Improving drug release performance of phosphazene-based crosslinked polyprodrug nanoparticles for tumor chemotherapy by enhancing hydrophilicity with polyethylene glycol

IF 6.3 2区化学 Q1 POLYMER SCIENCE

European Polymer Journal Pub Date : 2025-08-04 DOI:10.1016/j.eurpolymj.2025.114196

Ziqian Gao, Peng Liu

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引用次数: 0

Abstract

Phosphazene-based crosslinked polyprodrug nanoparticles have attracted more interests as nano-scaled drug delivery systems (nano-DDSs) in tumor chemotherapy owing to easy synthesis and sensitive pH-triggered degradation. However, their practical application is restricted by their poor dispersibility and slow drug release, due to the inherent hydrophobicity. Here, polyethylene glycol (PEG) was incorporated as hydrophilic block to improve the acid-triggered drug release from the phosphazene-based crosslinked polyprodrug nanoparticles, besides the enhanced dispersibility and circulation time. With similar doxorubicin (DOX) content of ∼69 % and diameter of ∼130 nm, the HCCP-PEG_N-DOX nanoparticles synthesized with diamino polyethylene glycol (NH₂-PEG-NH₂) possessed a faster acid-triggered DOX release and in vitro antitumor efficiency than the HCCP-PEG_O-DOX synthesized with dihydroxy polyethylene glycol (HO-PEG-OH), although both ones exhibited a much faster DOX release from the reported HCCP-DOX nanoparticles synthesized without PEG, releasing more than 89 % of DOX in 84 h, and higher in vitro antitumor efficiency with lower half maximal inhibitory concentration (IC50) of 3.70 and 2.75 μg/mL than free DOX of 8.12 μg/mL.

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通过增强聚乙二醇的亲水性来改善肿瘤化疗用磷腈基交联聚前药纳米颗粒的药物释放性能

基于磷烯的交联多前药物纳米颗粒由于易于合成和敏感的ph触发降解，在肿瘤化疗中作为纳米级药物递送系统（nano- dds）受到了越来越多的关注。然而，由于其固有的疏水性，其分散性差，药物释放缓慢，限制了其实际应用。在本研究中，聚乙二醇（PEG）作为亲水性嵌段被加入到磷酸腈基交联聚前药纳米颗粒中，以改善酸触发的药物释放，并提高分散性和循环时间。与二氨基聚乙二醇（NH2-PEG-NH2）合成的HCCP-PEGO-DOX纳米颗粒相比，二氨基聚乙二醇（HO-PEG-OH）合成的HCCP-PEGO-DOX纳米颗粒具有更快的酸触发DOX释放和体外抗肿瘤效率，其含量为~ 69%，直径为~ 130 nm，尽管两种HCCP-PEGO-DOX纳米颗粒的DOX释放速度都要快得多，在84小时内释放超过89%的DOX。体外抗肿瘤效率较高，最大抑制浓度（IC50）分别为3.70和2.75 μg/mL，低于游离DOX的8.12 μg/mL。

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来源期刊

European Polymer Journal 化学-高分子科学

CiteScore

9.90

自引率

10.00%

发文量

691

审稿时长

23 days

期刊介绍： European Polymer Journal is dedicated to publishing work on fundamental and applied polymer chemistry and macromolecular materials. The journal covers all aspects of polymer synthesis, including polymerization mechanisms and chemical functional transformations, with a focus on novel polymers and the relationships between molecular structure and polymer properties. In addition, we welcome submissions on bio-based or renewable polymers, stimuli-responsive systems and polymer bio-hybrids. European Polymer Journal also publishes research on the biomedical application of polymers, including drug delivery and regenerative medicine. The main scope is covered but not limited to the following core research areas: Polymer synthesis and functionalization • Novel synthetic routes for polymerization, functional modification, controlled/living polymerization and precision polymers. Stimuli-responsive polymers • Including shape memory and self-healing polymers. Supramolecular polymers and self-assembly • Molecular recognition and higher order polymer structures. Renewable and sustainable polymers • Bio-based, biodegradable and anti-microbial polymers and polymeric bio-nanocomposites. Polymers at interfaces and surfaces • Chemistry and engineering of surfaces with biological relevance, including patterning, antifouling polymers and polymers for membrane applications. Biomedical applications and nanomedicine • Polymers for regenerative medicine, drug delivery molecular release and gene therapy The scope of European Polymer Journal no longer includes Polymer Physics.