Fabrication and in vitro/in vivo evaluation of amorphous andrographolide nanosuspensions stabilized by D-[alpha]-tocopheryl polyethylene glycol 1000 succinate/sodium lauryl sulfate

• Published in: International Journal of Nanomedicine 2017, Vol.12, p.1033
• Main Authors: Qiao, Hongzhi, Chen, Lihua, Rui, Tianqi, Wang, Jingxian, Chen, Ting, Fu, Tingming, Li, Junsong, Di, Liuqing
• Format: Report
• Language: English
• Subjects: Bioavailability; Chemical properties; Diterpenes; Innovations; Nanotechnology; Properties; Suspensions (Chemistry); Testing
• ISSN: 1178-2013
• DOI: 10.2147/IJN.S120887

Andrographolide (ADG) is a diterpenoid isolated from Andrographis paniculata with a wide spectrum of biological activities, including anti-inflammatory, anticancer and hepatoprotective effects. However, its poor water solubility and efflux by P-glycoprotein have resulted in lower bioavailability. In this study, ADG nanosuspensions (ADG-NS) were prepared using a wet media milling technique followed by freeze drying. D-[alpha]-Tocopheryl polyethylene glycol 1000 succinate (TPGS), a surfactant that inhibits P-glycoprotein function, and sodium lauryl sulfate were used as surface stabilizers. A Box-Behnken design was used to optimize the nanosuspension preparation. The products of these optimal preparation conditions were amorphous and possessed much faster dissolution in vitro than a coarse powder of ADG. The particle size and redispersibility index of the freeze-dried ADG-NS were 244.6[+ or -]3.0 nm and 113%[+ or -]1.14% (n=3), respectively. A short-term stability study indicated that the freeze-dried ADG-NS could remain highly stable as nanosuspensions during the testing period. A test of transport across a Caco-2 cell monolayer revealed that the membrane permeability ([P.sub.app]) of ADG-NS was significantly higher than the permeability of the ADG coarse powder or ADG-NS without TPGS (P