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负载阿霉素的聚乳酸-羟基乙酸共聚物纳米粒经阳离子/阴离子聚电解质修饰：表征及其治疗效果

Doxorubicin Loaded PLGA Nanoparticle with Cationic/Anionic Polyelectrolyte Decoration: Characterization, and Its Therapeutic Potency.

作者信息

Tsai Li-Hui, Yen Chia-Hsiang, Hsieh Hao-Ying, Young Tai-Horng

机构信息

Department of Biomedical Engineering, National Taiwan University, Taipei 100, Taiwan.

Department of Dentistry, National Taiwan University Hospital, Taipei 100, Taiwan.

出版信息

Polymers (Basel). 2021 Feb 25;13(5):693. doi: 10.3390/polym13050693.

DOI:10.3390/polym13050693
PMID:33668941
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7956616/
Abstract

Optimized Doxorubicin hydrochloride (DOX) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (DPN) were prepared by controlling the water/oil distribution of DOX at different pH solutions and controlling the electrostatic interaction between DOX and different terminated-end PLGAs. Furthermore, cationic polyethylenimine (PEI) and anionic poly (acrylic acid) (PAA) were alternately deposited on DPN surface to form PEI-DPN (IDPN) and PAA-PEI-DPN (AIDPN) to enhance cancer therapy potency. Compared to DPN, IDPN exhibited a slower release rate in physiological conditions but PEI was demonstrated to increase the efficiency of cellular uptake and endo/lysosomal escape ability. AIDPN, with the outermost negatively charged PAA layer, still retained better endo/lysosomal escape ability compared to DPN. In addition, AIDPN exhibited the best pH-dependent release profile with 1.6 times higher drug release in pH 5.5 than in pH 7.4. Therefore, AIDPN with the characteristics of PEI and PAA simultaneously was the most optional cancer therapy choice within these three PLGA nanoparticles. As the proposed nanoparticles integrated optimal procedure factors, and possessed cationic and anionic outlayer, our drug delivery nanoparticles can provide an alternative solution to current drug delivery technologies.

摘要

通过控制不同pH溶液中盐酸多柔比星（DOX）的水/油分布以及DOX与不同端基聚乳酸-羟基乙酸共聚物（PLGA）之间的静电相互作用，制备了优化的负载DOX的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒（DPN）。此外，将阳离子聚乙烯亚胺（PEI）和阴离子聚丙烯酸（PAA）交替沉积在DPN表面，形成PEI-DPN（IDPN）和PAA-PEI-DPN（AIDPN），以提高癌症治疗效力。与DPN相比，IDPN在生理条件下表现出较慢的释放速率，但PEI被证明可提高细胞摄取效率和内吞/溶酶体逃逸能力。AIDPN具有最外层带负电荷的PAA层，与DPN相比，仍保留了更好的内吞/溶酶体逃逸能力。此外，AIDPN表现出最佳的pH依赖性释放曲线，在pH 5.5时的药物释放比在pH 7.4时高1.6倍。因此，同时具有PEI和PAA特性的AIDPN是这三种PLGA纳米颗粒中最理想的癌症治疗选择。由于所提出的纳米颗粒整合了最佳工艺因素，并具有阳离子和阴离子外层，我们的药物递送纳米颗粒可以为当前的药物递送技术提供替代解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e05c/7956616/58cfdf010711/polymers-13-00693-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e05c/7956616/e60148214a39/polymers-13-00693-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e05c/7956616/7788cd773bf3/polymers-13-00693-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e05c/7956616/20246b42f1c4/polymers-13-00693-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e05c/7956616/1fe26130773e/polymers-13-00693-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e05c/7956616/5f437917b1a5/polymers-13-00693-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e05c/7956616/ab82f366182c/polymers-13-00693-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e05c/7956616/58cfdf010711/polymers-13-00693-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e05c/7956616/e60148214a39/polymers-13-00693-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e05c/7956616/7788cd773bf3/polymers-13-00693-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e05c/7956616/20246b42f1c4/polymers-13-00693-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e05c/7956616/1fe26130773e/polymers-13-00693-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e05c/7956616/5f437917b1a5/polymers-13-00693-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e05c/7956616/ab82f366182c/polymers-13-00693-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e05c/7956616/58cfdf010711/polymers-13-00693-g007.jpg

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