Folate-Targeted Nanoparticles Based on Albumin and Albumin/Alginate Mixtures as Controlled Release Systems of Tamoxifen: Synthesis and In Vitro Characterization

BSTRACT Purpose Preparation and in vitro characterization of tamoxifen (TMX)-loaded folate-targeted nanoparticles based on disulfide bond reduced bovine serum albumin (BSA-SH) and BSA-SH/alginate-cysteine (BSA-SH/ALG-CYS) mixtures as drug delivery systems. Methods Folate-nanoparticles were characterized in terms of folate content, morphology, size, zeta potential, TMX load and drug release kinetics. Additionally, cell viability and cellular uptake of nanoparticles were determined using different cancer cell lines. Results Folic acid (FOL) was successfully attached to nanoparticles (ranging between 79 and170 μmol folate/g NP). Nanoparticles with 76–417 nm mean size were obtained and loaded with TMX (4.2–7.7 μg/mg NP). Zeta potential and drug extraction revealed major superficial placement of the drug, especially in the case of BSA/ALG-FOL systems. Drug release studies in the presence of surfactant showed a gradual release of the drug between 4–7 h. In general, low cytotoxicity of unloaded systems was found. Internalization of the systems was achieved and mediated by folate receptor, especially in the case of BSA NP-FOL. The administration of 10 μM TMX by TMX-FOL NP showed their efficacy as controlled TMX release systems. Conclusions Promising anticancer action of these new TMX-loaded folate-targeted systems was demonstrated, allowing a new administration route to be studied in further in vivo studies in order to improve current TMX therapy.