Li Zi-Xian, Yang Chen, Guo Lei, Ling Jun, Xu Jun-Ting
State Key Laboratory of Biobased Transportation Fuel Technology, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310058, China.
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310058, China.
Molecules. 2025 Jul 24;30(15):3108. doi: 10.3390/molecules30153108.
Poly(ε-caprolactone)--polysarcosine (PCL--PSar) block copolymers (BCPs) emerge as a promising alternative to conventional poly(-caprolactone)--poly(ethylene oxide) BCPs for biomedical applications, leveraging superior biocompatibility and biodegradability. In this study, we synthesized two series of PCL--PSar BCPs with controlled polymerization degrees ( of PCL: 45/67; of PSar: 28-99) and low polydispersity indexes ( ≤ 1.1) and systematically investigated their crystallization-driven self-assembly (CDSA) in alcohol solvents (ethanol, -butanol, and -hexanol). It was found that the limited solubility of PSar in alcohols resulted in competition between micellization and crystallization during self-assembly of PCL--PSar, and thus coexistence of lamellae and spherical micelles. To overcome this morphological heterogeneity, we developed a modified self-seeding method by employing a two-step crystallization strategy (i.e., = 33 °C and = 8 °C), achieving conversion of micelles into crystals and yielding uniform self-assembled structures. PCL--PSar BCPs with short PSar blocks tended to form well-defined two-dimensional lamellar crystals, while those with long PSar blocks induced formation of hierarchical structures in the PCL series and polymer aggregation on crystal surfaces in the PCL series. Solvent quality notably influenced the self-assembly pathways of PCL--PSar. Lamellar crystals were formed in ethanol and -butanol, but micrometer-scale dendritic aggregates were generated in -hexanol, primarily due to a significant Hansen solubility parameter mismatch. This study elucidated the CDSA mechanism of PCL--PSar in alcohols, enabling precise structural control for biomedical applications.
聚（ε-己内酯）-聚肌氨酸（PCL-PSar）嵌段共聚物（BCPs）凭借其卓越的生物相容性和生物降解性，成为生物医学应用中传统聚（-己内酯）-聚（环氧乙烷）BCPs的一种有前景的替代品。在本研究中，我们合成了两个系列的PCL-PSar BCPs，其聚合度可控（PCL的聚合度为45/67；PSar的聚合度为28 - 99）且多分散指数较低（≤1.1），并系统研究了它们在醇类溶剂（乙醇、正丁醇和正己醇）中的结晶驱动自组装（CDSA）。研究发现，PSar在醇类中的有限溶解度导致PCL-PSar自组装过程中胶束化和结晶之间存在竞争，从而使片层和球形胶束共存。为克服这种形态异质性，我们采用两步结晶策略（即33°C和8°C）开发了一种改进的自晶种法，实现了胶束向晶体的转变并产生均匀的自组装结构。具有短PSar嵌段的PCL-PSar BCPs倾向于形成定义明确的二维片层晶体，而具有长PSar嵌段的则在PCL系列中诱导形成分级结构，在PCL系列中导致晶体表面的聚合物聚集。溶剂性质显著影响PCL-PSar的自组装途径。在乙醇和正丁醇中形成了片层晶体，但在正己醇中产生了微米级树枝状聚集体，这主要是由于显著的汉森溶解度参数不匹配。本研究阐明了PCL-PSar在醇类中的CDSA机制，为生物医学应用实现了精确的结构控制。
