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

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

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-3. 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.

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin / chemistry*
  • Aerosols / chemistry*
  • Optical Tweezers
  • Spectrum Analysis, Raman
  • Wettability*

Substances

  • Aerosols
  • 2-Hydroxypropyl-beta-cyclodextrin