Ultrathin antibiotic walled microcapsules
Ultrathin antibiotic walled microcapsules
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DOI：
10.1021/bm049554a
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发表时间：
2005-01-01
影响因子：
6.2
通讯作者：
Hartmann, J
中科院分区：
文献类型：
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作者：
Khopade, AJ;Arulsudar, N;Hartmann, J
采用层层自组装技术将聚电解质（PE）/聚阳离子氨基糖苷（AmG）多层膜沉积在氧化锌（ZnO）胶体颗粒上，然后溶解ZnO模板核，制备了由阴离子聚电解质（PE）和聚阳离子氨基糖苷（AmG）抗生素药物组成的超薄微胶囊。聚电解质，葡聚糖硫酸钠（DxS）和聚（苯乙烯磺酸）（PSS），由于它们的不同的主链结构被选择。氨基糖苷类抗生素硫酸妥布霉素（TbS）被用于研究DxS/TbS或PSS/TbS多层膜。ZnO芯上的多层生长的特征在于交替zeta电位值是不同的DxS/TbS和PSS/TbS多层膜由于PE化学和其与Zn 2+离子的相互作用。透射和扫描电子显微镜提供证据的PE/TbS多层涂层的ZnO核心颗粒。需要使用弱有机酸缓慢酸分解ZnO核和在分散体中存在足够量的Zn 2+以产生抗生素多层胶囊。两种类型胶囊的形态特征没有差异;尽管[PSS/TbS]（5）胶囊的产率显著高于[DxS/TbS]（5）胶囊，这与形成胶囊壁的DxS/TbS/Zn 2+和PSS/TbS/Zn 2+复合物的理化性质有关。使用石英晶体微量天平和高效液相色谱技术，这表明更少的TbS负载在两个，胶囊和平面的金基板上的多层膜中的ThS量确定，比理论的DxS：TbS或PSS：TbS的化学计量比。[PE/TbS]（6）多层膜在生理缓冲液中的分解最快，其次是甘露醇和水。[PSS/TbS]（6）多层膜的分解速率比[DxS/TbS]（6）单层膜慢。DxS/TbS在盐水条件下的不完全分解表明氢键对DxS/TbS多层膜的稳定性起主要作用。PSS中苯环间的氢键和疏水相互作用的结合是PSS/TbS多层膜稳定性的原因。兔体内研究突出了PE/AmG微囊的安全性和持续给药潜力。本文介绍的抗生素壁微胶囊适用于持续眼用抗生素给药。
Ultrathin microcapsules comprised of anionic polyelectrolytes (PE) and a polycationic aminoglycoside (AmG) antibiotic drug were prepared by depositing PE/AmG multilayers on zinc oxide (ZnO) colloid particles using the layer-by-layer self-assembly technique and subsequently dissolving the ZnO templated cores. The polyelectrolytes, dextran sulfate sodium (DxS) and poly(styrenesulfonate) (PSS), were selected owing to their different backbone structure. An aminoglycoside, tobramycin sulfate (TbS), was used for studying DxS/TbS or PSS/TbS multilayer films. The multilayer growth on ZnO cores was characterized by alternating zeta potential values that were different for the DxS/TbS and PSS/TbS multilayers due to the PE chemistry and its interaction with Zn2+ ions. Transmission and scanning electron microscopy provide evidence of PE/TbS multilayer coating on ZnO core particles. The slow acid-decomposition of the ZnO cores using weak organic acids and the presence of sufficient quantity of Zn2+ in the dispersion were required to produce antibiotic multilayer capsules. There was no difference in the morphological characteristics of the two types of capsules; although, the yield for [PSS/TbS](5) capsules was significantly higher than for [DxS/TbS](5) capsules which was related to the physicochemical properties of DxS/TbS/Zn2+ and PSS/TbS/Zn2+ complexes forming the capsule wall. The ThS quantity in the multilayer films was determined using a quartz crystal microbalance and high performance liquid chromatography techniques which showed less TbS loading in both, capsules and multilayers on planar gold substrate, than the theoretical DxS:TbS or PSS:TbS stoichiometric ratio. The decomposition of the [PE/TbS](6) multilayers was fastest in physiological buffer followed by mannitol and water. The decomposition rate of the [PSS/TbS](6) multilayers was slower than [DxS/TbS](6) monolayers. The incomplete decomposition of DxS/TbS under saline conditions suggests the major role of hydrogen bonding for stability of DxS/TbS multilayers. A combination of hydrogen bonding and hydrophobic interaction between phenyl rings in PSS was responsible for PSS/TbS multilayer stability. In vivo studies in rabbits highlight the safety and sustained drug delivery potential of the PE/AmG microcapsules. The antibiotic walled ultrathin capsules presented here are suitable for sustained ophthalmic antibiotic delivery.