Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany.
Electron Microscopy Facility, Institute of Pathology, RWTH University Hospital, 52074 Aachen, Germany.
Biomacromolecules. 2023 Oct 9;24(10):4444-4453. doi: 10.1021/acs.biomac.2c01261. Epub 2023 Feb 8.
Polymeric micelles are among the most extensively used drug delivery systems. Key properties of micelles, such as size, size distribution, drug loading, and drug release kinetics, are crucial for proper therapeutic performance. Whether polymers from more controlled polymerization methods produce micelles with more favorable properties remains elusive. To address this question, we synthesized methoxy poly(ethylene glycol)--(-(2-benzoyloxypropyl)methacrylamide) (mPEG--p(HPMAm-Bz)) block copolymers of three different comparable molecular weights (∼9, 13, and 20 kDa), via both conventional free radical (FR) and reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were subsequently employed to prepare empty and paclitaxel-loaded micelles. While FR polymers had relatively high dispersities ( ∼ 1.5-1.7) compared to their RAFT counterparts ( ∼ 1.1-1.3), they formed micelles with similar pharmaceutical properties (e.g., size, size distribution, critical micelle concentration, cytotoxicity, and drug loading and retention). Our findings suggest that pharmaceutical properties of mPEG--p(HPMAm-Bz) micelles do not depend on the synthesis route of their constituent polymers.
聚合物胶束是应用最广泛的药物输送系统之一。胶束的关键性质，如粒径、粒径分布、载药量和药物释放动力学，对其治疗性能至关重要。通过更可控的聚合方法得到的聚合物是否能产生具有更优性质的胶束仍然难以捉摸。为了解决这个问题，我们通过传统的自由基（FR）和可逆加成-断裂链转移（RAFT）聚合，合成了三种不同分子量（约 9、13 和 20 kDa）的甲氧基聚（乙二醇）-（-（2-苯甲酰氧基丙基）甲基丙烯酰胺）（mPEG-p（HPMAm-Bz））嵌段共聚物。随后，这些聚合物被用于制备空和紫杉醇负载的胶束。虽然 FR 聚合物的分散度相对较高（约 1.5-1.7），与其 RAFT 对应物（约 1.1-1.3）相比，但它们形成的胶束具有相似的药物性质（例如粒径、粒径分布、临界胶束浓度、细胞毒性以及载药量和保留率）。我们的研究结果表明，mPEG-p（HPMAm-Bz）胶束的药物性质不取决于其组成聚合物的合成途径。
