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.

Gingerol is a major dietary compound that occurs in several plants belonging to the Zingiberaceae family. In the current study, the protective effect of gingerol on STZ-induced sporadic Alzheimer’s disease (SAD) was determined. Gingerol was isolated from the seeds of Aframomum melegueta K. Schum and tested at doses of 10 and 20 mg/kgbwt for its possible effect on the SAD model in mice, using celecoxib (30 mg/kg bwt) as a reference standard. The curative effects of gingerol were assessed through measurement of β-amyloid (Aβ-42), α-, β- secretases, APH1a and COX-2 levels. In addition, improvement in the cognitive deficit in mice after treatment was confirmed using the water maze and Y-maze with intra-maze cues. Gingerol improved the cognitive and behavioral impairment and AD-like pathology in streptozotocin model mice. These beneficial effects occurred with an increase in α-secretase activity and a decrease in cerebral Aβ-42, β- secretase, APH1a activity and COX-2-linked neuro-inflammation.

Three-dimensional (3D) bioprinting is a novel technique applied to manufacture semisolid or solid objects via deposition of successive thin layers. The widespread implementation of the 3D bioprinting technology encouraged scientists to evaluate its feasibility for applications in human regenerative medicine. 3D bioprinting gained much interest as a new strategy to prepare implantable 3D tissues or organs, tissue and organ evaluation models to test drugs, and cell/material interaction systems. The present work summarizes recent and relevant progress based on the use of hydrogels for the technology of 3D bioprinting and their emerging biomedical applications. An overview of different 3D printing techniques in addition to the nature and properties of bioinks used will be described with a focus on hydrogels as suitable bioinks for 3D printing. A comprehensive overview of triblock copolymers with emphasis on Pluronic F127 (PF127) as a bioink in 3D printing for regenerative medicine will be provided. Several biomedical applications of PF127 in tissue engineering, particularly in bone and cartilage regeneration and in vascular reconstruction, will be also discussed. Impact statement: The current review highlights the use of three-dimensional (3D) bioprinting for regenerative medicine, stressing the manipulation of hydrogels as the most commonly used bioinks. The advantages and shortcomings of using hydrogels for 3D printing procedures are discussed with a particular focus on triblock copolymers and Pluronics. A brief overview of applying bioink Pluronic F127 in applications of 3D bioprinting for tissue reconstruction is also provided.