| Autor: |
Shadmani, Nasim, Makvandi, Pooyan, Parsa, Maliheh, Azadi, Amir, Nedaei, Keivan, Mozafari, Negin, Poursina, Narges, Mattoli, Virgilio, Tay, Franklin R., Maleki, Aziz, Hamidi, Mehrdad |
| Zdroj: |
Molecular Pharmaceutics; 20230101, Issue: Preprints |
| Abstrakt: |
The blood–brain barrier (BBB) acts as a physical/biochemical barrier that protects brain parenchyma from potential hazards exerted by different xenobiotics found in the systemic circulation. This barrier is created by “a lipophilic gate” as well as a series of highly organized influx/efflux mechanisms. The BBB bottleneck adversely affects the efficacy of chemotherapeutic agents in treating different CNS malignancies such as glioblastoma, an aggressive type of cancer affecting the brain. In the present study, mesoporous silica nanoparticles (MSNs) were conjugated with the transactivator of transcription (TAT) peptide, a cell-penetrating peptide, to produce MSN-NH-TAT with the aim of improving methotrexate (MTX) penetration into the brain. The TAT-modified nanosystem was characterized by Fourier transform infrared spectrometry (FTIR), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), and N2adsorption–desorption analysis. In vitrohemolysis and cell viability studies confirmed the biocompatibility of the MSN-based nanocarriers. In addition, in vivostudies showed that the MTX-loaded MSN-NH-TAT improved brain-to-plasma concentration ratio, brain uptake clearance, and the drug’s blood terminal half-life, compared with the use of free MTX. Taken together, the results of the present study indicate that MSN functionalization with TAT is crucial for delivery of MTX into the brain. The present nanosystem represents a promising alternative drug carrier to deliver MTX into the brain via overcoming the BBB. |
| Databáze: |
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