Tamoxifen/montmorillonite as a controlled release oral system

• Published in: Journal of drug delivery science and technology 2023-08, Vol.85, p.104572, Article 104572
• Main Authors: Silva, Dayanne Tomaz Casimiro, Arruda, Igor Eduardo Silva, Araújo, José Izak Ribeiro de, França, Denise de Brito, Damasceno, Bolivar Ponciano Goulart de Lima, Oliveira, Fátima de Cássia Evangelista de, Pessoa, Cláudia, Soares, Mônica Felts de La Roca, Fonseca, Maria Gardênnia, Soares-Sobrinho, José Lamartine
• Format: Article
• Language: English
• Subjects: Controlled release; Drug delivery system; Montmorillonite; Tamoxifen
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2023.104572

Drugs have been incorporated into clay minerals to obtain a controlled-release system. In the present study, tamoxifen citrate (TMX) was loaded in pharmaceutical montmorillonite (VHS) at pH 3.0, 4.0, and 5.0 and released in vitro under simulated stomach and intestinal conditions to evaluate the cytotoxic activity of TMX/VHS systems. The systems were characterized using structural (X-ray diffractometry and Fourier transform infrared spectroscopy) and thermal (thermogravimetric analysis and differential calorimetry) techniques. TMX was loaded in VHS via a reaction between 1660 mg L−1 TMX methanol solutions and 0.1 g of VHS at pH 3.0 (VHS/TMX/pH3), 4.0 (VHS/TMX/pH4), and 5.0 (VHS/TMX/pH5) for 12 h at 200 rpm and 25 °C. The release of TMX was evaluated with dispersed amounts of loaded TMX systems in a simulated medium at pH 1.2 and 6.8, and TXM was quantified by high-performance liquid chromatography. Cytotoxicity tests were performed in vitro using the MTT assay for human tumor cell lineages. Characterization results indicated the intercalation of TMX in the clay mineral, and the amounts of TMX were 344.7, 347.1, and 374.4 mg per gram of VHS for the systems prepared at pH 3, 4, and 5, respectively. Releases of 8.40% (VHS/TMX/pH3), 8.68% (VHS/TMX/pH4), and 11.15% (VHS/TMX/pH5) occurred at pH 1.2, whereas at pH 6.8, the release of TMX increased to 21.21% (VHS/TMX/pH3), 24.85% (VHS/TMX/pH4), and 39.27% (VHS/TMX/pH5). The VHS/TMX systems exhibited cytotoxicity with increasing concentrations for all cells, with increased cytotoxic activity with IC50 of 54.57 μg mL−1 (TMX 20.10 μg mL−1) for the VHS/TMX/pH5 for glioblastoma lineages. Therefore, the TMX/VHS systems presented drug release control and, depending on the concentration, could exert cytotoxic activity without causing damage to normal cells, thus reducing adverse effects. [Display omitted] •Hybrids formed from the clay mineral Montmorillonite and the anticancer drug tamoxifen citrate.•The release of the drug from the interior of the clay is influenced by its interaction with the clay surface.•The hybrid with the lowest affinity with the clay surface obtained greater release and better cytotoxic activity.•The hybrid with that had less interaction with the clay surface, showed cytotoxicity without causing damage to normal cells.