Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos 6627, Campus Pampulha, Belo Horizonte, Minas Gerais 31270-901, Brazil.
Laboratório de Desenvolvimento Galênico e Nanotecnologia - Escola de Farmácia, Universidade Federal de Ouro Preto, Campus Universitário - Morro do Cruzeiro, 35400-000, Ouro Preto, Minas Gerais, Brazil.
Biomed Pharmacother. 2018 Mar;99:438-444. doi: 10.1016/j.biopha.2018.01.021. Epub 2018 Feb 20.
Candida spp is an etiologic agent of fungal infections in hospitals and resistance to treatment with antifungals has been extensively reported. Thus, it is very important to develop formulations that increase effectiveness with low toxicity. In this sense, nanocarriers have been investigated, once they modify drug biodistribution profile. Thus, this study aimed to evaluate the biodistribution of free and encapsulated Tc-fluconazole into nanocapsules (NCs) in an experimental immunosuppressed murine model of Candida albicans infection.
Fluconazole was radiolabeled with technetium-99 metastable (Tc) and encapsulated into conventional (Tc-Fluconazole-PLA-POLOX) and surface-modified (Tc-Fluconazole-PLA-PEG) NCs by the interfacial deposition of the preformed biodegradable polymer [poly (D,L-lactic acid) (PLA) and PLA-PEG (polyethyleneglycol)] followed by solvent evaporation. The size distribution and zeta potential of the NCs preparations were determined in a Zetasizer by photon correlation spectroscopy and laser Doppler anemometry, respectively. Free and encapsulated Tc-fluconazole were administered intravenously in immunosuppressed mice bearing a local infection induced by Candida Albicans inoculation in the right thigh muscle. At pre-established time intervals, tissues and organs of interest were removed and radioactivity was measured in an automatic gamma radiation counter.
The NCs diameter was between 200 and 400 nm with negative zeta potential values. Free Tc-fluconazole was more rapidly eliminated by the renal system compared to the encapsulated drug in NCs, which remained longer in blood circulation. The uptake of conventional NCs by mononuclear phagocyte system organs was higher than the one demonstrated by the surface-modified NCs. Both NCs remained longer in the infectious focus when compared to free Tc-fluconazole, but the results did not show a significant difference between NC formulations.
These data indicate that these NCs might represent a therapeutic alternative for the treatment of candidiasis, once they remain more time in the infectious focus, allowing high retention of Tc-fluconazole at this site.
念珠菌属是医院真菌感染的病原体，并且对抗真菌药物的治疗已经有广泛的耐药性报道。因此，开发能够提高疗效且毒性低的制剂非常重要。在这方面，已经研究了纳米载体，因为它们可以改变药物的生物分布特征。因此，本研究旨在评估游离和包封的 Tc-氟康唑在白色念珠菌感染的实验性免疫抑制小鼠模型中的纳米囊（NC）中的生物分布。
氟康唑用锝-99 亚稳态（Tc）放射性标记，并通过界面沉积预先形成的可生物降解聚合物[聚（D，L-乳酸）（PLA）和 PLA-PEG（聚乙二醇）]将其包封到常规（Tc-氟康唑-PLA-POLOX）和表面修饰的（Tc-氟康唑-PLA-PEG）NC 中，然后通过溶剂蒸发。通过光子相关光谱法在 Zetasizer 中测定 NC 制剂的粒径分布和zeta 电位，通过激光多普勒动度计分别测定。游离和包封的 Tc-氟康唑通过静脉内给药给予患有白色念珠菌接种于右大腿肌肉引起的局部感染的免疫抑制小鼠。在预先设定的时间间隔内，取出感兴趣的组织和器官，并在自动伽马辐射计数器中测量放射性。
NC 的直径在 200 至 400nm 之间，zeta 电位值为负。与包封在 NC 中的药物相比，游离 Tc-氟康唑更快地通过肾脏系统消除，在血液循环中停留时间更长。单核吞噬细胞系统器官对常规 NC 的摄取高于表面修饰的 NC。与游离 Tc-氟康唑相比，两种 NC 都在感染灶中停留时间更长，但两种 NC 制剂之间的结果没有显示出显著差异。
这些数据表明，这些 NC 可能代表一种治疗念珠菌病的治疗选择，因为它们在感染灶中停留时间更长，从而允许在该部位保留更多的 Tc-氟康唑。
