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采用倾斜式电动力学注射器和水平喷涂平面的聚合物-药物纳米颗粒工程自适应方法。

An Adaptive Approach in Polymer-Drug Nanoparticle Engineering using Slanted Electrohydrodynamic Needles and Horizontal Spraying Planes.

机构信息

Leicester School of Pharmacy, De Montfort University, Leicester, UK.

Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.

出版信息

AAPS PharmSciTech. 2024 Oct 30;25(8):257. doi: 10.1208/s12249-024-02971-y.


DOI:10.1208/s12249-024-02971-y
PMID:39477831
Abstract

The present study focuses on the adaptive development of a key peripheral component of conventional electrohydrodynamic atomisation (EHDA) systems, namely spraying needles (also referred to as nozzles or spinnerets). Needle geometry and planar alignment are often overlooked. To explore potential impact, curcumin-loaded polylactic-co-glycolic acid (PLGA) and methoxypolyethylene glycol amine (PEG)-based nanoparticles were fabricated. To elucidate these technological aspects, a horizontal electrospraying needle regime was adapted, and three formulations containing different polymeric ratios of PLGA: PEG (50:50, 75:25, and 25:75) were prepared and utilised. Furthermore, processing head tip geometries e.g. blunt (a flat needle exit) or slanted (a 45° inclination angle), were subjected to various flow rates (5 µL-100 µL). Successful engineering of curcumin-loaded polymeric nanoparticles (< 150 nm) was observed. In-silico analysis demonstrated stable properties of curcumin, PEG and PLGA (molecular docking studies) and fluid flow direction towards the Taylor-Cone (also known as the stable jet mode), was shown by the assessment of fluid dynamics simulations in various needle outlets. Curcumin-loaded nanoparticles were characterised using an array of methods including Scanning electron microscopy, Differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, as well as their contact angles, encapsulation efficiencies and finally release patterns. The discrepancy when spraying with blunt and angled needles was evidenced by electron micrographs and deposition patterns. Spraying plumes utilising slanted needles enhanced particle collection efficiency and distribution of resultant atomised structures. In addition to needle design, fine-tuning the applied voltage and flow rate impacted the electrospraying process. The coefficient of variation was calculated as 30.5% and 25.6% for blunt and angled needle outlets, respectively, presenting improved particle uniformity with the employment of angled needle tips (8-G needle at 25 µL). The interplay of processing parameters with the utilisation of a slanted exit at a capillary optimised the spray pattern and formation of desired nanoparticulates. These demonstrate great applicability for controlled deposition and up-scaling processes in the pharmaceutical industry. These advances elaborate on EHDA processes, indicating a more cost-effective and scalable approach for industrial applications, facilitating the generation of a diverse range of particle systems in a controlled and more uniform fashion.

摘要

本研究集中于传统静电液滴喷射(EHDA)系统的一个关键外围组件的自适应发展,即喷涂针(也称为喷嘴或喷丝头)。通常会忽略针的几何形状和平面对准。为了探索潜在的影响,制备了负载姜黄素的聚乳酸-共-羟基乙酸(PLGA)和甲氧基聚乙二醇胺(PEG)基纳米颗粒。为了阐明这些技术方面,采用了水平电喷雾针模式,并制备和使用了三种含有不同 PLGA:PEG 聚合物比的配方(50:50、75:25 和 25:75)。此外,处理头尖端几何形状,例如平头(平针尖出口)或斜头(45°倾斜角),经受各种流速(5 µL-100 µL)。观察到负载姜黄素的聚合物纳米颗粒(<150nm)的成功工程化。计算机模拟分析表明姜黄素、PEG 和 PLGA 的稳定性能(分子对接研究),并且通过在各种针出口处评估流体动力学模拟,显示了流体流向泰勒锥(也称为稳定射流模式)。使用一系列方法对负载姜黄素的纳米颗粒进行了表征,包括扫描电子显微镜、差示扫描量热法、傅里叶变换红外光谱、X 射线衍射以及它们的接触角、包封效率和最终释放模式。通过电子显微镜照片和沉积模式证明了使用平头和斜头喷涂时的差异。使用斜头针喷射增强了颗粒收集效率和所得雾化结构的分布。除了针设计之外,微调施加的电压和流速会影响电喷雾过程。对于平头和斜头针出口,变异系数分别计算为 30.5%和 25.6%,表明使用斜头针尖端(25 µL 时的 8-G 针)可提高颗粒均匀性。加工参数的相互作用与在优化的毛细管上使用斜出口相结合,优化了喷雾模式和所需纳米颗粒的形成。这些在药物输送和大规模应用中展示了出色的适用性。这些进展详细阐述了 EHDA 工艺,表明了一种更具成本效益和可扩展的工业应用方法,以更可控和更均匀的方式生成各种颗粒系统。

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[3]
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[4]
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[5]
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[6]
Evaluation of sustained-release in-situ injectable gels, containing naproxen sodium, using in vitro, in silico and in vivo analysis.

Int J Pharm. 2022-3-25

[7]
Density Functional Theory and Molecular Docking Investigations of the Chemical and Antibacterial Activities for 1-(4-Hydroxyphenyl)-3-phenylprop-2-en-1-one.

Molecules. 2021-6-14

[8]
Electrohydrodynamic atomisation driven design and engineering of opportunistic particulate systems for applications in drug delivery, therapeutics and pharmaceutics.

Adv Drug Deliv Rev. 2021-9

[9]
Three-Dimensional Printing of Curcumin-Loaded Biodegradable and Flexible Scaffold for Intracranial Therapy of Glioblastoma Multiforme.

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[10]
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