Awad, R. | bioRxiv Science

bioRxiv2025

Nose-to-Brain Administration of Cannabidiol-Loaded Polymeric Micelles Improves the Core Behavioral Symptoms of Autism Spectrum Disorder

Neurodevelopmental disorders including autism spectrum disorder (ASD) affect 5.9% of the global population. Research shows the potential therapeutic use of cannabidiol (CBD) to treat different neurodevelopmental disorders, including ASD. Intranasal drug delivery (i.n.) is a non-invasive and painless administration route that enhances drug bioavailability in the brain by bypassing the blood-brain barrier. However, i.n. has limited bioavailability due to the low nasal mucosa permeability. Various polymeric nanoparticles have been investigated for i.n. delivery with different successes. In this study, we developed and characterized polymeric micelles of the poly(ethylene oxide)-b-poly(propylene oxide) block copolymer Pluronic(R) F127 loaded with 25% w/w CBD for nose-to-brain delivery in ASD. CBD-loaded polymeric micelles display a hydrodynamic diameter of 41 {+/-} 1 nm by Intensity and 23 {+/-} 1 nm by Number, as measured by dynamic light scattering, and showed very good compatibility and permeability in the human nasal septum cell line RPMI 2650, an in vitro model of the nasal epithelium. The accumulation of CBD-loaded polymeric micelles upon i.n. administration to autistic rats is confirmed by bioimaging. The pharmacokinetics of CBD upon i.n. (dose of 5 mg/kg) and oral (15 mg/kg) administration of the loaded polymeric micelles shows a 27.8% increase of the CBD concentration in the brain 20 min of autistic rats after i.n. administration, despite the 3-fold decrease in the dose. Finally, the efficacy of this nanoformulation to improve the core symptoms of ASD is demonstrated in behavioral studies in a rat model of the disorder.

neuroscience↗

bioRxiv2023

Performing Roux-N Y Gastric Bypass on Rabbits: Perspective Report to Evaluate Body Weight Changes Food Consumption, And the Malabsorption of Vitamin D3

In 1998, Dr. Scopinaro published the first-ever known bariatric surgery, followed by reports by Buchwald and Oien in 2003 and 2013 [1,2]. Bariatric surgery (BS) is the most effective therapy against obesity, and recently it was recommended for type 2 diabetes as a therapeutic plan [3]. BS includes; Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy, and laparoscopic adjustable gastric banding has gained the attention of most healthcare providers in elevation of the issue of obesity for its ease and fast results, especially with patients with mobility problems and those with high risk to develop chronic diseases [1,2]. Gastric bypass is considered the most common BS and a gold standard for weight loss, also known as Roux-en-Y gastric bypass (RYGB). The procedure of this BS is by creating a small pouch of the stomach (300 mL capacity) connected directly to the jejunum by bypassing the duodenum. RYGB has many advantages, such as; the alteration of guts hormones, which reduces appetite and hunger feeling, increases energy expenditure, causes significant long-term weight loss (60-80% of the excess body weight), decreases the amount of food consumed, and preserves 50% of the weight loss during this procedure. However, RYGB has some disadvantages. The most critical issue regarding this BS is altering the absorption of many medicines and nutrients, such as; vitamin D3 (Vit D3) [4,5]. (American Society for Metabolic and Bariatric Surgery. Bariatric Surgery Procedures. https://asmbs.org/patients/bariatric-surgery-procedures (accessed Feb 15, 2020). RYGB was performed on rodents before [6] but was never applied to rabbits. To determine the malabsorption procedure after the RYGB, the pharmacokinetics of the substance must be attained, and data must be calculated, such as; Cmax and Tmax, to determine the absorption mutation. It was reported that pharmacokinetic studies on rodents could not be accurate due to the erratic absorption of the rodents [7]; thus, many studies have suggested using larger animals, such as rabbits, that do not address the same problem [8]. The current study investigates the ability to perform RYGB on rabbits and tests the effect of the surgery on body weight, food consumption, and the absorption of Vit D3.

pharmacology and toxicology↗