Aminoglycosides behavior in mesoporous silica-type delivery system Laura Bajenaru*, Silviu Nastase*, Cristian Matei*, Daniela S.

Iancu**, Cristian Bogdan Iancu**, Daniela Berger** * "Politehnica" University of Bucharest, Faculty of Applied Chemistry and Material Science, Romania

**National Institute of Legal Medicine, Genetics Laboratory, Romania

The benefits of aminoglycosides class in long terms therapeutics protocols are shaded by oto- and nephrotoxicity. Mesoporous silica-based drug delivery system can reduce the side-effects by controlling the release rate to a specific site of the body. This type of matrix displays no acute toxicity and, in order to optimize the drug adsorption and the delivery kinetic pattern, its textural features, like high surface area, pore volume, tunable pore size and acidity enhanced by aluminum content, are easily adaptable. We have studied the behavior of two related aminoglycosides, gentamicin, and kanamicin loaded on mesoporous silica-type supports, MCM41 and AlMCM41. Correlation between drug adsorption experiments data and release kinetic profiles, provided information regarding the drug-support

interaction mechanism. The obtained results revealed considerable differences between the analyzed drug molecules. Kanamicin presents a satisfactory adsorption ability and a slow release rate. Contrary, gentamicin reveals a weak adsorption tendency on mesoporous support and a low cumulative release after 24h. The loading experiments were performed in aqueous solutions and the drug uptake on the support was estimated by UV-VIS spectroscopy via a derivatization method using o-phthaldialdehyde. The presence of the aminoglycosides in hybrid materials was confirmed by FTIR spectroscopy. Cellular stress response that might occurred after exposure to mesoporous silica materials was evaluated based on gene expression changes. Oxidative stress was quantified through expression of GSTA2 (glutathione S-transferase alpha 2), endoplasmic reticulum stress through expression of HSPA5 (heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa)) and genotoxic stress through expression of TP53 (tumor protein p53). The results exhibit over-expression of GSTA2 and HSPA5 in AlMCM41 case and under-expression of TP53 in MCM41 case. The variations of expression profiles are illustrative for the mechanism of molecular action.

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