这一水平。因此，在 pH 4.5 时，DDS BNZ@ZIF-8 表现出更快的释放，具有爆发效应，而在 pH 7.6 时，它表现出延长和控制释放。最后，显然获得了一种有前途的 pH 敏感的 DDS，作为一种新型载体，可以延长苯硝唑在用于替代治疗恰加斯病的剂型中的释放。
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