Nanosuspensions as delivery system for gambogenic acid: characterization and in vitro/in vivo evaluation.
Nanosuspensions (NS) can enhance the saturation solubility and dissolution velocity of poorly soluble drugs. PEG as a non-ionic surfactant plays an important role in surface modification of nanoparticles for prolonging in vivo circulation. In this study, anti-solvent precipitation method was introduced to prepare gambogenic acid nanosuspensions (GNA-NS) with PVPK30 and PEG2000 as stabilizers to settle the disadvantages of GNA. The obtained nanoparticles were spherical with a mean particle size of 183.7 nm and a zeta potential of -22.8 mV. The entrapment efficiency and drug loading of the resultant formulation were 97.3 and 29.73%. X-ray diffraction analysis confirmed the amorphous phase of GNA in NS. Fourier transform infrared indicated there may be hydrogen bond interaction between the drug and excipients. After lyophilization of GNA-NS, the freeze-dried powder displayed sufficient long-term physical stability at 4 and 25 °C. In comparison to GNA solution, in vitro studies of GNA-NS showed much slower release and higher cytotoxicity in HepG2 cells. What's more, the pharmacokinetic study in rats revealed that the AUC0-∞and t1/2of GNA-NS were increased 2.63- and 1.77-fold than that of the reference formulation. Taken together, in vitro/in vivo evaluations showed NS would be an effectively strategy to change the poor aqueous solubility and prolong the half-life for GNA. The GNA-NS with enhanced bioavailability and drug efficacy provided a promising delivery system for the application of GNA.
a Pharmacokinetics Laboratory , School of pharmacy, Anhui University of Chinese Medicine, Anhui Academy of Chinese Medicine , Hefei , People's Republic of China.
Huiling
H
Yuan
a Pharmacokinetics Laboratory , School of pharmacy, Anhui University of Chinese Medicine, Anhui Academy of Chinese Medicine , Hefei , People's Republic of China.
Xin
X
Li
a Pharmacokinetics Laboratory , School of pharmacy, Anhui University of Chinese Medicine, Anhui Academy of Chinese Medicine , Hefei , People's Republic of China.
Caiyun
C
Zhang
a Pharmacokinetics Laboratory , School of pharmacy, Anhui University of Chinese Medicine, Anhui Academy of Chinese Medicine , Hefei , People's Republic of China.
Wenli
W
Pan
a Pharmacokinetics Laboratory , School of pharmacy, Anhui University of Chinese Medicine, Anhui Academy of Chinese Medicine , Hefei , People's Republic of China.
Yumeng
Y
Liang
a Pharmacokinetics Laboratory , School of pharmacy, Anhui University of Chinese Medicine, Anhui Academy of Chinese Medicine , Hefei , People's Republic of China.
Yang
Y
Chen
a Pharmacokinetics Laboratory , School of pharmacy, Anhui University of Chinese Medicine, Anhui Academy of Chinese Medicine , Hefei , People's Republic of China.
Weidong
W
Chen
a Pharmacokinetics Laboratory , School of pharmacy, Anhui University of Chinese Medicine, Anhui Academy of Chinese Medicine , Hefei , People's Republic of China.
Lulu
L
Liu
a Pharmacokinetics Laboratory , School of pharmacy, Anhui University of Chinese Medicine, Anhui Academy of Chinese Medicine , Hefei , People's Republic of China.
Xiaomin
X
Wang
D000818:Animals; D001682:Biological Availability; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D005260:Female; D005612:Freeze Drying / Q000379:methods; D006207:Half-Life; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols; D011145:Polyvinyls / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D013535:Suspensions / Q000008:administration & dosage / Q000737:chemistry*; D014966:Xanthenes / Q000008:administration & dosage* / Q000737:chemistry*
D005079:Excipients; D011145:Polyvinyls; D012997:Solvents; D013501:Surface-Active Agents; D013535:Suspensions; D014966:Xanthenes; C488580:poly(vinyl phenyl ketone); D011092:Polyethylene Glycols; C045863:neo-gambogic acid
Cytotoxicity; gambogenic acid; in vitro release; in vivo pharmacokinetics; nanosuspensions