A novel nanosuspension of andrographolide: Preparation, characterization and passive liver target evaluation in rats.
Andrographolide (Andro) is an excellent anti-inflammatory bicyclic diterpene γ-lactone. However, the poor solubility limits its application as injection for the treatment of acute inflammation. To meet the clinical needs for emergency, the Andro nanosuspensions injection was first prepared by the wet milling technique. The Andro nanosuspensions were composed of 3% Andro, 5% poloxamer 188 as the non-ionic stabilizer, 0.05% sodium deoxycholate or 0.1% sodium tauroursodeoxy cholate as the ionic stabilizer, and prepared by 350rpm speed and 12cycles of grinding with 0.4mm zirconium oxide pearls. The nanosuspensions showed hexagonal morphology with particle size of 300nm, and no change in crystalline state of Andro after milling. The nanosuspensions had a significant increase in saturation solubility, and could completely release within 0.25h (bulk Andro within 24h). The lyophilized product of Andro nanosuspensions with mannitol (5%) as lyoprotectant had good physical and chemical stability during the 6-month storage period. The pharmacokinetic and tissue distribution results showed that it was rapidly eliminated from the blood and largely distributed in the liver. Overall, the Andro nanosuspensions may be used as a potential formulation for the treatment of liver infections owing to its passive liver targeting function.
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China.
Ligang
L
Guo
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China.
Le
L
Kang
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China.
Xinrong
X
Liu
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China.
Xiangyun
X
Lin
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China.
Donghua
D
Di
Shineway Pharmaceutical Co. Ltd., 682 Yingbin Road, Sanhe, Hebei 065201, PR China.
Yong
Y
Wu
Shineway Pharmaceutical Co. Ltd., 682 Yingbin Road, Sanhe, Hebei 065201, PR China.
Dexian
D
Kong
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China.
Yihui
Y
Deng
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China. Electronic address: songyanzhi@syphu.edu.cn.
Yanzhi
Y
Song
D000818:Animals; D002152:Calorimetry, Differential Scanning; D004224:Diterpenes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D004355:Drug Stability; D006207:Half-Life; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology; D033362:Powder Diffraction; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D013535:Suspensions; D014018:Tissue Distribution
D004224:Diterpenes; D013535:Suspensions; C030419:andrographolide
Andrographolide; Nanosuspensions; Passive liver target; Wet milling technique