With
the aging of the population, the incidence of Alzheimer's disease (AD)
has increased dramatically, causing severe medical, care, and economic
burdens on society and families. The efficacy of rivastigmine hydrogen
tartrate (RHT), the first-line clinical treatment, is severely limited
by the complex and multiple pathogenesis of AD and low brain
bioavailability caused by the blood-brain barrier (BBB). Confronting
such two bottlenecks, the development of multi-target agents
encapsulated BBB-bypassing drug delivery systems offer tremendous
therapeutics possibilities for AD. In this study, a tailored phytosomes
based nose-to-brain drug delivery system with appropriate plume was
successfully designed and developed. On the one hand, Ginseng RG3-based
phytosomes loaded with RHT was designed for the co-delivery of GRg3 and
RHT, achieving the multi-target pharmacology for AD treatment. On the
other hand, a tailored nose-to-brain drug delivery system was
established for the satisfactory nose-to-brain delivery efficiency,
avoiding the obstacle of BBB through bypassing it. In the
pharmacodynamic study based on AD rat model, GRg3@RHT exhibited
obviously synergic effect, effectively break the vicious cycle of AD
progression, ultimately markedly ameliorating learning and memory
ability as well as behavioral dysfunctions, and delaying the
neurodegenerative process associated with AD. In addition, the strong
correlation of viscosity-droplet size-plume geometry-olfactory
deposition was also established, and further proved by the in vivo
pharmacokinetic study, which is proposed to provide evidence to enhance
nose-to-brain delivery efficiency. This study is anticipated to provide
novel insights into AD treatment strategies while offering innovative
ideas for drug delivery approaches targeting nervous system disorders.
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