Stabilized micelles as delivery vehicles for paclitaxel.
Paclitaxel is an antineoplastic drug used against a variety of tumors, but its low aqueous solubility and active removal caused by P-glycoprotein in the intestinal cells hinder its oral administration. In our study, new type of stabilized Pluronic micelles were developed and evaluated as carriers for paclitaxel delivery via oral or intravenous route. The pre-stabilized micelles were loaded with paclitaxel by simple solvent/evaporation technique achieving high encapsulation efficiency of approximately 70%. Gastrointestinal transit of the developed micelles was evaluated by oral administration of rhodamine-labeled micelles in rats. Our results showed prolonged gastrointestinal residence of the marker encapsulated into micelles, compared to a solution containing free marker. Further, the oral administration of micelles in mice showed high area under curve of micellar paclitaxel (similar to the area of i.v. Taxol(®)), longer mean residence time (9-times longer than i.v. Taxol(®)) and high distribution volume (2-fold higher than i.v. Taxol(®)) indicating an efficient oral absorption of paclitaxel delivered by micelles. Intravenous administration of micelles also showed a significant improvement of pharmacokinetic parameters of micellar paclitaxel vs. Taxol(®), in particular higher area under curve (1.2-fold), 5-times longer mean residence time and lower clearance, indicating longer systemic circulation of the micelles.
Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, 2 Dunav Str., 1000 Sofia, Bulgaria. krassi.yoncheva@gmail.com
Krassimira
K
Yoncheva
Patricia
P
Calleja
Maite
M
Agüeros
Petar
P
Petrov
Ivanka
I
Miladinova
Christo
C
Tsvetanov
Juan M
JM
Irache
D000179:Acrylates / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D020442:Poloxamer / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D000179:Acrylates; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; D011409:Propylene Glycols; D020442:Poloxamer; D017239:Paclitaxel; C027992:pentaerythrityl triacrylate