Polysorbate-coated mesoporous silica nanoparticles as an efficient carrier for improved rivastigmine brain delivery

• Published in: Brain research Vol. 1781; p. 147786
• Main Authors: Fateh Basharzad, Samaneh, Hamidi, Mehrdad, Maleki, Aziz, Karami, Zahra, Mohamadpour, Hamed, Reza Saghatchi Zanjani, Mohammad
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.04.2022
• Subjects: Alzheimer’s disease; Animals; Blood-brain barrier; Brain; Central nervous system; Drug Carriers - chemistry; Drug delivery; Drug Delivery Systems - methods; Mesoporous silica; Nanoparticles - chemistry; Pharmacokinetics; Polysorbates; Porosity; Rats; Rivastigmine; Silicon Dioxide - chemistry; Spectroscopy, Fourier Transform Infrared; Drug delivery; Alzheimer’s disease; Blood-brain barrier; Pharmacokinetics; Mesoporous silica; Central nervous system
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2022.147786

[Display omitted] •A calcium-doped mesoporous silica functionalized with polysorbate-80 as a targeting ligand introduce to achieve efficient delivery of rivastigmine into the Brain.•The developed drug delivery system was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, Zeta potential, and N2-adsorption–desorption analysis.•The nanosystem showed good biocompatibility with blood and the Brain cells.•Neuropharmacokinetic studies exhibited that the brain uptake clearance of the drug-loaded nanoparticles was significantly higher than that of the free drug. Targeted delivery of neurological therapeutic to the brain has been attracting more and more attention to the treatment of central nervous system (CNS) diseases. Nonetheless, the main obstacle in this road map is the existence of a blood–brain barrier (BBB) which limits the penetration efficiency of most CNS drugs into the brain parenchyma. This present investigation describes a facile synthetic strategy to prepare a highly biocompatible calcium-doped mesoporous silica nanoparticles (MSNs) functionalized by polysorbate-80 (PS) as targeting ligand to deliver rivastigmine (RV) into the brain via crossing the BBB. The developed nanosystem was characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), Zeta potential, and N2-adsorption–desorption analysis. In vitro hemolysis studies were carried out to confirm the biocompatibility of the nanocarriers. Our in vivo studies in an animal model of rats showed that the RV-loaded nanosystem was able to enhance the brain-to-plasma concentration ratio, brain uptake clearance, and plasma elimination half-life of the drug compared to the free one drug following intravenous (IV) administration. The results revealed that functionalization of MSNs by PS is crucial to deliver RV into the brain, suggesting PS-functionalized MSNs could be an effective carrier to deliver RV to the brain while overcoming BBB.