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  • Title: Methotrexate-loaded SLNs prepared by coacervation technique: in vitro cytotoxicity and in vivo pharmacokinetics and biodistribution.
    Author: Battaglia L, Serpe L, Muntoni E, Zara G, Trotta M, Gallarate M.
    Journal: Nanomedicine (Lond); 2011 Nov; 6(9):1561-73. PubMed ID: 22011315.
    Abstract:
    AIM: 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. MATERIALS & 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. CONCLUSION: 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.
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