Modified chitosan derivative micelle system for natural anti-tumor product gambogic acid delivery.
A chitosan derivative micelle system was developed as the delivery system for a novel anti-tumor drug, gambogic acid (GA). The physicochemical and pharmaceutical properties of GA-loaded micelles (GA-M) were evaluated compared with the formulation GA-L-arginine (GA-L) injection, which entered phase I clinical trials. The results showed that GA-M had high GA-loading rate (29.8 +/- 0.17%), high entrapment efficiency (63.8 +/- 0.52%), and small particle size (108.2 +/- 0.8 nm). After i.v. administration at the dose of 4 mg/kg, the area under concentration-time curve (AUC) and elimination half-life (T(1/2)beta) of GA-M were all increased by 1.7-fold compared with GA-L in rat. Biodistribution study indicated that approximately 67% of GA in the GA-M group was distributed in the liver, while the value of the GA-L group was approximately 55%. Additionally, GA amount in the kidney was greatly reduced in the GA-M group. Also, GA-M was shown to reduce the acute toxicity after i.v. administration in mice compared with GA-L. The present study indicated that GA was rapidly eliminated from the blood and transferred to the tissues, especially the liver. Moreover, GA acute toxicity and irritation to vein were decreased.
Qu
Guowei
G
College of Pharmacy, China Pharmaceutical University, Nanjing, PR China.
Zhu
Xian
X
Zhang
Can
C
Ping
Qineng
Q
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D008297:Male; D051379:Mice; D008823:Micelles; D051381:Rats; D017207:Rats, Sprague-Dawley; D044004:Xanthones / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity
D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D044004:Xanthones; C052659:gambogic acid; D048271:Chitosan