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Planta Med 2019; 85(16): 1233-1241
DOI: 10.1055/a-1013-1276
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Development and Characterization of the Neuroregenerative Xanthohumol C/Hydroxypropyl-β-cyclodextrin Complex Suitable for Parenteral Administration

Michael Kirchinger‡
1   Organic-Analytical Chemistry, Weihenstephan-Triesdorf University of Applied Sciences, Straubing, Germany
2   TUM Campus Straubing, Straubing, Germany
,
Lara Bieler‡
3   Institute of Experimental Neuroregeneration, Paracelsus Medical University Salzburg, Salzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria
,
Julia Tevini
4   Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria
,
Michael Vogl
3   Institute of Experimental Neuroregeneration, Paracelsus Medical University Salzburg, Salzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria
,
Elisabeth Haschke-Becher
4   Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria
,
Thomas K. Felder
4   Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria
5   Obesity Research Unit, Paracelsus Medical University, Salzburg, Austria
,
Sebastien Couillard-Després
3   Institute of Experimental Neuroregeneration, Paracelsus Medical University Salzburg, Salzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria
6   Austrian Cluster for Tissue Regeneration, Salzburg, Austria
,
Herbert Riepl
1   Organic-Analytical Chemistry, Weihenstephan-Triesdorf University of Applied Sciences, Straubing, Germany
2   TUM Campus Straubing, Straubing, Germany
,
Corinna Urmann
1   Organic-Analytical Chemistry, Weihenstephan-Triesdorf University of Applied Sciences, Straubing, Germany
2   TUM Campus Straubing, Straubing, Germany
› Author Affiliations
Further Information

Publication History

received 16 April 2019
revised 12 September 2019

accepted 12 September 2019

Publication Date:
14 October 2019 (online)

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Abstract

The chroman-like chalcone Xanthohumol C, originally found in hops, was demonstrated to be a potent neuroregenerative and neuroprotective natural product and therefore constitutes a strong candidate for further pharmaceutical research. The bottleneck for in vivo experiments is the low water solubility of this chalcone. Consequently, we developed and validated a suitable formulation enabling in vivo administration. Cyclodextrins were used as water-soluble and nontoxic complexing agents, and the complex of Xanthohumol C and 2-hydroxypropyl-β-cyclodextrin was characterized using HPLC, HPLC-MS, NMR, and differential scanning calorimetry. The water solubility of Xanthohumol C increases with increasing concentrations of cyclodextrin. Using 50 mM 2-hydroxypropyl-β-cyclodextrin, solubility was increased 650-fold. Furthermore, in vitro bioactivity of Xanthohumol C in free and complexed form did not significantly differ, suggesting the release of Xanthohumol C from 2-hydroxypropyl-β-cyclodextrin. Finally, a small-scaled in vivo experiment in a rat model showed that after i. p. administration of the complex, Xanthohumol C can be detected in serum, the brain, and the cerebrospinal fluid at 1 and 6 h post-administration. Mean (± SD) Xanthohumol C serum concentrations after 1, 6, and 12 h were determined as 463.5 (± 120.9), 61.9 (± 13.4), and 9.3 (± 0.8) ng/mL upon i. v., and 294.3 (± 22.4), 45.5 (± 0.7), and 13 (± 1.0) ng/mL after i. p. application, respectively. Accordingly, the formulation of Xanthohumol C/2-hydroxypropyl-β-cyclodextrin is suitable for further in vivo experiments and further pharmaceutical research aiming for the determination of its neuroregenerative potential in animal disease models.

Key words

Xanthohumol C - drug solubilization - bioavailability - cyclodextrin - Cannabaceae
 

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