基于超疏水表面构建骨科疾病用药物传输系统的研究

Recently, it becomes a hot topic to construct drug delivery systems for the prevention and treatment of orthopedic diseases, and high drug encapsulation efficiency along with controlled drug release are the keys for reaching the optimal therapeutic effect of these systems. Inspired by the anti-adhesive property of the lotus leaf, a novel preparation method based on the superhydrophobic surface is proposed to achieve the goals mentioned above. In this bio-inspired method, after the droplet of bone cement slurry containing drug dripped onto the superhydrophobic surface, the self setting behavior of bone cement makes the drug-loaded particles formed, and the anti-adhesive property of the superhydrophobic surface makes the drug encapsulated efficiently; then, by coating the drug-loaded bone cement particle with polymer layer the drug controlled release can be easily achieved. In this project, the controllable fabrication of polymer/drug-loaded bone cement composite particles with different composition and structure is systematically investigated, then the drug encapsulation and release behavior and the corresponding mechanism are studied, and the effective ways to achieve high drug encapsulation efficiency and controlled release are further explored; on this basis, the anticancer drug delivery system with high drug encapsulation efficiency and sustained drug release profile is constructed to explore its application in prevention of bone tumor recurrence. This project will provide a novel approach to fabricate drug delivery systems for the treatment of orthopedic diseases.

构建药物传输系统来预防和治疗骨科疾病是目前的研究热点，药物高效包封和缓控释放是这类输运体系高效发挥作用的关键。项目申请人从自然界荷叶表面抗粘附的现象获得灵感，拟建立一种新颖的药物传输系统制备方法来实现上述目标。在这种生物灵感新方法中，将含药骨水泥滴于仿荷叶结构的超疏水表面，骨水泥自固化的特性会使得载药颗粒固化成型，同时超疏水表面的抗粘附性会使药物被高效包封；进一步通过对载药骨水泥颗粒进行高分子包覆来实现药物的缓控释放。本项目将利用上述新方法制备组成和结构可控的高分子/载药骨水泥复合颗粒，探索药物包封和释放的规律和机理，寻求药物高效包封和缓控释放的有效途径；在此基础上，构建具有抗癌药高效包封以及缓释特性的高分子/载抗癌药骨水泥复合颗粒，探究其在预防术后骨肿瘤复发方面的应用。本项目将为骨科疾病用药物传输系统的制备提供一种新方法。

构建药物传输系统来预防和治疗疾病是目前的研究热点，药物高效包封和缓控释放是这类输运体系高效发挥作用的关键。项目申请人从自然界的特殊浸润性（荷叶、玫瑰花瓣）获得灵感，发展了基于超疏水表面（超疏水低粘附、高粘附表面）构建颗粒的新方法，成功制备了组成可调（高分子材料、无机材料、复合材料）、结构可控（单一结构、多隔室结构）的颗粒材料，实现了单一药物（亲水、疏水）以及多种药物同时高包封率负载以及缓控释放，阐明了药物高效包封和可控释放的机理。主要开展了以下三部分工作：（1）基于超疏水低粘附表面制备载药硫酸钙骨水泥颗粒的研究。采用静电喷射技术成功制备超疏水低粘附基底；进一步利用该基底作为制备平台，构建出尺寸可控的硫酸钙骨水泥颗粒，明确了颗粒的形成机理，探究了其对水溶性药物对乙酰氨基酚和水难溶性药物布洛芬的包封及释放能力。结果表明，颗粒对两种药物的包封率高达91%以上，且释放速率可以通过颗粒粒径及药物复合量进行调控。（2）基于仿生超疏水低粘附表面构建海藻酸钙载药颗粒的研究。探究了超疏水表面介导的海藻酸钙载药颗粒的制备，研究了颗粒形成的条件及机理，发现了药物对乙酰氨基酚的包封率高达88%以上，且药物呈现出pH响应性释放，明晰了药物高效包封和可控释放的机理。（3）基于超疏水高粘附表面制备两亲性多隔室颗粒的研究。利用电纺丝技术制备了超疏水高粘附表面，基于这类特殊表面对水强的粘附力的特点，将水凝胶颗粒与超疏水纤维基底有效组装形成两亲性颗粒，进一步采取多次组装的方式，制备得到双亲性隔室可控的颗粒，探究其对于两种不同种类药物的包裹以及可控释放能力。明确了两亲性多隔室颗粒的形成机理、药物程序式释放以及按需释放的机制。本项目基于超疏水表面制备颗粒的新策略，有望为药物传输系统的构建、多细胞共培养等生物医用领域提供理论指导和数据支持。