Department of Pharmaceutical Technology, University of Innsbruck, Institute of Pharmacy, Center for Chemistry and Biomedicine, 6020 Innsbruck, Austria; Thiomatrix Forschungs- und Beratungs GmbH, Trientlgasse 65, 6020 Innsbruck, Austria.
Department of Pharmaceutical Technology, University of Innsbruck, Institute of Pharmacy, Center for Chemistry and Biomedicine, 6020 Innsbruck, Austria.
Int J Pharm. 2024 Apr 10;654:123983. doi: 10.1016/j.ijpharm.2024.123983. Epub 2024 Mar 7.
The study aimed to develop enzyme-degradable nanoparticles comprising polyphosphates and metal cations providing sustained release of the antibacterial drug ethacridine (ETH).
Calcium polyphosphate (Ca-PP), zinc polyphosphate (Zn-PP) and iron polyphosphate nanoparticles (Fe-PP NPs) were prepared by co-precipitation of sodium polyphosphate with cations and ETH. Developed nanocarriers were characterized regarding particle size, PDI, zeta potential, encapsulation efficiency and drug loading. Toxicological profile of nanocarriers was assessed via hemolysis assay and cell viability on human blood erythrocytes and HEK-293 cells, respectively. The enzymatic degradation of NPs was evaluated in presence of alkaline phosphatase (ALP) monitoring the release of monophosphate, shift in zeta potential and particle size as well as drug release. The antibacterial efficacy against Escherichia coli was determined via microdilution assay.
NPs were obtained in a size range between 300 - 480 nm displaying negative zeta potential values. Encapsulation efficiency was in the range of 83.73 %- 95.99 %. Hemolysis assay underlined sufficient compatibility of NPs with blood cells, whereas drug and NPs showed a concentration dependent effect on HEK-293 cells viability. Ca- and Zn-PP NPs exhibited remarkable changes in zeta potential, particle size, monophosphate and drug release upon incubation with ALP, compared to Fe-PP NPs showing only minor differences. The released ETH from Ca- and Zn-PP nanocarriers retained the antibacterial activity against E. coli, whereas no antibacterial effect was observed with Fe-PP NPs.
Polyphosphate nanoparticles cross-linked with divalent cations and ETH hold promise for sustained drug delivery triggered by ALP for parental administration.
本研究旨在开发包含多磷酸盐和金属阳离子的酶降解纳米粒子，以提供抗菌药物吖啶黄（ETH）的持续释放。
通过将多磷酸钠与阳离子共沉淀制备钙多磷酸盐（Ca-PP）、锌多磷酸盐（Zn-PP）和铁多磷酸盐纳米粒子（Fe-PP NPs）和 ETH。通过粒径、PDI、zeta 电位、包封效率和载药量对所开发的纳米载体进行了表征。通过溶血试验和人血红细胞和 HEK-293 细胞的细胞活力分别评估纳米载体的毒理学特征。通过监测单磷酸盐的释放、zeta 电位和粒径的变化以及药物释放来评估 NPs 的酶降解。通过微量稀释法测定了对大肠杆菌的抗菌功效。
获得了粒径在 300-480nm 之间的 NPs，显示出负 zeta 电位值。包封效率在 83.73%-95.99%之间。溶血试验表明 NPs 与血细胞具有足够的相容性，而药物和 NPs 对 HEK-293 细胞活力表现出浓度依赖性影响。与 Fe-PP NPs 相比，Ca-PP 和 Zn-PP NPs 在与 ALP 孵育时表现出明显的 zeta 电位、粒径、单磷酸盐和药物释放变化，而 Fe-PP NPs 仅显示出较小的差异。从 Ca-PP 和 Zn-PP 纳米载体释放的 ETH 保持了对大肠杆菌的抗菌活性，而 Fe-PP NPs 则没有观察到抗菌作用。
交联有二价阳离子和 ETH 的多磷酸盐纳米粒子有望通过 ALP 触发用于母体给药的持续药物释放。
