Honokiol nanosuspensions: preparation, increased oral bioavailability and dramatically enhanced biodistribution in the cardio-cerebro-vascular system.
Honokiol is a phytochemical component with multiple pharmacological activities, but Honokiol's wider use has been restricted by its poor solubility. Using bovine serum albumin and polyvinylpyrrolidone as stabilisers in a solvent precipitation-ultrasonication method, Honokiol nanosuspensions were prepared with a mean particle size of 116.2 nm (±2 nm), a zeta potential of -44.7 mV (±1.7 mV) and a high drug payload of 50.4 ± 0.6% (w/w). X-ray powder diffraction and differential scanning calorimetry indicated that Honokiol was in an amorphous state in the nanosuspensions, in contrast with bulk Honokiol powder. Honokiol was released faster in vitro from nanosuspensions with no burst release, and the highest 98% cumulative release was after 60 h. Honokiol nanosuspensions improved the oral bioavailability of Honokiol in in vivo studies in rats with a 3.94-fold Cmax and a 2.2-fold AUC(0-t). Remarkably, in contrast to oral administration, intraperitoneal administration of Honokiol nanosuspensions could dramatically alter the biodistribution of Honokiol, resulting in a much higher drug level and tissue bioavailability in the blood, heart and brain, benefitting the treatment of cardio-cerebro-vascular diseases.
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, PR China. Electronic address: hanmeihua727@163.com.
Meihua
M
Han
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, PR China; School of Pharmacy, Heilongjiang University of Chinese Medicine, No. 24, Heping Road, Xiangfang District, Harbin 150040, PR China. Electronic address: yuxin7878@163.com.
Xin
X
Yu
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, PR China. Electronic address: ffguo@163.com.
Yifei
Y
Guo
School of Pharmacy, Heilongjiang University of Chinese Medicine, No. 24, Heping Road, Xiangfang District, Harbin 150040, PR China. Electronic address: wang.yanhong@163.com.
Yanhong
Y
Wang
School of Pharmacy, Heilongjiang University of Chinese Medicine, No. 24, Heping Road, Xiangfang District, Harbin 150040, PR China. Electronic address: hxkuang56@163.com.
Haixue
H
Kuang
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, PR China. Electronic address: xtaowang@163.com.
Xiangtao
X
Wang
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D002560:Cerebrovascular Circulation; D003326:Coronary Circulation; D007668:Kidney / Q000378:metabolism; D017705:Lignans / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D013535:Suspensions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000498:Allyl Compounds; D010636:Phenols
D001713:Biphenyl Compounds; D017705:Lignans; D013535:Suspensions; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
Bioavailability; Biodistribution; Honokiol; Nanosuspensions; Preparation