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定量含环糊精气溶胶的吸湿性,以将药物递送到肺部。

Quantifying the hygroscopic properties of cyclodextrin containing aerosol for drug delivery to the lungs.

机构信息

Chemistry, School of Natural and Environmental Sciences, Bedson Building, Newcastle University, Newcastle Upon Tyne, NE1 7RU, UK.

出版信息

Phys Chem Chem Phys. 2020 May 28;22(20):11327-11336. doi: 10.1039/d0cp01385d. Epub 2020 May 14.

DOI:10.1039/d0cp01385d
PMID:32406900
Abstract

Aerosol dynamics is important to quantify in drug delivery to the lungs with the aim of delivering therapeutics to a target location and optimising drug efficacy. The macrocycle (2-hydroxypropyl)-β-cyclodextrin (2-HP-β-CD) is thought to alleviate symptoms associated with neurodegenerative diseases when inhaled but the hygroscopic response is not well understood. Here we measure the hygroscopic growth of individual aqueous aerosol containing 2-HP-β-CD in optical tweezers through analysis of morphology-dependent resonances arising in Raman spectra. Droplets are analysed in the size range of 3-5 μm in radius. The evolving radius and refractive index of each droplet are measured in response to change in relative humidity from 98-20% to determine mass and radius based hygroscopic growth factors, and compared with dynamic vapour sorption measurements. Bulk solution refractive index and density measurements were used in accordance with the self-consistent Lorenz-Lorentz rule to determine melt solute and droplet properties. The refractive index of 2-HP-β-CD was determined to be 1.520 ± 0.002 with a density of 1.389 ± 0.005 g cm. To our knowledge, we show the first aerosol measurements of 2-HP-β-CD and determine hygroscopicity. By quantifying the hygroscopic growth and physicochemical properties of 2-HP-β-CD, the impact of aerosol dynamics can be accounted for in tailoring drug formulations and informing models used to predict drug deposition patterns within the respiratory system.

摘要

气溶胶动力学对于肺部药物输送的定量研究非常重要,其目的是将治疗药物递送到目标部位并优化药物疗效。大环(2-羟丙基)-β-环糊精(2-HP-β-CD)被认为在吸入时可以缓解神经退行性疾病相关症状,但对其吸湿性的反应尚不清楚。在这里,我们通过分析拉曼光谱中出现的形态依赖共振,在光学镊子中测量含有 2-HP-β-CD 的单个水基气溶胶的吸湿性增长。在半径为 3-5μm 的范围内分析液滴。根据相对湿度从 98-20%的变化,测量每个液滴的半径和折射率的演变,以确定基于质量和半径的吸湿性增长因子,并与动态蒸汽吸附测量进行比较。根据自洽洛伦兹-洛伦兹规则,使用了溶液的折射率和密度测量值,以确定熔体溶质和液滴的性质。确定 2-HP-β-CD 的折射率为 1.520±0.002,密度为 1.389±0.005gcm。据我们所知,我们展示了对 2-HP-β-CD 的第一次气溶胶测量结果,并确定了其吸湿性。通过量化 2-HP-β-CD 的吸湿性增长和物理化学性质,可以在定制药物配方时考虑气溶胶动力学的影响,并为用于预测呼吸系统内药物沉积模式的模型提供信息。

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