Pharmacokinetics, pharmacodynamics, and tissue distribution of oral co-loaded puerarin/daidzein mixed micelles in rats.
10.19540/j.cnki.cjcmm.20230605.201
- Author:
Wen-Ting WU
1
;
Zi-Lu GUO
2
;
Shu-Chao GE
3
;
Wen-Liang KUANG
2
;
Wen-Dong LI
4
;
Shang-Dian WANG
2
;
Peng LIU
1
;
Zhi-Wei ZHOU
2
;
Wei-Feng ZHU
2
Author Information
1. School of Modern Chinese Medicine and Pharmaceutical Industry, Jiangxi University of Chinese Medicine Nanchang 330004, China.
2. Key Laboratory of Modern Preparation Chinese Materia Medica of Ministry of Education, Jiangxi University of Chinese Medicine Nanchang 330004, China.
3. School of Pharmacy, Jiangxi University of Chinese Medicine Nanchang 330004, China.
4. Zhejiang CONBA Pharmaceutical Co., Ltd. Hangzhou 310052, China.
- Publication Type:Journal Article
- Keywords:
daidzein;
pharmacodynamics;
pharmacokinetics;
polymer mixed micelles;
puerarin;
tissue distribution
- MeSH:
Rats;
Animals;
Micelles;
Tissue Distribution;
Chromatography, Liquid;
Tandem Mass Spectrometry;
Rats, Inbred SHR;
Isoflavones/pharmacology*
- From:
China Journal of Chinese Materia Medica
2023;48(18):5068-5077
- CountryChina
- Language:Chinese
-
Abstract:
This study investigated the drug delivery performance of oral co-loaded puerarin(PUE) and daidzein(DAZ) mixed micelles(PUE/DAZ-FS/PMMs) from the perspectives of pharmacokinetics, pharmacodynamics, and tissue distribution. The changes in PUE plasma concentration in rats were evaluated based on PUE suspension, single drug-loaded micelles(PUE-FS/PMMs), and co-loaded micelles(PUE/DAZ-FS/PMMs). Spontaneously hypertensive rats(SHR) were used to monitor systolic blood pressure, diastolic blood pressure, and mean arterial pressure for 10 weeks after administration by tail volume manometry. The content of PUE in the heart, liver, spleen, lung, kidney, brain, and testes was determined using LC-MS/MS. The results showed that compared with PUE suspension and PUE-FS/PMMs, PUE/DAZ-FS/PMMs significantly increased C_(max) in rats(P<0.01) and had a relative bioavailability of 122%. The C_(max), AUC_(0-t), AUC_(0-∞), t_(1/2), and MRT of PUE/DAZ-FS/PMMs were 1.77, 1.22, 1.22, 1.17, and 1.13 times higher than those of PUE suspension, and 1.76, 1.16, 1.08, 0.84, and 0.78 times higher than those of PUE-FS/PMMs, respectively. Compared with the model control group, PUE/DAZ-FS/PMMs significantly reduced systolic blood pressure, diastolic blood pressure, and mean arterial pressure in SHR rats(P<0.05). The antihypertensive effect of PUE/DAZ-FS/PMMs was greater than that of PUE suspension, and even greater than that of PUE-FS/PMMs at high doses. Additionally, the distribution of PMMs in various tissues showed dose dependency. The distribution of PMMs in the kidney and liver, which are metabolically related tissues, was lower than that in the suspension group, while the distribution in the brain was higher than that in the conventional dose group. In conclusion, PUE/DAZ-FS/PMMs not only improved the bioavailability of PUE and synergistically enhanced its therapeutic effect but also prolonged the elimination of the drug to some extent. Furthermore, the micelles facilitated drug penetration through the blood-brain barrier. This study provides a foundation for the development of co-loaded mixed micelles containing homologous components.
