ENHANCED CYTOTOXICITY OF IRINOTECAN ADSORBED ON MESOSTRUCTURED ALUMINOSILICATE MATRICES

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 g/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. RezumatSilicea mezostructurat, cum ar fi MCM-41 i SBA-15, i aluminosilicaii prezint o bun biocompatibilitate i sunt utilizai ca sisteme dimensiuni nanometrice pentru livrarea medicamentelor (DDS).Dopajul cu aluminiu moduleaz proprietile fizicochimice ale acestora.Acest studiu a avut ca scop evaluarea impactului metabolic al incubrii timp de 24 sau 48 de ore a fibroblastelor de oarece NIH3T3 cu trei categorii de MCM-41 i SBA-15 dopate cu aluminiu utilizate ca DDS pentru citotoxicul irinotecan.Dup 24 de ore, DDS-urile dopate cu Al (90 g/mL) nu au prezentat efecte toxice.Eliberarea irinotecanului din DDS a urmat modelul difuziei Fick, cu diferite profiluri de eliberare.Coninutul mai mare de Al a dus la cantiti mai mari de medicament rezidual n DDS, n timp ce dimensiunile mai mari ale porilor au dus la desorbia mai rapid a irinotecanului.Irinotecanul ncrcat pe DDS dopat cu Al a sczut viabilitatea celular comparativ cu irinotecanul n soluie.DDS-urile bazate pe MCM au demonstrat o eficacitate mai mare dect cele bazate pe SBA n livrarea intracelular a irinotecanului.Expunerea discontinu de 48 de ore la DDS ncrcate cu irinotecan a prezentat citotoxicitate similar cu expunerea continu, sugernd o saturaie a captrii celulare a DDS-urilor.Microscopia confocal a localizat DDS-urile ncorporate n membranele celulare, susinnd un mecanism de ncorporare celular prin endocitoz.Rezultatele noastre au artat c aluminosilicaii mezoporoi pot fi folosii drept "cal troian" pentru a crete livrarea intracelular a irinotecanului.