Introduction

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by progressive memory loss, cognitive decline, and behavioral disturbances. Pathological hallmarks include amyloid-β deposition, tau hyperphosphorylation, and oxidative stress. Rivastigmine tartrate, a cholinesterase inhibitor approved for AD management, is typically administered orally but suffers from poor bioavailability due to extensive first-pass metabolism and is further associated with adverse cardiovascular and gastrointestinal effects. To address these limitations, the present study explored the development of an intranasal nanocarrier-based formulation of rivastigmine tartrate using multi-walled carbon nanotubes (MWCNTs) functionalized with carboxyl and polyethylene glycol (MWCNT-COOH-PEG).

Methods

Intranasal administration was chosen to bypass the blood–brain barrier, enable direct nose-to-brain transport, and reduce systemic side effects. Functionalized MWCNTs were selected as drug carriers for their high surface area, biocompatibility, and reported neuroprotective potential. The formulation was optimized using a 3² factorial design. Preformulation assessments, including Fourier-transform infrared spectroscopy and differential scanning calorimetry, confirmed drug–excipient compatibility. Critical formulation parameters such as particle size, zeta potential, and entrapment efficiency were studied. In vitro release testing and ex vivo permeation studies using goat nasal mucosa were conducted. Stability studies were performed to evaluate formulation robustness, while in vivo pharmacokinetic and biodistribution assessments were carried out using male Wistar rats.

Results

The optimized intranasal formulation exhibited favorable particle size distribution, surface charge stability, and high drug entrapment efficiency. In vitro release studies revealed a sustained drug release pattern. Ex vivo permeation results demonstrated 56% cumulative drug release at 12 hours and 65.55% at 24 hours across goat nasal mucosa, confirming controlled and prolonged diffusion. Stability studies validated the physical and chemical stability of the formulation. Pharmacokinetic and biodistribution studies indicated improved brain uptake of rivastigmine tartrate compared to conventional administration routes.

Conclusion

The study demonstrated that intranasal delivery of rivastigmine tartrate-loaded MWCNT-COOH-PEG nanocarriers is a promising alternative to conventional oral therapy for Alzheimer’s disease.