Leibniz-Institut fur Polymerforschung Dresden e.V., Abteilung Polyelektrolyte und Dispersionen, Hohe Straße 6, D-01069 Dresden, Germany.
Technische Universität Dresden, Fachrichtung für Chemie und Lebensmittelchemie, D-01062 Dresden, Germany.
Curr Pharm Des. 2018;24(13):1341-1348. doi: 10.2174/1381612824666171213095523.
In this contribution an overview is given on own work concerning drug loaded Polyelectrolyte Complex (PEC) Nanoparticles (NP) used to functionalize Bone Substitute Materials (BSM) for the therapy of bone defects associated with systemic bone diseases. In this context, drug loaded PEC NP have certain advantages, which are exemplarily summarized herein.
Concerning preparative methods PEC NP were fabricated by controlled mixing of polycation and polyanion solutions and integration of charged drugs during and after mixing. Control was taken on the stoichiometric ratio related to cationic and anionic repeating units, which was chosen close to zero for the final applied PEC NP. Concerning analytical methods a couple of physical-chemical methods were applied like colloid titration, Dynamic Light Scattering (DLS), Scanning Force Microscopy (SFM), Fourier Transform infrared (FTIR) spectroscopy, Ultraviolet-Visible (UV-VIS) and Circular Dichroism (CD) spectroscopy to characterize colloid stability, adhesiveness, drug loading and release of PEC NP. Moreover, standard biochemical and microbiological assays were applied.
Drug loaded PEC NP consist of oppositely charged biorelated Polyelectrolytes (PEL) like ionic polysaccharides or ionic polypeptides and also synthetic PEL, which are mixed and processed in aqueous media. At first, freshly prepared drug/PEC NP exhibit time dependent colloidal stability in the range of weeks and months, which enables and simplifies storage, transport and application in the medical field. Secondly, after deposition and drying of drug/PEC NP a local wet adhesive PEC matrix at the BSM remains in contact to relevant aqueous media (e.g. buffer, cell culture medium), which minimizes asepsis, systemic toxicity, immune or inflammatory reaction. Thirdly, cell compatible PEC NP coatings were identified, which showed only minimal effects on various relevant bone related cells due to biorelateness, complexation, local confinement and low surface area. Fourthly, PEC NP elute drugs for bone healing like bisphosphonates, antibiotics and growth factors (e.g. bone morphogenetic proteins) in delayed and sustained manner. Moreover, the onset of elution could be triggered by thermoresponsive PEL via temperature increase giving clinicians a tool into hand allowing spatiotemporal drug release on demand. Finally, drug/PEC NP could be integrated into commercial or still developed allotropic stabilizing or defect filling BSM systems.
在本研究中，作者综述了载药聚电解质复合物（PEC）纳米颗粒（NP）在用于治疗与全身骨病相关的骨缺损的骨替代材料（BSM）功能化方面的研究工作。在此背景下，载药 PEC NP 具有某些优势，本文对此进行了简要总结。
关于制备方法，PEC NP 通过控制聚阳离子和聚阴离子溶液的混合以及在混合过程中和混合后整合带电荷的药物来制备。通过控制与阳离子和阴离子重复单元相关的化学计量比来控制，该化学计量比选择接近于零，以获得最终应用的 PEC NP。关于分析方法，应用了几种物理化学方法，如胶体质点滴定、动态光散射（DLS）、扫描力显微镜（SFM）、傅里叶变换红外（FTIR）光谱、紫外-可见（UV-VIS）和圆二色性（CD）光谱来表征 PEC NP 的胶体稳定性、粘附性、载药量和释放。此外，还应用了标准的生化和微生物学检测方法。
载药 PEC NP 由相反电荷的生物相关聚电解质（PEL）组成，如离子多糖或离子多肽，以及合成 PEL，这些 PEL 在水介质中混合和处理。首先，新制备的载药/PEC NP 在数周至数月的时间内表现出时间依赖性胶体稳定性，这使得载药/PEC NP 的储存、运输和在医学领域的应用变得简单。其次，载药/PEC NP 沉积和干燥后，BSM 中仍保留局部湿润的 PEC 基质与相关水性介质（如缓冲液、细胞培养基）接触，最大限度地减少了无菌性、全身毒性、免疫或炎症反应。第三，鉴定了细胞相容的 PEC NP 涂层，由于生物相关性、络合、局部限制和低表面积，这些 PEC NP 涂层对各种相关的骨相关细胞仅表现出最小的影响。第四，PEC NP 以延迟和持续的方式洗脱用于骨愈合的药物，如双膦酸盐、抗生素和生长因子（如骨形态发生蛋白）。此外，通过增加温度，可以通过热响应性 PEL 触发洗脱的开始，为临床医生提供一种按需控制时空药物释放的工具。最后，载药/PEC NP 可整合到商业或仍在开发的各向异性稳定或缺陷填充 BSM 系统中。
