Perni Stefano, Prokopovich Polina
School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.
School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.
Nanomedicine. 2017 Feb;13(2):539-548. doi: 10.1016/j.nano.2016.10.001. Epub 2016 Oct 13.
The efficient delivery of therapeutic molecules to the cartilage of joints is a major obstacle in developing useful therapeutic interventions; hence, a targeted drug delivery system for this tissue is critical. We have overcome the challenge by developing a system that employs electrostatic attraction between the negatively charged constituents of cartilage and a positively charged polymer, poly-beta amino esters (PBAEs). We have demonstrated cartilage uptake of dexamethasone (DEX) covalently bound to the PBAE was doubled and retention in tissues prolonged compared to the equivalent dose of the commercial drug formulation. Moreover, no adverse effects on chondrocytes were found. Our data also show that PBAEs can bind not only healthy cartilage tissues but also enzymatically treated cartilage mimicking early stages of OA. Our PBAEs-prodrug technology's advantages are fourfold; the specificity and efficacy of its targeting mechanism for cartilage, the ease of its production and the low-cost nature of the delivery system.
将治疗性分子有效递送至关节软骨是开发有效治疗干预措施的主要障碍；因此，针对该组织的靶向药物递送系统至关重要。我们通过开发一种利用软骨带负电成分与带正电聚合物聚β-氨基酯（PBAEs）之间静电吸引的系统克服了这一挑战。我们已经证明，与同等剂量的市售药物制剂相比，与PBAE共价结合的地塞米松（DEX）在软骨中的摄取量增加了一倍，并且在组织中的保留时间延长。此外，未发现对软骨细胞有不良影响。我们的数据还表明，PBAEs不仅可以结合健康的软骨组织，还可以结合模拟骨关节炎早期阶段的经酶处理的软骨。我们的PBAEs前药技术具有四个优势；其对软骨靶向机制的特异性和有效性、生产的简易性以及递送系统的低成本特性。
