配体分布和密度对双靶向叶酸/生物素Pluronic F127/聚乳酸聚合体靶向性的影响

IF 4.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-11-29 DOI:10.1016/j.ejpb.2024.114598

Qing Xiao Wang, Zi Ling Li, Yan Chun Gong, Xiang Yuan Xiong

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引用次数: 0

摘要

由于肿瘤的复杂性和异质性，用两种或两种以上配体修饰的靶向药物递送系统预计比仅用一种配体修饰的靶向药物递送系统具有更好的抗肿瘤能力。为此，设计了含有生物素（BT）和叶酸（FA）配体的双靶向Pluronic/poly（乳酸）聚合体（BT/FA- f127 - pla），研究其对人卵巢癌细胞（OVCAR-3）的靶向性。制备了两种双配体靶向聚合体BT/FA-F127-PLA和(BT + FA)-F127-PLA，研究双配体分布对聚合体细胞靶向性的影响。BT/FA-F127-PLA有两个配体分布在同一聚合体中，而(BT + FA)-F127-PLA有两个配体分布在不同的聚合体中。BT/FA-F127-PLA的体外细胞毒性、细胞摄取及体内药代动力学行为均优于(BT + FA)-F127-PLA。提示生物素和叶酸配体分布在同一聚合体上可能具有协同促进的靶向作用。对聚合体的细胞摄取机制的进一步实验表明，靶向聚合体的摄取与能量依赖性内吞作用有关，包括网格蛋白、小窝蛋白、巨噬细胞和配体受体介导的内吞作用。此外，进一步研究了不同密度比的双配体对BT/FA-F127-PLA的影响。结果表明，当生物素与叶酸的摩尔比为7.5%:7.5%时，BT/FA-F127-PLA的细胞靶向作用最强。综上所述，BT/FA-F127-PLA双靶向聚合体可作为靶向给药载体。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

The effects of ligand distribution and density on the targeting properties of dual-targeting folate/biotin Pluronic F127/Poly (lactic acid) polymersomes

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The effects of ligand distribution and density on the targeting properties of dual-targeting folate/biotin Pluronic F127/Poly (lactic acid) polymersomes

Targeted drug delivery systems modified with two or more ligands were expected to have better anti-tumor ability than those with just one ligand due to the complexity and heterogeneity of tumors. Thus, dual-targeting Pluronic/poly (lactic acid) polymersomes containing biotin (BT) and folic acid (FA) ligands (BT/FA-F127-PLA) were designed to study their targeting properties over human ovarian cancer cells (OVCAR-3). Two kinds of dual-ligand targeting polymersomes, BT/FA-F127-PLA and (BT + FA)-F127-PLA, were prepared to study the effect of the dual-ligand distribution on the cell targeting of polymersomes. BT/FA-F127-PLA had two ligands distributed in the same polymersomes whereas (BT + FA)-F127-PLA had two ligands distributed in different polymersomes. The in vitro cytotoxicity and cellular uptake, and in vivo pharmacokinetic behaviors of BT/FA-F127-PLA were superior to those of (BT + FA)-F127-PLA. It suggested that biotin and folate ligands distributed on the same polymersomes could have the targeting effect of synergistic promotion. Further experiments on cell uptake mechanisms of polymersomes showed that the uptake of targeted polymersomes was associated with energy-dependent endocytosis, involving clathrin, caveolin protein, macropinocytosis and ligand receptor-mediated endocytosis. In addition, the effect of different density ratios of dual ligands for BT/FA-F127-PLA was further studied. The results showed that the cellular targeting effect of BT/FA-F127-PLA was the strongest when the molar ratio of biotin to folic acid was 7.5 %: 7.5 %. In conclusion, BT/FA-F127-PLA dual-targeting polymersomes could be good candidates as targeted drug delivery carriers.

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来源期刊

European Journal of Pharmaceutics and Biopharmaceutics 医学-药学

CiteScore

8.80

自引率

4.10%

发文量

211

审稿时长

36 days

期刊介绍： The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.