In vivo evaluation of lipid nanocapsules as a promising colloidal carrier for paclitaxel.
Paclitaxel-loaded lipid nanocapsules (PX-LNC) exhibit interesting in vitro characteristics with improved antitumoral activity compared with free PX formulation. Biodistribution studies were realized with the use of (14)C-trimyristin ((14)C-TM) or (14)C-phosphatidylcholine ((14)C-PC) whereas antitumoral activity of PX-LNC formulations was based on the animal survival in a chemically induced hepatocellular carcinoma (HCC) model in Wistar rats. Blood concentration-time profiles for both labeled (14)C-TM-LNC and (14)C-PC-LNC were similar; the t(1/2) and MRT values (over 2h and close to 3h, respectively, for both formulations) indicated the long circulating properties of the LNC carrier with a slow distribution and elimination phase. Survival curves of paclitaxel treated groups showed a statistical significant difference compared to the control survival curve (P=0.0036 and 0.0408). Animals treated with 4x 70 mg/m(2) of PX-LNC showed the most significant increase in mean survival times compared to the controls (IST(mean) 72%) and cases of long-term survivors were preferentially observed in the PX-LNC treated group (37.5%; 3/8). These results demonstrate the great interest to use LNC as drug delivery system for paclitaxel, permitting with an equivalent therapeutic efficiency to avoid the use of excipients such as polyoxyethylated castor oil for its formulation.
Lacoeuille
F
F
Inserm U646, 10 rue A. Boquel, F-49100 Angers, France. franck.lacoeuille@univ-angers.fr
Hindre
F
F
Moal
F
F
Roux
J
J
Passirani
C
C
Couturier
O
O
Cales
P
P
Le Jeune
J J
JJ
Lamprecht
A
A
Benoit
J P
JP
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D001682:Biological Availability; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000188:drug therapy / Q000401:mortality; D003102:Colloids; D004337:Drug Carriers; D004339:Drug Compounding; D006207:Half-Life; D008055:Lipids; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000401:mortality; D053769:Nanocapsules; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate
D000972:Antineoplastic Agents, Phytogenic; D003102:Colloids; D004337:Drug Carriers; D008055:Lipids; D053769:Nanocapsules; D017239:Paclitaxel