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A facile quantification of hyaluronic acid and its crosslinking using gas-phase electrophoresis

  • Hung-Li Wang
  • Chin-Ping Huang
  • Chiu-Hun Su
  • De-Hao TsaiEmail author
Research Paper
  • 33 Downloads

Abstract

We report a facile, high-resolution approach to quantitatively characterize hyaluronic acid (HA) and study its crosslinking reaction using electrospray-differential mobility analysis (ES-DMA). Mobility size distributions, number concentrations, molecular mass distributions, and polydispersity index of HAs were obtained successfully via a rapid analysis by ES-DMA (< 30 min). The limit of detection, the limit of quantification, and the precision of the mobility size measurement achieve 2.5 nm, 4.0 nm, and 0.3 nm, respectively. Size exclusion chromatography (SEC) was employed as an orthogonal approach, showing that the averaged molecular mass and polydispersity index of HA measured by ES-DMA were close to the results of SEC on a semi-quantitative basis. The 1,4-butanediol diglycidyl ether (BDDE)-induced crosslinking of HA was also able to be successfully characterized through a time-dependent study using ES-DMA, which has shown the promise of direct analysis of solution-based reactions. Both the extent and the rate of HA crosslinking (induced by BDDE) were proportional to reaction temperature and concentration ratio of HA to BDDE. The activation energy of the reaction-limited BDDE-induced crosslinking of HA was found to be ≈ 21 kJ/mol. The prototype study demonstrates ES-DMA as a new method for a rapid quantitative characterization of HA and its derivative product and providing a capability of real-time monitoring of the HA crosslinking during formulation process.

Graphical abstract

Keywords

Hyaluronic acid Mobility Electrospray Molecular mass Concentration Crosslinking 

Notes

Funding information

This study received financial support from the Ministry of Science and Technology of the Republic of China (Taiwan) under contract MOST 105-2221-E-007-129-MY3 and MOST 106-3113-E-007-002.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2019_1584_MOESM1_ESM.pdf (895 kb)
ESM 1 (PDF 894 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Hung-Li Wang
    • 1
  • Chin-Ping Huang
    • 2
  • Chiu-Hun Su
    • 2
  • De-Hao Tsai
    • 1
    Email author
  1. 1.Department of Chemical EngineeringNational Tsing Hua UniversityHsinchuRepublic of China
  2. 2.Material and Chemical Research LaboratoriesIndustrial Technology Research InstituteHsinchuRepublic of China

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