Department of Biomedical Engineering, University of Melbourne, Parkville, 3010 VIC, Australia.
Department of Chemical Engineering, University of Melbourne, Parkville, 3010 VIC, Australia.
Biomacromolecules. 2021 Jun 14;22(6):2554-2562. doi: 10.1021/acs.biomac.1c00296. Epub 2021 May 13.
The delivery of hydrophilic drugs from hydrophobic polymers is a long-standing challenge in the biomaterials field due to the limited solubility of the therapeutic agent within the polymer matrix. In this work, we develop a drug delivery mechanism that enables the impregnation and subsequent elution of hydrophilic drugs from a hydrophobic polymer material. This was achieved by synthesizing core cross-linked star polymer amphiphiles with hydrophilic cores and hydrophobic coronas. While significant work has been done to create nanocarriers for hydrophilic drugs, this work is distinct from previous work in that it designs amphiphilic and core cross-linked particles for controlled release from hydrophobic matrices. Ultraviolet-mediated atom transfer radical polymerization was used to synthesize the poly(ethylene glycol) (PEG)-based hydrophilic cores of the star polymers, and hydrophobic coronas of poly(caprolactone) (PCL) were then built onto the stars using ring-opening polymerization. We illustrated the cytocompatibility of PCL loaded with these star polymers through human endothelial cell adhesion and proliferation for up to 7 days, with star loadings of up to 40 wt %. We demonstrated successful loading of the hydrophilic drug heparin into the star polymer core, achieving a loading efficiency and content of 50 and 5%, respectively. Finally, the heparin-loaded star polymers were incorporated into a PCL matrix and sustained release of heparin was illustrated for over 40 days. These results support the use of core cross-linked star polymer amphiphiles for the delivery of hydrophilic drugs from hydrophobic polymer matrices. These materials were developed for application as drug-eluting and biodegradable coronary artery stents, but this flexible drug delivery platform could have impact in a broad range of medical applications.
亲水药物从疏水性聚合物中递送是生物材料领域中的一个长期挑战，这是由于治疗剂在聚合物基质中的溶解度有限。在这项工作中，我们开发了一种药物递送机制，能够将亲水性药物从疏水性聚合物材料中浸渍和随后洗脱。这是通过合成具有亲水核和疏水壳的核交联星形聚合物两亲物来实现的。虽然已经做了大量工作来创建亲水性药物的纳米载体，但这项工作与以前的工作不同，它设计了两亲性和核交联颗粒，用于从疏水性基质中控制释放。使用紫外介导的原子转移自由基聚合来合成星形聚合物的基于聚乙二醇（PEG）的亲水核，然后使用开环聚合将疏水性聚己内酯（PCL）壳构建到星形物上。我们通过人类内皮细胞粘附和增殖实验表明了负载这些星形聚合物的 PCL 的细胞相容性，最高可达 40wt%的星形负载。我们成功地将亲水性药物肝素载入星形聚合物核中，分别实现了 50%和 5%的载药效率和载药量。最后，将负载肝素的星形聚合物掺入 PCL 基质中，并说明了肝素的持续释放超过 40 天。这些结果支持使用核交联星形聚合物两亲物从疏水性聚合物基质中递送亲水性药物。这些材料是为应用于药物洗脱和可生物降解的冠状动脉支架而开发的，但这种灵活的药物输送平台可能会在广泛的医疗应用中产生影响。
