Chemistry, School of Natural and Environmental Sciences, Bedson Building, Newcastle University, Newcastle Upon Tyne, NE1 7RU, UK.
Phys Chem Chem Phys. 2020 May 28;22(20):11327-11336. doi: 10.1039/d0cp01385d. Epub 2020 May 14.
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.
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。