Antitumoral drug loaded in TEOS nanoparticles
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Antitumoral drug loaded in TEOS nanoparticles Ana Paula V. Araújo1; Claure N. Lunardi1, Anderson J. Gomes1 1 University of Brasília - Faculdade de Ceilândia (UnB-FCE), Brasília, DF 7220-140, Brasil ABSTRACT Methotrexate (MTX), is a potent immunomodulating drug and widely used in the treatment of cancer, psoriasis and others disease. Despite its efficacy, the use of MTX is greatly limited due to its toxicity. To solve this problem, we prepared nanoparticles of tetraethyl orthosilicate (NPTEOS) containing the compound methotrexate (MTX), by the sol-gel method. This drug delivery system (DDS) showed a loading efficiency of 39.7%. Size distribution studies were performed with dynamic light scattering and scanning electron microscopy revealing that these particles were spherical in shape, with a mean diameter between 140-430 nm and a low polydispersity (0.12 – 0.26). Also the particles displayed a low tendency toward aggregation which was confirmed by the low zeta potential -61.4 mV. Profile release showed a slow release loaded with MTX (PBS buffer pH = 7.4). The slow release can be attributed to the low porosity of the NPTEOS and the extremely low diffusivity of MTX in aqueous media. B16-F10 cells were used to assay the toxicity and uptake of NP-TEOS showing to be nontoxic without MTX making a good candidate for DDS. INTRODUCTION Recently, silica nanoparticles (NPs) have been intensively studied for their potential applications as drug delivery system [1, 2]. This system has several advantages including non-acute toxicity, biocompatible and biochemically inert. Also, its simplicity of preparation, by reaction from relatively inexpensive precursor molecules such as tetraethyl orthosilicate (TEOS) (Figure 1), methyl orthosilicate , polydimethylsiloxane and others [3],make theses nanoparticles unique with uniform mesopores which enable loading of large amounts of various chemical drugs [4]. The uniform small size allow easy uptake by lysosomes in cancer cells which size varies from 0.1 to 1.2 Pm [5, 6]. Besides the size, another important aspect is its relation to pH dependence value between 4.8 and 6.4, substantially less than that of cytosol (pH = 7.4), which may be very favorable to drug release from a nanovalve system [2]. This type of DDS would ensure that the entrapped drug would be released from the nanoparticle only after the nanoparticle has been endocytosed into the target tissue [7]. MTX (Figure 1) is used to treat choriocarcinoma, leukemia in the spinal fluid, osteosarcoma, breast cancer, lung cancer, non-Hodgkin lymphoma, and head and neck cancers. It is also used to treat other cancers and non-cancerous conditions [8-10].This drug is also part of a general group of chemotherapy drugs known as anti-metabolites. It prevents cells from using folate to make DNA and RNA. Because cancer cells need these substances to make new cells, methotrexate helps to stop the growth of cancer cells. Despite its efficacy, the use of MTX is greatly limited due to its toxicity to normal cells, drug resistance, nephrotoxicity, bone
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