Lipid-Coated MCM-41 Mesoporous Silica Nanoparticles Loaded with Berberine Improved Inhibition of Acetylcholine Esterase and Amyloid Formation

Abstract

Selective permeability of the blood–brain barrier limits effective treatment of neurodegenerative disorders. In the present study, brain-targeted lipid-coated mesoporous silica nanoparticles (MSNs) containing berberine (BBR) were synthesized for the effective treatment of Alzheimer’s disease (AD). The study involved synthesis of Mobil Composition of Matter-41 (MCM-41) mesoporous silica nanoparticles (MSNs), BBR loading, and lipid coating of MSNs (MSNs-BBR-L) and in vitro and in vivo characterization of MSNs-BBR-L. The liposomes (for lipid coating) were prepared by the thin-film hydration method. Transmission electron microscopy (TEM) images indicated 5 nm thickness of the lipid coating. Dynamic light scattering (DLS) and TEM results confirmed that the size of synthesized MSNs-BBR-L was in the range of 80–100 nm. The X-ray diffraction (XRD) pattern demonstrated retention of the ordered structure of BBR after encapsulation and lipid coating. Fourier transform infrared (FTIR) spectrum confirmed the formation of a lipid coat over the MSN particles. MSNs-BBR-L displayed significantly (p < 0.05) higher acetylcholine esterase (AChE) inhibitory activity. The study confirmed significant (p < 0.05) amyloid fibrillation inhibition and decreased the malondialdehyde (MDA) level by MSNs-BBR-L. Pure BBR- and MSNs-BBR-L-treated AD animals showed a significant decrease in the BACE-1 level compared to scopolamine-intoxicated mice. Eight times higher area under the curve for MSNs-BBR-L (2400 ± 27.44 ng h/mL) was recorded compared to the pure BBR (295.5 ± 0.755 ng h/mL). Overall, these results highlight the utility of MSNs-BBR-L as promising drug delivery vehicles for brain delivery of drugs.

Multifunctional Mesoporous Silica Nanoparticles for Oral Drug Delivery

“…Taken together, our findings indicate that fine-tuning the geometry of nanoparticles may influence their biological fate, such as increased cellular uptake and oral bioavailability [23]. Lipid-coated nanoparticles are found to be effective in overcoming epithelial barriers [40]. The particle absorption takes place due to their strong interaction with cell lipid bilayers.…”

“…It is mainly used to protect the drug from various hydrolytic enzymes, improve residence time, increase the absorption as well as the bioavailability. Various nanocarriers for oral drug delivery include polymeric nanocarriers, inorganic nanocarriers, solid lipids as nanocarriers, mesoporous silica nanoparticles, and metallic nanoparticles [4,17,30,32,34,37,40,52,62,64,83]. Silica based nano carriers for delivery of drugs, biomolecules, and food are an emerging highlight.…”

“…Positively charged constituent parts have been shown to have an advanced endocytosis rate than a negatively charged constituent. Therefore, the ability of a negatively charged constituent Lipid-coated nanoparticles are found to be effective in overcoming epithelial barriers [40]. The particle absorption takes place due to their strong interaction with cell lipid bilayers.…”

The Effect of Oxidative Stress and Memantine-Incorporated Reactive Oxygen Species-Sensitive Nanoparticles on the Expression of N-Methyl-d-aspartate Receptor Subunit 1 in Brain Cancer Cells for Alzheimer’s Disease Application

“…The physiological state of the brain is quite different to that of other organs because the BBB is a primary obstacle for drug delivery to the brain [25,26]. For this reason, various delivery platforms have been investigated to improve the penetration and/or transport of bioactive agents [26][27][28][29][30][31][32][33][34][35][36][41][42][43][44][45][46][47]. For example, surfactants such as polysorbate 80 have been used to allow nanoparticles or drug carriers to penetrate the BBB [41][42][43][44][45][46].…”

“…They showed that nanocomposites significantly increased the level of adenosine phosphate, reduced the oxidative stress and reversed dopaminergic neuronal damage. Berberine-encapsulated mesoporous silica nanoparticles effectively inhibited amyloid fibrillation and decreased the level of malondialdehyde [36]. Lee et al reported that redox-responsive nanoparticles have sensitivity to ROS formation in cancer cells and that the release rate of anticancer drugs can be controlled by intracellular oxidative stress in cancer cells [37].…”