de Assis Danielle Nogueira, Mosqueira Vanessa Carla Furtado, Vilela José Mário Carneiro, Andrade Margareth Spangler, Cardoso Valbert Nascimento
Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627 Belo Horizonte, MG 31270-901, Brazil.
Int J Pharm. 2008 Feb 12;349(1-2):152-60. doi: 10.1016/j.ijpharm.2007.08.002. Epub 2007 Aug 11.
Several classes of antifungal have been employed in candidiasis treatment, but patients with advanced immunodeficiency can present unsatisfactory results after therapy. In these cases, high doses of drugs or the use of multiple agents are sometimes used, and hence increasing the risk of serious side effects. Considering theses difficulties, the encapsulation of antifungal agents in nanoparticulate carriers has been used with the objective of modifying the pharmacokinetic of drugs resulting in more efficient treatments with less side effects. The purpose of this work was the preparation, characterization and the investigation of the release profiles of radiolabeled fluconazole nanocapsules. The size, homogeneity and zeta potential of NC preparations were determined with a Zetasizer 3000HS. The morphology and the structural organization were evaluated by atomic force microscopy (AFM). The release study in vitro of NC was evaluated in physiologic solution with or without 70% mouse plasma. The labeling yield of fluconazole with 99mTc was 94% and the radiolabeled drug was stable within 24h period. The encapsulation percentage of 99mTc-fluconazole in PLA-POLOX NC and PLA-PEG NC was approximately of 30%. The average diameter calculated by photon correlation spectroscopy (PCS) varied from 236 to 356 nm, while the average diameter determined by AFM varied from 238 to 411 nm. The diameter/height relation decreased significantly when 25% glutaraldehyde was used for NC fixation on mica. The zeta potential varied from -55 to -69 nm and surface-modified NC showed lower absolute values than conventional NC. The in vitro release of 99mTc-fluconazole in plasma medium of the conventional and surface-modified NC was greater than in saline. The drug release in plasma medium from conventional NC was faster than for surface-modified NC. The results obtained in this work suggest that the nanocapsules containing fluconazole could be used to identify infectious foci, due to the properties, such as size, zeta potential and controlled release of (99m)Tc-fluconazole. The surface-modified nanocapsules could constitute a long-circulating intravenous formulation of fluconazole for treating sepsis caused by disseminated form of candidiasis. However, in vivo studies should be considered and are under investigation.
几类抗真菌药物已用于念珠菌病的治疗，但晚期免疫缺陷患者在治疗后可能会出现不尽人意的结果。在这些情况下，有时会使用高剂量药物或多种药物联合使用，从而增加了严重副作用的风险。考虑到这些困难，将抗真菌剂封装在纳米颗粒载体中已被用于改变药物的药代动力学，从而实现更有效的治疗且副作用更少。本研究的目的是制备、表征放射性标记的氟康唑纳米胶囊并研究其释放曲线。使用Zetasizer 3000HS测定纳米胶囊制剂的大小、均匀性和zeta电位。通过原子力显微镜（AFM）评估形态和结构组织。在含有或不含有70%小鼠血浆的生理溶液中评估纳米胶囊的体外释放。99mTc标记氟康唑的标记产率为94%，且放射性标记药物在24小时内稳定。99mTc-氟康唑在PLA-POLOX纳米胶囊和PLA-PEG纳米胶囊中的包封率约为30%。通过光子相关光谱法（PCS）计算的平均直径在236至356nm之间变化，而通过AFM测定的平均直径在238至411nm之间变化。当使用25%戊二醛将纳米胶囊固定在云母上时，直径/高度比显著降低。zeta电位在-55至-69nm之间变化，表面改性的纳米胶囊显示出比传统纳米胶囊更低的绝对值。在血浆介质中，传统纳米胶囊和表面改性纳米胶囊的99mTc-氟康唑体外释放均大于在盐水中的释放。传统纳米胶囊在血浆介质中的药物释放比表面改性纳米胶囊更快。本研究获得的结果表明，由于（99m）Tc-氟康唑的大小、zeta电位和控释等特性，含氟康唑的纳米胶囊可用于识别感染灶。表面改性的纳米胶囊可构成一种长效循环的静脉注射用氟康唑制剂，用于治疗播散性念珠菌病引起的败血症。然而，应考虑进行体内研究，且相关研究正在进行中。
