Vieira Débora B, Pacheco Luis F, Carmona-Ribeiro Ana M
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, CP 26077, Avenida Lineu Prestes 748, Butantã, CEP 05513-970, São Paulo, Brazil.
J Colloid Interface Sci. 2006 Jan 1;293(1):240-7. doi: 10.1016/j.jcis.2005.06.046. Epub 2005 Aug 10.
Our previous work has shown that dioctadecyldimethylammonium bromide (DODAB) bilayer fragments (BF) presented antimicrobial activity, solubilized fungicides, e.g., amphotericin B and miconazole (MCZ), stabilized hydrophobic drug particles and were effective in vivo. Here, the interaction between MCZ and DODAB BF is evaluated from determination of BF loading capacity and effects of drug-to-lipid molar proportion (MP) on particle size, zeta potential and gel-to-liquid-crystalline phase transition T(m). DODAB BF solubilized MCZ over a range of MP. BF loading capacity was 0.5 mM MCZ at 5 mM DODAB. Above this limit, the drug aggregated in the dispersion. At pH 6.3, BF zeta potentials decreased with MP, suggesting insertion of deprotonated drug into the bilayer. MCZ optical spectra in BF were similar to those in best organic solvent, confirming drug solubilization. At MP 1:10, BF T(m) remained unchanged, suggesting drug capture at BF hydrophobic edges. At MP 1:10, T(m) decreased, showing MCZ insertion into DODAB bilayer. However, drug was expelled from the bilayer core upon lowering temperature. Minimal fungicidal concentrations against C. albicans were synergically reduced by 10 times for drug/BF.
我们之前的工作表明，二辛基二甲基溴化铵（DODAB）双层碎片（BF）具有抗菌活性，可溶解杀菌剂，如两性霉素B和咪康唑（MCZ），稳定疏水性药物颗粒，并且在体内有效。在此，通过测定BF载药量以及药物与脂质摩尔比（MP）对粒径、zeta电位和凝胶-液晶相变温度T(m)的影响，来评估MCZ与DODAB BF之间的相互作用。DODAB BF在一系列MP范围内可溶解MCZ。在5 mM DODAB时，BF载药量为0.5 mM MCZ。超过此限度，药物在分散体中聚集。在pH 6.3时，BF的zeta电位随MP降低，表明去质子化药物插入双层中。BF中MCZ的光谱与最佳有机溶剂中的光谱相似，证实了药物的溶解。在MP为1:10时，BF的T(m)保持不变，表明药物在BF疏水边缘捕获。在MP为1:10时，T(m)降低，表明MCZ插入DODAB双层中。然而，降低温度时药物从双层核心中被排出。药物/BF对白色念珠菌的最低杀菌浓度协同降低了10倍。
