The Importance of Apparent pKa in the Development of Nanoparticles Encapsulating siRNA and mRNA

被引：138
作者：
Patel, Pratikkumar [1 ]
Ibrahim, Nurudeen Mohammed [1 ]
Cheng, Kun [1 ]
机构：
[1] Univ Missouri, Sch Pharm, Div Pharmacol & Pharmaceut Sci, 2464 Charlotte St, Kansas City, MO 64108 USA
来源：
TRENDS IN PHARMACOLOGICAL SCIENCES | 2021年 / 42卷 / 06期
基金：
美国国家卫生研究院;
关键词：
LIPID-LIKE MATERIALS; IN-VIVO; SYSTEMIC DELIVERY; ENDOSOMAL ESCAPE; TRANSFECTION; EFFICIENCY; CHITOSAN; POLYETHYLENIMINE; TRAFFICKING; VACCINES;
D O I：
10.1016/j.tips.2021.03.002
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Polymer and lipid nanoparticles have been extensively used as carriers to address the biological barriers encountered in siRNA and mRNA delivery. We summarize the crucial role of nanoparticle charge and ionizability in complexing RNAs, binding to biological components, escaping from the endosome, and releasing RNAs into the cytoplasm. We highlight the significant impact of the apparent pKa of nanoparticles on their efficacy and toxicity, and the importance of optimizing pKa in the development of lead formulations for RNAs. We also discuss the feasibility of fine-tuning the pKa in nanoparticles and the applications of this approach in the optimization of delivery systems for RNAs.
引用
收藏
页码：448 / 460
页数：13
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