两亲性核交联星形聚合物用于从疏水基质中传递出亲水药物《Biomacromolecules》

Amphiphilic Core Cross-Linked Star Polymers for the Delivery of Hydrophilic Drugs from Hydrophobic Matrices

Katarzyna Somszor, Stephanie Allison-Logan, Fatemeh Karimi, Thomas McKenzie, Qiang Fu, Andrea O’Connor, Greg Qiao*, and Daniel Heath*

Department of Biomedical Engineering, University of Melbourne, Parkville, 3010 VIC, Australia

Biomacromolecules 2021, 22, 6, 2554–2562

Publication Date: May 13, 2021

https://doi.org/10.1021/acs.biomac.1c00296

Abstract

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.

SUBJECTS:

• Drug delivery,

• Heparin,

• Hydrophilicity,

• Hydrophobicity,

• Star polymers