Enhancing Methotrexate Delivery in the Brain by Mesoporous Silica Nanoparticles Functionalized with Cell-Penetrating Peptide using in Vivo and ex Vivo Monitoring

Abstract

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 N2 adsorption–desorption analysis. In vitro hemolysis and cell viability studies confirmed the biocompatibility of the MSN-based nanocarriers. In addition, in vivo studies 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.

Voices in Molecular Pharmaceutics: Meet Dr. Nasim Shadmani Who Utilizes Cell Penetrating Peptides and Nanoparticles for Targeting Hard-to-Reach Areas of the Body Including the Brain

“…Also, new drug delivery approaches will be further implemented including silica-based nanoparticles, antibody drug conjugates, lipid nanoparticles, and gene therapy. 4 Thus, the main topics in pharmaceutical science research and education will be the selection of appropriate biomarkers and primers for diagnosis, improving compliance, optimizing dosages, and improving formulations. Permeability, delivery, bioavailability, and stability will be enhanced by using these advanced technologies.…”

“…The use of drug-based immunology, oncology treatments, and RNA-mediated interference will emerge in global markets. Also, new drug delivery approaches will be further implemented including silica-based nanoparticles, antibody drug conjugates, lipid nanoparticles, and gene therapy . Thus, the main topics in pharmaceutical science research and education will be the selection of appropriate biomarkers and primers for diagnosis, improving compliance, optimizing dosages, and improving formulations.…”

Peptide‐conjugated Nanoparticle Platforms for Targeted Delivery, Imaging, and Biosensing Applications

“…Furthermore, the labile ester bond in the prodrug released free drug in the tumor environment leading to the inhibition of the growth of the tumors. In different studies, CPPs were conjugated to mesoporous silica NPs, [60] polymer NPs,, [61–63] gold nanorods, [64] hepatitis B virus‐like NPs,, [65] and silver NPs [66] for drug delivery applications. The use of targeting and cell penetrating peptides together with NP formulations in different biomedical applications were discussed in some other recent reviews in details, and we refer the readers to these papers [67–69] …”

The synthesis and development of poly(ε-caprolactone) conjugated polyoxyethylene sorbitan oleate-based micelles for curcumin drug release: an in vitro study on breast cancer cells

“…The IC50 of PCL-T-M measurements were 278.30 and 236.19 mg mL −1 , respectively, and PCL-T-M did not show toxic traces. [57][58][59] The heatmap of concentration of Curloaded PCL-T-M, free Cur, and free PCL-T-M show using color changes from red (low intensity) to violet (high intensity), respectively (Fig. 8D and F).…”