Nanostructured lipid carriers decorated with polyphosphate coated linear and loop cell-penetrating peptides

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics Pub Date : 2024-10-24 DOI:10.1016/j.ijpharm.2024.124844

Ahmad Saleh , Daniel Stengel , Martyna Truszkowska , Mariana Blanco Massani , Gergely Kali , Andreas Bernkop-Schnürch

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引用次数: 0

Abstract

Aim

This study aimed to evaluate the cellular uptake of nanostructured lipid carriers (NLCs) decorated with polyphosphate coated linear and loop cell-penetrating peptides (CPPs).

Methods

Linear-CPPs and loop-CPPs were synthesized via ring-opening polymerization and anchored on the surface NLCs, followed by coating with polyphosphate (PP). These nanocarriers (NCs) were characterized in terms of particle size, polydispersity index (PDI), and zeta potential. Cell viability and hemolysis, as well as enzyme-induced charge conversion via phosphate cleavage by free and membrane-bound intestinal alkaline phosphatase (IAP) were investigated. Cellular uptake studies by Caco-2 and HEK cells were quantitatively analyzed by flow cytometry and visualized by confocal microscopy.

Results

A shift in charge from positive to negative was obtained for both linear- and loop-CPPs-NLCs by coating with PP. PP-linear-CPPs-NLCs and PP-loop-CPPs-NLCs exhibited a particle size < 270 nm and a PDI of approximately 0.3. They had a minor effect on cell viability and caused in a concentration of 0.1 % (m/v) around 10 % hemolysis within 24 h. IAP triggered the cleavage and release of monophosphate from the surface of NLCs causing charge conversion from –22.2 mV to + 5.3 mV (Δ27.5 mV) for PP-linear-CPPs-NLCs and from −19.2 mV to + 11.9 mV (Δ31.1 mV) for PP-loop-CPPs-NLCs. Inhibition of alkaline phosphatase activity on Caco-2 and HEK cells confirmed the involvement of this enzyme in charge conversion. PP-linear-CPPs-NLCs showed on Caco-2 cells a higher uptake than PP-loop-CPPs-NLCs, whereas on HEK cells uptake of both types of NLCs was on the same level. The results of cellular uptake were confirmed visually by confocal microscopy.

Conclusion

CPPs-NLCs coated with polyphosphate are a promising approach to overcome the polycationic dilemma and to enhance cellular uptake.

Abstract Image

查看原文本刊更多论文

用聚磷酸酯线性和环形细胞穿透肽装饰的纳米结构脂质载体。

目的：本研究旨在评估用聚磷酸酯包覆线性和环状细胞穿透肽（CPPs）装饰的纳米结构脂质载体（NLCs）的细胞吸收情况：方法：通过开环聚合合成线性和环状细胞穿透肽（CPPs），并将其固定在纳米脂质载体（NLCs）表面，然后涂上聚磷酸盐（PP）。这些纳米载体（NCs）在粒度、多分散指数（PDI）和ZETA电位方面均有特征。研究了细胞活力、溶血以及游离和膜结合的肠道碱性磷酸酶（IAP）通过磷酸盐裂解诱导的电荷转移。通过流式细胞仪对 Caco-2 和 HEK 细胞的细胞摄取研究进行了定量分析，并用共聚焦显微镜进行了观察：结果：涂覆 PP 后，线型和环型 CPPs-NLC 的电荷均由正向转变为负向。PP-linear-CPPs-NLCs 和 PP-loop-CPPs-NLCs 显示出粒度结论：涂有聚磷酸盐的 CPPs-NLCs 是克服多阳离子困境和提高细胞吸收率的一种可行方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Pharmaceutics 医学-药学

CiteScore

10.70

自引率

8.60%

发文量

951

审稿时长

72 days

期刊介绍： The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.