title: Gambogic acid-loaded electrosprayed particles for site-specific treatment of hepatocellular carcinoma.
abstract: This study aims to assess the targeted effect and antitumor efficacy of Gambogic-acid-loaded particles (GA-Ps). GA-Ps with uniform particle sizes of 69.8 ± 17.8 nm (GA-P1), 185.6 ± 33.8 nm (GA-P2), 357.8 ± 81.5 nm (GA-P3), and 7.56 ± 0.95 μm (GA-P4) were prepared using an electrospray technique and exhibited extremely high entrapment efficiency. As the particle size increased from the nano- to microscale, the in vitro GA release rate sharply decreased. After tail-vein injection in mice, GA-P samples GA-P1, GA-P2, GA-P3, and GA-P4 improved the uptake of GA 1.67-times in the liver, 1.78-times in the liver, 2.18-times in the spleen, and 2.35-times in the lung, respectively, compared with GA solution (GA-S). The antitumor efficacy of GA-P2, with an 82.51% targeting efficiency (Te) for the liver, was examined in hepatocellular carcinoma (HCC) model mice. After 2 weeks of administration, HCC mice in the GA-P2 group exhibited a lower degree of tumor invasion and cell lesions in hepatic tissue, recovered liver function, and significantly prolonged survival time, compared with mice in the model, GA-S, and normal saline (NS) groups. Pharmacokinetic studies indicated that the superior antitumor efficacy of GA-P2 was attributed not only to tissue targeting but also to low clearance, extended retention, high bioavailability in plasma, and increased GA stability.
authors.affiliation: School of Pharmacy, Anhui University of Chinese Medicine , Hefei 230031, P. R. China.
authors.forename: Dengke
authors.initials: D
authors.lastname: Yin
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
authors.forename: Hanxu
authors.initials: H
authors.lastname: Cai
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Daiyin
authors.initials: D
authors.lastname: Peng
authors.forename: Liqing
authors.initials: L
authors.lastname: He
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival; D065546:Drug Liberation; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D044004:Xanthones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D008823:Micelles; D044004:Xanthones; C052659:gambogic acid
keywords: antitumor efficacy; electrospray; gambogic acid (GA); gambogic acid-loaded particle (GA-P); tissue targeting