Bioinspired Titanium Drug Eluting Platforms Based on a Poly-β-cyclodextrin-Chitosan Layer-by-Layer Self-Assembly Targeting Infections
Bioinspired Titanium Drug Eluting Platforms Based on a Poly-β-cyclodextrin-Chitosan Layer-by-Layer Self-Assembly Targeting Infections
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DOI：
10.1021/acsami.5b02402
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发表时间：
2015-06-17
影响因子：
9.5
通讯作者：
Lyskawa, Joel
中科院分区：
文献类型：
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作者：
Perez-Anes, Alexandra;Gargouri, Myriem;Lyskawa, Joel
在植入式钛基生物材料领域，感染和炎症是术后并发症最常见的形式。通过聚电解质多层（PEM）从植入物控制局部治疗药物输送最近已成为一种多功能技术，在将传统医疗植入物转变为药物输送系统方面显示出巨大的前景。在此，我们报告了基于针对感染的聚电解质多层生物活性涂层的新型可生物降解多药洗脱钛平台的设计和阐述。这些系统是在温和的条件下按照逐层 (L-b-L) 组装方式构建的，并包含通过静电相互作用结合在一起的两种生物相容性多糖。一种合成的、带负电的 β-环糊精基聚合物 (PCD) 因与疏水性治疗剂形成稳定且可逆的复合物而闻名，被用作多药储库，而壳聚糖 (CHT) 是一种天然存在的带正电的聚电解质，被用作控制药物输送速率的屏障。这些聚电解质多层膜通过仿生聚多巴胺 (PDA) 膜牢固地附着在钛表面上，该膜充当第一层粘合剂，促进 PEM 牢固锚定在生物材料上。在多层膜沉积之前，通过表面等离子体共振（SPR）监测两种带相反电荷的聚电解质之间的相互作用以及多层生长。使用浸涂策略设计了几种集成 5、10 和 15 个双层的 PEM，并通过比色滴定和重力分析估算了聚电解质表面密度。通过扫描电子显微镜（SEM）研究了这些多层系统的形态及其在生理介质中自然发生的降解，并通过轮廓测量和椭圆光度研究测量了它们的厚度。最后，涂层钛多层装置作为药物洗脱系统和治疗感染的能力得到了庆大霉素的验证，庆大霉素是一种由于其广泛的杀菌谱而在医学上常用的相关水溶性抗生素。
In the field of implantable titanium-based biomaterials, infections and inflammations are the most common forms of postoperative complications. The controlled local delivery of therapeutics from implants through polyelectrolyte multilayers (PEMs) has recently emerged as a versatile technique that has shown great promise in the transformation of a classical medical implant into a drug delivery system. Herein, we report the design and the elaboration of new biodegradable multidrug-eluting titanium platforms based on a polyelectrolyte multilayer bioactive coating that target infections. These systems were built up in mild conditions according to the layer-by-layer (L-b-L) assembly and incorporate two biocompatible polysaccharides held together through electrostatic interactions. A synthetic, negatively charged beta-cyclodextrin-based polymer (PCD), well-known for forming stable and reversible complexes with hydrophobic therapeutic agents, was exploited as a multidrug reservoir, and chitosan (CHT), a naturally occurring, positively charged polyelectrolyte, was used as a barrier for controlling the drug delivery rate. These polyelectrolyte multilayer films were strongly attached to the titanium surface through a bioinspired polydopamine (PDA) film acting as an adhesive first layer and promoting the robust anchorage of PEMs onto the biomaterials. Prior to the multilayer film deposition, the interactions between both oppositely charged polyelectrolytes, as well the multilayer growth, were monitored by employing surface plasmon resonance (SPR). Several PEMs integrating 5, 10, and 15 bilayers were engineered using the dip coating strategy, and the polyelectrolyte surface densities were estimated by colorimetric titrations and gravirnetric analyses. The morphologies of these multilayer systems, as well as their naturally occurring degradation in a physiological medium, were investigated by scanning electron microscopy (SEM), and their thicknesses were measured by means of profilometry and ellipsometry studies. Finally, the ability of the coated titanium multilayer devices to act as a drug-eluting system and to treat infections was validated with gentamicin, a relevant water-soluble antibiotic commonly used in medicine due to its broad bactericidal spectrum.