Pharmacokinetics and antitumor efficacy of paclitaxel-cyclodextrin complexes loaded in mucus-penetrating nanoparticles for oral administration.
OBJECTIVE
The authors report a novel approach for enhancing the oral absorption of paclitaxel (PTX) by encapsulation in poly(anhydride) nanoparticles (NPs) containing cyclodextrins and poly(ethylene glycol).


METHODS
Formulations were prepared using the solvent displacement method. Subsequently, pharmacokinetics and organ distribution assays were evaluated after oral administration into C57BL/6J mice. In addition, antitumor efficacy studies were performed in a subcutaneous tumor model of Lewis lung carcinoma.


RESULTS
PTX-loaded NPs displayed sizes between 190-300 nm. Oral NPs achieved drug plasma levels for at least 24 h, with an oral bioavailability of 55-80%. Organ distribution studies revealed that PTX, orally administered in NPs, underwent a similar distribution to intravenous Taxol(®) (Bristol-Myers Squibb, NJ, USA). For in vivo antitumor assays, oral strategy maintained a slower tumor growth than intravenous Taxol.


CONCLUSIONS
PTX orally administered in poly(anhydride) NPs, combined with cyclodextrins and poly(ethylene glycol), displayed sustained plasma levels and significant antitumor effect in a syngenic tumor model of carcinoma in mice.
Department of Pharmacy & Pharmaceutical Technology, School of Pharmacy, University of Navarra, Calle de Irunlarrea, 1, 31080, Pamplona, Spain.
Patricia
P
Calleja
Socorro
S
Espuelas
Leticia
L
Corrales
Ruben
R
Pio
Juan M
JM
Irache
D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D009093:Mucus; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution
D003505:Cyclodextrins; D017239:Paclitaxel
antitumor efficacy; cyclodextrin; nanoparticle; oral chemotherapy; paclitaxel; pharmacokinetics; poly(anhydride); poly(ethylene glycol) 2000