Polara Himanshu, Shah Tejas, Babanyinah Godwin, Wang Hanghang, Bhadran Abhi, Biewer Michael C, Stefan Mihaela C
Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States.
Biomacromolecules. 2025 May 12;26(5):3213-3223. doi: 10.1021/acs.biomac.5c00280. Epub 2025 Apr 30.
Polymeric micelles are effective for drug delivery but often face instability, low drug loading capacity (DLC), and premature drug leakage. Herein, we report that disubstituted γ-amide functionalized ε-caprolactone (ε-CL) monomers double the substituent density per polymeric unit, enhancing micelle properties and improving drug delivery applications. Three hydrophobic ε-CL monomers with two propyl groups, two benzyl groups, and a combination of propyl and benzyl groups were synthesized. The obtained monomers were polymerized by ring-opening polymerization using poly(ethylene glycol) (PEG) as a macroinitiator and the hydrophilic block. The synthesized copolymers successfully self-assembled to form micelles, and doxorubicin (DOX) was loaded into all micelles. Poly(ethylene glycol)poly(-propyl--benzyl-7-oxopane-4-carboxamide) (PEGPBnPyCL) exhibited 7.33 wt % DLC with pH-responsive drug release in acidic conditions. In addition, the DOX-loaded micelles of PEG--PBnPyCL exhibited nearly 20% cell viability in MDA-MB-231 cancer cells. These results contribute to advancing polymeric micelles as drug carriers with clinical translation potential.
聚合物胶束对药物递送有效，但常常面临稳定性差、药物负载量（DLC）低和药物过早泄漏等问题。在此，我们报告二取代的γ-酰胺官能化ε-己内酯（ε-CL）单体使每个聚合物单元的取代基密度加倍，增强了胶束性能并改善了药物递送应用。合成了三种具有两个丙基、两个苄基以及丙基和苄基组合的疏水性ε-CL单体。使用聚乙二醇（PEG）作为大分子引发剂和亲水嵌段，通过开环聚合将所得单体进行聚合。合成的共聚物成功自组装形成胶束，并将阿霉素（DOX）负载到所有胶束中。聚（乙二醇）聚（-丙基--苄基-7-氧杂环庚烷-4-甲酰胺）（PEGPBnPyCL）表现出7.33 wt%的DLC，在酸性条件下具有pH响应性药物释放。此外，负载DOX的PEG--PBnPyCL胶束在MDA-MB-231癌细胞中表现出近20%的细胞活力。这些结果有助于推动聚合物胶束作为具有临床转化潜力的药物载体的发展。
