Design of magnetic/mesoporous silica nanocomposites as a delivery platform of antineoplastic drugs

The application of mesoporous silica materials as carriers in the drug delivery systems is a promising and new approach in nanomedicine. Mesoporous silicates are characterized by narrow distribution of pores with a controlled... [ view full abstract ]

The application of mesoporous silica materials as carriers in the drug delivery systems is a promising and new approach in nanomedicine. Mesoporous silicates are characterized by narrow distribution of pores with a controlled size, large pore volume, high surface area, dual-functional surface (external and internal) and good chemical and thermal stability. New perspective in targeted delivery of antineoplastic drugs is given by mesoporous silicas integrated with magnetic nanoparticles. These composites allow selective supply of the drug to the targeted organ of the body when an external magnetic field is applied. The preparation of appropriate delivery systems based on these materials can solve some problems such as low concentration in the region of interest and toxic side effects of antineoplastic drugs.

Mitoxantrone is a synthetic antineoplastic drug, widely used as a chemotherapeutic agent in the treatment of various types of cancer.  Glucocorticoids, i.e. prednisolone, have been used in clinical oncology for more than three decades because of their anti-inflammatory action that additionally influences the oncological therapy.

In the present study we developed dual delivery system of mitoxantron/prednisolone on the basis of magnetic/mesoporous silica nanocomposite carriers.   

Magnetic/mesoporous silica nanocomposites were synthesized and modified by post-synthesis method with –SO₃H groups (Scheme 1). Mitoxantrone was loaded by incipient wetness impregnation on the mesoporous support (Scheme 1). The functionalized and drug loaded formulations were characterized by powder XRD, N₂ physisorption, TEM, TG analysis, ATR-FT-IR and Mössbauer spectroscopy. The results from TG and N₂ physisorption measurments show that mitoxantrone was successfully loaded in the pores of the carrier. Additionally, coating by polyelectrolyte complex containing two layers, chitosan:prednisolone and sodium alginate, resulted in controlled release of loaded drug molecules (Scheme 1). The cytotoxicity of free and formulated mitoxantrone and prednisolone was evaluated using MTT-dye reduction assay in a panel of human tumor cell lines (HL-60/Dox (acute promyelocyte leukemia), K-562 (chronic myeloid leukemia), HD-MY-Z (Hodgkin lymphoma) and EJ (bladder carcinoma). The results obtained showed that encapsulated drugs evoked prominent concentration-dependent cytotoxic effects even at low tested concentrations.

Acknowledgements: Financial support from the Bulgarian-Hungarian Inter-Academic Exchange Agreement and the National Science Fund of Bulgaria (Grant DH 09/18) is acknowledged.