Novel Luteolin-Loaded Chitosan Decorated Nanoparticles for Brain-Targeting Delivery in a Sporadic Alzheimer’s Disease Mouse Model: Focus on Antioxidant, Anti-Inflammatory, and Amyloidogenic Pathways

Abstract

Preparation and evaluation of a non-invasive intranasal luteolin delivery for the management of cognitive dysfunction in Alzheimer’s disease (AD) using novel chitosan decorated nanoparticles. Development of luteolin-loaded chitosomes was followed by full in vitro characterization. In vivo efficacy was evaluated using a sporadic Alzheimer’s disease (SAD) animal model via intracerebroventricular injection of 3 mg/kg streptozotocin (ICV-STZ). Treatment groups of luteolin suspension and chitosomes (50 mg/kg) were then intranasally administered after 5 h of ICV-STZ followed by everyday administration for 21 consecutive days. Behavioral, histological, immunohistochemical, and biochemical studies were conducted. Chitosomes yielded promising quality attributes in terms of particle size (PS) (412.8 ± 3.28 nm), polydispersity index (PDI) (0.378 ± 0.07), Zeta potential (ZP) (37.4 ± 2.13 mv), and percentage entrapment efficiency (EE%) (86.6 ± 2.05%). Behavioral findings showed obvious improvement in the acquisition of short-term and long-term spatial memory. Furthermore, histological evaluation revealed an increased neuronal survival rate with a reduction in the number of amyloid plaques. Biochemical results showed improved antioxidant effects and reduced pro-inflammatory mediators’ levels. In addition, a suppression by half was observed in the levels of both Aβ aggregation and hyperphosphorylated-tau protein in comparison to the model control group which in turn confirmed the capability of luteolin-loaded chitosomes (LUT-CHS) in attenuating the pathological changes of AD. The prepared nanoparticles are considered a promising safe, effective, and non-invasive nanodelivery system that improves cognitive function in SAD albino mice as opposed to luteolin suspension.

Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes

“…Cs and its derivatives are successfully used as a liposome shell for drug delivery through the mucous membranes of the nose [36], eyes [37], mouth [38], and digestive system [39]. Cs can interact with negatively charged fragments, mainly with sialic acid in the mucous layers, due to its positively charged amino groups [40]. The mucoadhesive property of Cs is associated with the penetration of the polymer into glycoprotein mucin chains and the formation of tangles with mucus.…”

Exploring the Potential of Intranasally Administered Naturally Occurring Quercetin Loaded into Polymeric Nanocapsules as a Novel Platform for the Treatment of Anxiety

“…Our prepared formulation as well as QRC dispersion demonstrated no signs of nasal irritation when administered intranasally compared to when saline was administered intranasally. Based on these observations, both QRC loaded polymeric nanocapsules as well as QRC dispersion in the no irritation level on the nasal mucosa irritation index indicating that both are cilio-friendly [24]. To further validate the safety of our chosen formula, histopathological examination was conducted to analyze the rats' mucosa when the rats received either saline, benzalkonium chloride, or the chosen formula.…”

“…During nasal administration conducted in animal studies, an observational nasal irritation test was conducted [24]. Visual observation was conducted when saline, QRC dispersion, and QRC loaded polymeric nanocapsules were administered intranasally.…”

Phytonanoparticles for the treatment of Alzheimer’s disease: A review

“…All over the LUT-CHS reduced, the Aβ aggregation in brain of sporadic AD mouse. This suggested that the nanodrug delivery system with LUT-CHS is neuroprotective and safe with non-invasive drug administration (Abbas et al, 2022).…”