HPMC improves protective effects of naringenin and isonicotinamide co-crystals against abdominal aortic aneurysm
| Autor: | Rui Hu, Yunxia Wang, Rong Qi, Anyi Wang, Xiaotong Yang, Qinyu Wang, Yanbin Huang, Chang Di, Gulinigaer Anwaier, Xing Zhang |
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| Rok vydání: | 2021 |
| Předmět: |
Naringenin
macromolecular substances Absorption (skin) Crude drug Pharmacology Mice chemistry.chemical_compound Hypromellose Derivatives In vivo medicine Animals Pharmacology (medical) Isonicotinamide Solubility business.industry technology industry and agriculture Povidone General Medicine medicine.disease Abdominal aortic aneurysm Bioavailability chemistry Cardiology and Cardiovascular Medicine business Aortic Aneurysm Abdominal |
| Zdroj: | Cardiovascular Drugs and Therapy. 36:1109-1119 |
| ISSN: | 1573-7241 0920-3206 |
| Popis: | 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.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.Our results demonstrate that NGN-INT formulation, compared to the NGN crude drug, enhanced the dissolution rate of NGN and significantly increased Csubmax/suband AUCsub(0-∞)/subof 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.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. |
| Databáze: | OpenAIRE |
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