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Erschienen in: Cardiovascular Drugs and Therapy 6/2022

07.09.2021 | Original Article

HPMC improves protective effects of naringenin and isonicotinamide co-crystals against abdominal aortic aneurysm

verfasst von: Xing Zhang, Anyi Wang, Xiaotong Yang, Yunxia Wang, Qinyu Wang, Rui Hu, Gulinigaer Anwaier, Chang Di, Rong Qi, Yanbin Huang

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 6/2022

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Abstract

Purpose

Abdominal aortic aneurysm (AAA) rupture is one of the most common causes of mortality in cardiovascular diseases, but currently there is no approved drug for AAA treatment or prevention in the clinic. Naringenin (NGN) has been reported to have anti-AAA effects. However, water solubility and in vivo absorption of NGN are not satisfactory, which leads to its low bioavailability, thus affecting its pharmacological effects. In this project, the improving effects of isonicotinamide (INT) co-crystal and hydroxy propyl methyl cellulose (HPMC) or polyvinyl pyrrolidone (PVP) on the solubility, in vivo absorption, and anti-AAA effects of NGN were evaluated.

Methods

In the current study, co-crystals of naringenin-isonicotinamide (NGN-INT) were prepared, and effects of PVP or HPMC on precipitation rate, supersaturation, and bioavailability of NGN were explored. In addition, with or without HPMC supply, the effects of NGN-INT co-crystal on anti-AAA efficacy of NGN were investigated on an elastase-induced AAA mouse model, and the results were compared with the efficacy of the NGN crude drug.

Results

Our results demonstrate that NGN-INT formulation, compared to the NGN crude drug, enhanced the dissolution rate of NGN and significantly increased Cmax and AUC(0–∞) of NGN by 18 times and 1.97 times, respectively. Addition of PVP or HPMC in NGN-INT co-crystal further increased bioavailability of NGN in NGN-INT. The in vivo pharmacodynamic study showed that NGN-INT with HPMC significantly improved the inhibitory effects of NGN against AAA.

Conclusion

NGN-INT significantly improved the absorption and aortic protective effects of NGN. The supersaturation-prolonging effect of HPMC further enhanced bioavailability and anti-AAA effects of NGN-INT.

Graphical abstract

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Metadaten
Titel
HPMC improves protective effects of naringenin and isonicotinamide co-crystals against abdominal aortic aneurysm
verfasst von
Xing Zhang
Anyi Wang
Xiaotong Yang
Yunxia Wang
Qinyu Wang
Rui Hu
Gulinigaer Anwaier
Chang Di
Rong Qi
Yanbin Huang
Publikationsdatum
07.09.2021
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 6/2022
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-021-07206-x

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