Correa Tarcisio, Bazylinski Dennis A, Garcia Flávio, Abreu Fernanda
Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro Avenida Carlos Chagas Filho, 373, CCS, UFRJ Rio de Janeiro RJ 21941-902 Brazil
School of Life Sciences, University of Nevada at Las Vegas Las Vegas Nevada USA.
RSC Adv. 2021 Aug 18;11(45):28000-28007. doi: 10.1039/d1ra03950d. eCollection 2021 Aug 16.
Magnetotactic bacteria, which synthesize biological magnetite nanoparticles (BMs), are the main microbial source of magnetic nanomaterials. Although the use of BMs has been explored and for new anticancer formulations, targeted treatments of fungal and parasitic diseases would also benefit from biogenic magnetic nanoformulations. Due to the necessity of new formulations of amphotericin B, we developed a magnetic-nanoparticle based conjugate of this drug using bacterial magnetosomes. Different amphotericin B preparations were obtained using BMs extracted from strain MV-1 as well as glutaraldehyde and poly-l-lysine as linking reagents. The highest capture efficiencies and drug loadings were achieved using 0.1‰ poly-l-lysine as the only linking agent (52.7 ± 2.1%, and 25.3 ± 1.9 μg per 100 μg, respectively) and 0.1‰ poly-l-lysine and glutaraldehyde 12.5% (45.0 ± 5.4%, and 21.6 ± 4.9 μg per 100 μg, respectively). Transmission electron microscopy and infrared spectroscopy analyses confirmed the association of amphotericin B to the BM surface. Moreover, controlled drug release from these nanoparticles was achieved by applying an alternating magnetic field. In this condition the release of amphotericin B in PBS increased approximately four-fold as compared to the release under standard conditions with no applied magnetic fields. Hence, the functionalization of BMs with amphotericin B produces stable nanoformulations with a controllable drug release profile, thus, enabling its potential in the treatment of fungal and parasitic diseases.
合成生物磁铁矿纳米颗粒（BMs）的趋磁细菌是磁性纳米材料的主要微生物来源。尽管已经探索了BMs在新型抗癌制剂中的应用，但真菌和寄生虫疾病的靶向治疗也将受益于生物磁性纳米制剂。由于需要新型两性霉素B制剂，我们利用细菌磁小体开发了这种药物的基于磁性纳米颗粒的缀合物。使用从MV-1菌株中提取的BMs以及戊二醛和聚-L-赖氨酸作为连接试剂，获得了不同的两性霉素B制剂。使用0.1‰聚-L-赖氨酸作为唯一连接剂时，捕获效率和药物负载量最高（分别为52.7±2.1%和每100μg 25.3±1.9μg），使用0.1‰聚-L-赖氨酸和12.5%戊二醛时，捕获效率和药物负载量分别为45.0±5.4%和每100μg 21.6±4.9μg。透射电子显微镜和红外光谱分析证实了两性霉素B与BM表面的结合。此外，通过施加交变磁场实现了这些纳米颗粒的可控药物释放。在这种情况下，与无外加磁场的标准条件下相比，两性霉素B在PBS中的释放增加了约四倍。因此，用两性霉素B对BMs进行功能化可产生具有可控药物释放曲线的稳定纳米制剂，从而使其在治疗真菌和寄生虫疾病方面具有潜力。
