Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina.
Instituto de Desarrollo Tecnológico para la Industria Química (INTEC), CONICET, Colectora Ruta Nac. N° 168, km. 0, Pje. El Pozo, 3000 Santa Fe, Argentina.
Mater Sci Eng C Mater Biol Appl. 2016 Dec 1;69:236-46. doi: 10.1016/j.msec.2016.06.071. Epub 2016 Jun 23.
The development and characterization of a novel, gel-type material based on a dendronized polymer (DP) loaded with ciprofloxacin (CIP), and the evaluation of its possible use for controlled drug release, are presented in this work. DP showed biocompatible and non-toxic behaviors in cultured cells, both of which are considered optimal properties for the design of a final material for biomedical applications. These results were encouraging for the use of the polymer loaded with CIP (as a drug model), under gel form, in the development of a new controlled-release system to be evaluated for topical administration. First, DP-CIP ionic complexes were obtained by an acid-base reaction using the high density of carboxylic acid groups of the DP and the amine groups of the CIP. The complexes obtained in the solid state were broadly characterized using FTIR spectroscopy, XRP diffraction, DSC-TG analysis and optical microscopy techniques. Gels based on the DP-CIP complexes were easily prepared and presented excellent mechanical behaviors. In addition, optimal properties for application on mucosal membranes and skin were achieved due to their high biocompatibility and acute skin non-irritation. Slow and sustained release of CIP toward simulated physiological fluids was observed in the assays (in vitro), attributed to ion exchange phenomenon and to the drug reservoir effect. An in vitro bacterial growth inhibition assay showed significant CIP activity, corresponding to 38 and 58% of that exhibited by a CIP hydrochloride solution at similar CIP concentrations, against Staphylococcus aureus and Pseudomonas aeruginosa, respectively. However, CIP delivery was appropriate, both in terms of magnitude and velocity to allow for a bactericidal effect. In conclusion, the final product showed promising behavior, which could be exploited for the treatment of topical and mucosal opportunistic infections in human or veterinary applications.
本工作提出了一种基于树枝状聚合物（DP）负载环丙沙星（CIP）的新型凝胶型材料的开发和特性研究，并评估了其在控制药物释放方面的潜在用途。DP 在培养细胞中表现出良好的生物相容性和无毒特性，这是设计用于生物医学应用的最终材料的理想特性。这些结果为使用负载 CIP 的聚合物（作为药物模型）以凝胶形式开发新的控释系统用于局部给药提供了令人鼓舞的结果。首先，通过 DP 中的高密度羧酸基团与 CIP 的胺基之间的酸碱反应获得 DP-CIP 离子复合物。通过 FTIR 光谱、XRP 衍射、DSC-TG 分析和光学显微镜技术对固态下获得的复合物进行了广泛的表征。基于 DP-CIP 复合物的凝胶很容易制备，并表现出优异的机械性能。此外，由于其高生物相容性和急性皮肤无刺激性，获得了适用于粘膜和皮肤的最佳性能。在模拟生理液中的体外释放实验中观察到 CIP 的缓慢和持续释放，这归因于离子交换现象和药物储库效应。体外细菌生长抑制实验表明，CIP 具有显著的活性，在类似 CIP 浓度下，对金黄色葡萄球菌和铜绿假单胞菌的活性分别为盐酸环丙沙星溶液的 38%和 58%。然而，CIP 的释放量和释放速度适中，足以发挥杀菌作用。总之，最终产品表现出有前途的行为，可用于治疗人类或兽医应用中的局部和粘膜机会性感染。
