Romanian Society of Pharmaceutical Sciences

« Back to Farmacia Journal 5/2024

ENHANCED CYTOTOXICITY OF IRINOTECAN ADSORBED ON MESOSTRUCTURED ALUMINOSILICATE MATRICES

LUMINITA CLAUDIA MICLEA 1,2, SILVIU NASTASE 3, LAURA BAJENARU 3, RAUL AUGUSTIN MITRAN 4, CRISTIAN MATEI 3, FAWZIA SHA’AT 5, EUGEN RADU 6, MIHAELA G. MOISESCU 1, 2*, DANIELA BERGER3, TUDOR SAVOPOL 1,2

1 Biophysics and Cellular Biotechnology Dept., “Carol Davila” University of Medicine and Pharmacy, 050474, Bucharest, Romania
2 Excellence Centre for Research in Biophysics and Cellular Biotechnology, “Carol Davila” University of Medicine and Pharmacy, 050474, Bucharest, Romania
3 Faculty of Chemical Engineering and Biotechnologies, National University for Science and Technology Politehnica of Bucharest, 011061, Bucharest, Romania
4 “Ilie Murgulescu” Institute of Physical Chemistry, Romanian Academy, 060021, Bucharest, Romania
5 National Institute for Chemical - Pharmaceutical Research and Development - ICCF, 031299, Bucharest, Romania
6 Microbiology III Dept., “Carol Davila” University of Medicine and Pharmacy, 050098, Bucharest, Romania

Download Full Article PDF

Mesostructured silica, such as MCM-41 and SBA-15 and aluminosilicates have demonstrated good biocompatibility and are used as nanosized drug delivery systems (DDSs). Doping with aluminium modulates their physico-chemical properties. This study aimed to assess the metabolic impact of the 24 h or 48 h incubation of NIH3T3 murine fibroblastic cells with three categories of aluminium-doped MCM-41 and SBA-15 used as DDSs for the cytotoxic irinotecan. After 24 h, unloaded Al-doped DDSs at 90 μg/mL presented no toxic effects. Irinotecan release from DDSs followed a Fickian diffusion with various release profiles. Higher Al content led to higher residual drug amounts, while larger pore sizes resulted in faster desorption of irinotecan. Irinotecan loaded onto Al-doped DDSs decreased cell viability compared to irinotecan in solution. The MCM-based carriers demonstrated greater effectiveness in delivering irinotecan than SBA-based DDSs. The 48 h discontinuous exposure to irinotecan-loaded DDSs exhibited similar cytotoxicity to continuous exposure, suggesting a saturation of DDSs cellular uptake. Confocal microscopy revealed that DDSs were embedded in the cell membranes, supporting the hypothesis of an endocytosis-driven uptake. Our results showed that mesoporous aluminosilicates can augment intracellular irinotecan delivery as a Trojan horse.