Development of intravenous lipid emulsion of tanshinone IIA and evaluation of its anti-hepatoma activity in vitro.
The purpose of this study was to develop a lipid emulsion of tanshinone IIA (Tan IIA-LE) for intravenous administration and to investigate its feasibility for future clinical practice. The formulation was optimized using central composite design-response surface methodology (CCD-RSM), and the homogenization process was investigated systematically. The Tan IIA-LE was evaluated in terms of stability, safety and in vitro anti-hepatoma activity. The formulation of Tan IIA-LE is composed of 0.05% (w/v) Tan IIA, 20% (w/v) soybean oil-MCT mixture (1:1, w/w), 1.2% (w/v) soybean lecithin, 0.3% (w/v) F68 and 2.2% (w/v) glycerol, a high pressure homogenization at 100 MPa for 3 cycles was selected as the optimal homogenization process. The Tan IIA-LE was light-sensitive but stable for at least 12 months at room temperature in dark. The safety study demonstrated that the Tan IIA-LE did not cause venous irritation or obvious acute toxicity. Furthermore, the Tan IIA-LE displayed significant anti-tumor activity against human hepatoma cell lines in vitro. Overall, the Tan IIA-LE developed in this study was suggested to be a suitable and safe dosage form of Tan IIA for intravenous administration and has potential in liver cancer therapy in future.
Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17 Section 3 Southern Renmin Road, Chengdu, PR China.
Ting
T
Chu
Qing
Q
Zhang
Hui
H
Li
Wei-cong
WC
Ma
Na
N
Zhang
Hui
H
Jin
Sheng-jun
SJ
Mao
D045784:Abietanes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004355:Drug Stability; D005217:Fat Emulsions, Intravenous / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice; D011817:Rabbits
D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D005217:Fat Emulsions, Intravenous; C021751:tanshinone