Alzheimer’s disease (AD) isthe most common form of dementia and has become one of the biggest globalhealthcare challenges. The pathophysiology of this disease is not fully understoodand there are no effective therapies to ameliorate this condition.
Prior researchhas demonstrated that progressive production and accumulation of insolubleprotein aggregates, such as neurofibrillary tangles of tau and amyloid-? (A?)plaques in the brain are supposed to trigger pathogenic cascades thateventually lead to AD, thus leading to brain atrophy and neurodegeneration. Recentstudies suggest that oxidative stress plays a crucial role on the pathophysiologyof the disease progression. The prevalence of Alzheimer’s disease is increasing especiallyin populations of people over 65.
The efficacy of treatment is still verylimited due to various factors including the blood brain barrier limitations andlack of deeper understanding of the neuropathology of AD. Liposomal techniqueshave long been utilized as a potent Drug Delivery System (DDS) to the brain,because the liposomal particles can encapsulate compounds and prevent rapidelimination or degradation. An encapsulated penetration through the BBB whichin turn increase the effective dose of a compound. The liposomal vesicles arenon-toxic, non-immunogenic (low allergenicity), non-carcinogenic andbiodegradable. An amyloid-beta A?clearance strategy in conjunction with decrease of the oxidative stress is anovel and promising pursuit as a promising disease modifying therapy to treatthe progression of AD. Prior in-vitro research has demonstrated that nanoliposomeswith curcumin, or the curcumin derivative, were able to inhibit the formation of(A?) plaques. Similar results were found in cases where the administration of quercetin liposomes and ?-Mangostein nanoliposomes.Both of these natural flavonoid compounds have shown to protect against neurodegenerationand facilitated A? clearance.
However, a combinatory approach of combining severalpotent natural compounds has not be evaluated earlier. The effect of various combinationsof nanoliposomes (a synergistic system containing curcumin, quercetin and ?-Mangosteincollectively in various dosages) on the oxidative stress and decrease A?aggregation was investigated and certain novel compound synergies wereidentified.A significant problem whenusing natural compounds as a therapeutic modality are limitations arising dueto hydrophobic nature, poor aqueous(water) solubility or insolubility incertain cases. This manifests as low bioavailability and low accumulation in braintissue or target organ.
A nasal delivery is a noninvasive delivery system, thatcan produce higher bioavailability than oral route due to the decrease hepaticmetabolism, shorter distance to brain target and easy penetration through thebrain and enhances pharmacokinetics of the compounds, thus solve the problem ofthe nutraceutical efficacy and also act as a novel system of delivering variousmolecules into brain in an efficient way