Title : Innovations in rivastigmine delivery: Nanostructured lipid carriers encapsulated in microneedles for enhanced transdermal delivery
Abstract:
Rivastigmine (RHT), used in the management of Alzheimer's disease, reduces acetylcholine degradation and enhances the cognitive function. Challenges in RHT delivery arise due to its limited ability to permeate the brain, short half-life, low bioavailability, and abdominal side effects. In an effort to address these challenges, we investigated the use of nanostructured lipid carriers (NLCs) for transdermal delivery of RHT. To enhance the efficacy of the transdermal delivery, microneedles (MNs) loaded with NLCs were also developed and characterized. The NLCs were prepared using the double emulsion method, incorporating Compritol ATO 888 as a solid lipid and tocopherol acetate as a liquid lipid. Different parameters were evaluated to optimize NLC properties, as solid lipid to liquid lipid ratio, sonication time, lipid phase concentration, and initial drug amount. The MNs were made-up using polyvinyl alcohol (PVA), at different concentrations, and the best MN formulation was subsequently loaded with the optimal NLCs dispersion. The optimal selected NLC formulations demonstrated a small size of ≤60 nm, with an entrapment efficiency reaching 53%. Additionally, the NLCs exhibited the capability to sustain RHT release for up to 7 hours. The optimal MNs, composed of 15% PVA, displayed good mechanical properties and insertion capability, and resulted in complete drug release within one hour and significant improvement in drug permeation. In summary, the successful development of MNs loaded with NLCs containing RHT highlights their capacity to release NLCs and enhance percutaneous permeation.