Microfluidic Synthesis and Angiogenic Activity of Ginsenoside Rg1-Loaded PPF Microspheres

Mehrnaz Salarian; Raziye Samimi; William Z Xu; Zhiqiang Wang; Tsun-Kong Sham; Edmund M K Lui; Paul A Charpentier

doi:10.1021/acsbiomaterials.6b00222

Microfluidic Synthesis and Angiogenic Activity of Ginsenoside Rg₁-Loaded PPF Microspheres

ACS Biomater Sci Eng. 2016 Nov 14;2(11):1872-1882. doi: 10.1021/acsbiomaterials.6b00222. Epub 2016 Sep 2.

Authors

Mehrnaz Salarian^{1

2}, Raziye Samimi^{2

3}, William Z Xu³, Zhiqiang Wang⁴, Tsun-Kong Sham^{4

5}, Edmund M K Lui^{2

6}, Paul A Charpentier^{2

3}

Affiliations

¹ Biomedical Engineering Graduate Program, University of Western Ontario, London, Ontario N6A 5B9, Canada.
² The Ontario Ginseng Innovation & Research Consortium, London, Ontario N6A 5C1, Canada.
³ Chemical and Biochemical Engineering Department, University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 5B9, Canada.
⁴ Department of Chemistry, University of Western Ontario, London, Ontario N6A 5B7, Canada.
⁵ Soochow-Western Centre for Synchrotron Radiation Research, University of Western Ontario, London, Ontario N6A 5B7, Canada.
⁶ Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario N6A 5C1, Canada.

PMID: 33440524
DOI: 10.1021/acsbiomaterials.6b00222

Abstract

Next generation drug-loaded polymer scaffolds for hard tissue engineering require unique structures to enhance release kinetics while enabling bone cell growth (osteogenesis). This study examined the encapsulation of the pro-angiogenic mediator, ginsenoside Rg₁, into biodegradable poly(propylene fumarate) (PPF) microspheres to facilitate osteogenesis, while examining the release mechanism using advanced X-ray absorption near edge structure spectroscopy (XANES). Ginsenoside Rg₁-loaded PPF microspheres were prepared using both an emulsion method and a microfluidic device, with the microfluidic technique providing tunable unimodal PPF spheres ranging in size from 3 to 52 μm by varying the flow rates. The morphology and composition of the Rg₁-loaded PPF microspheres were characterized using FTIR, XRD, and XANES to examine the distribution of ginsenoside Rg₁ throughout the polymer matrix. Encapsulation efficiency and release profiles were studied and quantified by UV-Vis spectrophotometry, showing high encapsulation efficiencies of 95.4 ± 0.8% from the microfluidic approach. Kinetic analysis showed that Rg₁ release from the more monodisperse PPF microspheres was slower with a significantly smaller burst effect than from the polydisperse spheres, with the release following Fickian diffusion. The released Rg₁ maintained its angiogenic effect in vitro, showing that the PPF microspheres are promising to serve as vehicles for long-term controlled drug delivery leading to therapeutic angiogenesis in bone tissue engineering strategies.

Keywords: X-ray absorption near edge structure (XANES); angiogenesis; drug delivery; microfluidics; monodisperse microspheres; poly(propylene fumarate).