Title : A Glimmer of hope from insulin NPs in vitro and ex vivo studies for the successful insulin delivery to the brain
Drug delivery to the brain is still forming the major drawback facing the successful management of neurodegenerative disorders, counting Alzheimer’s disease (AD) that represents most dementia cases in the elderly population worldwide. Nasal application with the aim of direct nose-to-brain delivery grants the drug molecules the ability to avoid the blood-brain barrier (BBB), which forms the primary obstacle facing effective brain delivery. The novel nanotechnologies are expected to develop innovative targeted drug-delivery systems. Solid lipid nanoparticles (SLNs) and polylactic-co-glycolic acid nanoparticles (PLGA NPs) presented themselves as competitive nanosystems for the brain delivery of therapeutics following the intranasal route. Insufficient brain insulin has been involved in AD progress, and the intranasal insulin for this purpose demonstrated promising results. In this research work, insulin was formulated into SLNs and PLGA NPs forms and chitosan-coated SLNs and PLGA NPs. The nanoformulations stability was assessed, then the in vitro and ex-vivo comparisons between the native insulin and insulin NPs were further investigated. Physiochemical results spotted the stability of encapsulated insulin in both the nanoformulations and the compatibility between the used materials. The in vitro results showed the superiority of nanoparticles in enhancing insulin dissolution, mucoadhesion, and permeation behavior and a positive role of chitosan-coating in the further enhancement. Moreover, ex-vivo investigations confirmed the in vitro results and showed the positive part of these nanosystems. Thus, incorporating insulin into chitosan-coated NPs holds excellent hope for successfully delivering insulin to the brain.