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.