Methotrexate-loaded SLNs prepared by coacervation technique: in vitro cytotoxicity and in vivo pharmacokinetics and biodistribution.
OBJECTIVE
Recently, 'coacervation' has been proposed as a new method to prepare fatty acid solid lipid nanoparticles (SLNs). The aim of this work was to encapsulate methotrexate, a hydrophilic anticancer drug, within SLNs obtained by coacervation, through hydrophobic ion pairing and to evaluate the potential efficacy in in vitro and in vivo breast tumor models of drug-loaded nanoparticles.


METHODS
Methotrexate-loaded SLN efficacy was evaluated in vitro towards MCF-7 and Mat B-III cell lines (human and murine breast tumor cell lines). Pharmacokinetics of drug-loaded nanoparticles was evaluated in male Wistar rats and biodistribution in a breast tumor model (Mat B-III) in female Fisher rats.


RESULTS
Drug-loaded SLNs showed an increased cytotoxicity towards MCF-7 and Mat B-III cell lines compared with free drug. After intravenous administration, drug plasmatic concentration was increased and a major drug accumulation within neoplastic tissue was shown when the drug was loaded in SLNs, compared with drug solution alone. Encapsulation of the drug within nanoparticles also increased its oral uptake after duodenal administration.


CONCLUSIONS
SLNs are promising vehicles for the delivery of methotrexate, since an increase of efficacy in vitro and a preferential accumulation in breast cancer in vivo were shown. Original submitted 29 October 2010; Revision submitted 19 March 2011.
Università degli Studi di Torino - Dipartimento di Scienza e Tecnologia del Farmaco - via Pietro Giuria 9, Torino, Italy.
Luigi
L
Battaglia
Loredana
L
Serpe
Elisabetta
E
Muntoni
GianPaolo
G
Zara
Michele
M
Trotta
Marina
M
Gallarate
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry*; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
D004337:Drug Carriers; D008055:Lipids; D008727:Methotrexate