| Objective:Gambogenic acid is one of the main active ingredients isolated from Garcinia cambogia.It has been found that Gambogenic acid possesses diverse anti-tumor activities with the potential as an antitumor drug.However,its poor solubility,short biological half-life,low oral bioavailability and excessive vascular irritation severely limit its clinical application.Phospholipids,the major components of cell membranes,had been widely used in drug delivery systems,including self-nanoemulsifying drug delivery systems,liposomes,oily gels and phospholipid complexe.Phospholipid complexe,was formed by intermolecular hydrogen bonds and electrostatic attraction between drug and phospholipids.After complexation,both the solubility and the permeability of poorly water-soluble compounds may be increased,and bioavailability was thereby improved.As a novel drug carrier,nanoparticles have the characteristics of small size and large specific surface area to reach sustained-release and increase oral absorption of drugs.Zein is a hydrophobic protein in corn with good biocompatibility,biodegradability,film-forming ability and amphipathicity as a nano-carrier.Herein,Phospholipid-modified Gambogenic acid was encapsulated in Zein to form Gambogenic acid/Zein nanoparticles,in order to enhance the oral bioavailability,prolong the circulation time.Methods:Gambogenic acid/Zein nanoparticles were prepared by the nano-deposition method using Zein as drug carrier,P188 as surfactant.Malvern laser particle size analyzer,Scanning electron microscope,differential scanning calorimetry,fourier transform infrared spectroscopy,X-ray diffraction and in vitro release were performed to characterize the particle size,polydispersity index,morphology,crystal form,chemical structure and in vitro release behavior of Gambogenic acid/Zein nanoparticles.At last,the in vivo pharmacokinetics of Gambogenic acid/Zein nanoparticles was investigated in rats.Results:The particle size,polydispersity index,Zeta potential and encapsulation efficiency of the optimized prescription were 102.90 nm,0.027 and 76.35±0.64%,respectively.The results of scanning electron microscope showed that the Gambogenic acid/Zein nanoparticles were spherical.The differential scanning calorimetry results indicated that Gambogenic acid in nanoparticle was in amorphous state.In comparison to Gambogenic acid,the Gambogenic acid/Zein nanoparticles showed slow-release effect.In pharmacokinetic experiments,the AUC,MRT and t1/2/2 of the Gambogenic acid/Zein nanoparticles were 1.27-fold,2.49-fold and 4.02-fold higher than Gambogenic acid solution.Tissue distribution study in rat was found that the concentration of Gambogenic acid/Zein nanoparticles in heart,liver,spleen,kidney,intestinal tissues was improved than Gambogenic acid solution.In the liver tissue,the concentration of Gambogenic acid in Gambogenic acid/Zein nanoparticles group was significantly higher than that of Gambogenic acid raw drug group.The concentration of the Gambogenic acid/Zein nanoparticles in liver tissue were 2.05-fold than Gambogenic acid solution.The results indicate that the distribution of Gambogenic acid in Gambogenic acid/Zein nanoparticles was significantly improved in rats'liver.Conclusion:The Gambogenic acid/Zein nanoparticles was successfully prepared by the nano-deposition method.In comparison with raw drug,the physicochemical properties of Gambogenic acid in Gambogenic acid/Zein nanoparticles have been changed and the in vivo pharmacokinetic parameters have been improved observably.This study provides a reference for the development of oral formulations of Gambogenic acid. |
PDF Full Text Request