Meier Nils, Berten-Schunk Leonie, Roger Yvonne, Hänsch Robert, Hoffmann Andrea, Bunjes Heike, Dempwolf Wibke, Menzel Henning
Institute for Technical Chemistry, Macromolecular Chemistry, TU Braunschweig, Hagenring 30, 38106, Braunschweig, Germany.
Institute of Pharmaceutical Technology and Biopharmaceutics, TU Braunschweig, Mendelssohnstrasse 1, 38106, Braunschweig, Germany.
Macromol Biosci. 2025 Apr;25(4):e2400447. doi: 10.1002/mabi.202400447. Epub 2025 Jan 13.
Implant-integrated drug delivery systems that enable the release of biologically active factors can be part of an in situ tissue engineering approach to restore biological function. Implants can be functionalized with drug-loaded nanoparticles through a layer-by-layer assembly. Such coatings can release biologically active levels of growth factors. Sustained release is desired for many in vivo applications. The layer-by-layer technique also allows for the addition of extra layers, which can serve as "barriers" to delay the release. Electrospun Polycaprolactone (PCL) fiber mats are modified with a Chitosan (CS) grafted with PCL sidechains (CS-g-PCL) and coated with transforming growth factor beta 3 (TGF-β) loaded Chitosan/tripolyphosphate nanoparticles as a drug delivery system. Additional layers including polystyrene sulfonate, alginate, carboxymethyl cellulose, and liposomes (phosphatidylcholine) are applied. Streaming potential and X-ray photoelectron spectroscopy (XPS) measurements indicated a strong interpenetration of the chitosan and polyanion layers, while liposomes formed separate layers, which are more promising for sustained release. All samples release TGF-β at different cumulative levels without altering release kinetics. Variations in layer structure, interpenetration, and stability depending on the chitosan used are observed, which ultimately has minimal impact on the release kinetics. Polyelectrolyte layers strongly interpenetrated the active layers and therefore do not act as effective diffusion barriers, while the liposome layer, though separated, lacked sufficient stability.
能够释放生物活性因子的植入物集成药物递送系统可以成为原位组织工程方法的一部分,以恢复生物功能。通过层层组装,可以用载药纳米颗粒对植入物进行功能化处理。这种涂层可以释放生物活性水平的生长因子。许多体内应用都需要持续释放。层层技术还允许添加额外的层,这些层可以作为“屏障”来延迟释放。用接枝有聚己内酯(PCL)侧链的壳聚糖(CS)(CS-g-PCL)对静电纺丝聚己内酯(PCL)纤维垫进行改性,并涂覆负载转化生长因子β3(TGF-β)的壳聚糖/三聚磷酸钠纳米颗粒作为药物递送系统。应用了包括聚苯乙烯磺酸盐、藻酸盐、羧甲基纤维素和脂质体(磷脂酰胆碱)在内的额外层。流动电位和X射线光电子能谱(XPS)测量表明壳聚糖层和聚阴离子层强烈相互渗透,而脂质体形成了单独的层,这对于持续释放更有前景。所有样品均以不同的累积水平释放TGF-β,而不改变释放动力学。观察到取决于所用壳聚糖的层结构、相互渗透和稳定性的变化,这最终对释放动力学的影响最小。聚电解质层强烈渗透到活性层中,因此不能作为有效的扩散屏障,而脂质体层虽然是分离的,但缺乏足够的稳定性。