In vivo evaluation of paclitaxel-loaded lipid nanocapsules after intravenous and oral administration on resistant tumor.
OBJECTIVE
The aim of the present work was to encapsulate paclitaxel (Ptx) in various lipid nanocapsules (LNCs) formulations and then to compare their pharmacokinetics and efficacy on a subcutaneous isograft model in rats.


RESULTS
Three different Ptx formulations were obtained. Drug payloads ranged from 1.32 to 3.62 mg Ptx/g of formulation. After oral administration the area under concentration-time curve was higher (p < 0.05) if Ptx was encapsulated, (1,2 Distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(PEG)] (DSPE-PEG-NH2)) LNCs displaying the highest area under concentration-time curve (p < 0.05). Efficacy was better than control for standard LNCs after oral administration (p < 0.05) and for (DSPE-PEG-NH2) LNCs after intravenous administration. Despite good absorption, (DSPE-PEG-NH2) LNCs failed to remain efficient after oral route.


CONCLUSIONS
This study highlights the importance of efficacy studies paired to pharmacokinetic studies for nanomedicines.
INSERM U1066 MINT, Micro et Nanomédecines Biomimétiques, LUNAM Université, 4 Rue Larrey, 49033 Angers, CEDEX 09, France.
A C
AC
Groo
M
M
Bossiere
L
L
Trichard
P
P
Legras
J P
JP
Benoit
F
F
Lagarce
D000284:Administration, Oral; D000586:Amination; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002460:Cell Line; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007275:Injections, Intravenous; D053769:Nanocapsules / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D011916:Rats, Inbred F344
D000972:Antineoplastic Agents, Phytogenic; D053769:Nanocapsules; D010714:Phosphatidylethanolamines; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D017239:Paclitaxel
cancer; nanoparticles; oral route; paclitaxel; pharmacodynamics; pharmacokinetics; rats