Lea Koceva

Nose-to-brain drug delivery represents a promising non-invasive strategy for improving CNS targeting. However, conventional liquid formulations are limited by rapid mucociliary clearance and short mucosal residence time. This study developed a thermoresponsive in situ gel incorporating indocyanine green (ICG)-loaded nanoliposomes and evaluated its potential to enhance and modulate the ICG-associated brain distribution after intranasal administration of the formulation. ICG-loaded nanoliposomes were prepared using a modified thin-film hydration method and incorporated into a poloxamer-based gel containing hyaluronic acid and Carbomer 940 as mucoadhesive components. The nanoliposomes exhibited a mean particle size of 124 ± 3.25 nm, a unimodal size distribution, and a high ICG encapsulation efficiency of 93.33%. Rheological analysis confirmed a temperature-triggered sol-to-gel transition at the physiological nasal temperature (~32 °C), shear-thinning behavior, and rapid structural recovery suitable for intranasal application. Ex vivo fluorescence imaging in rats demonstrated distinct biodistribution profiles for the ICG-associated signal delivered via the liquid nanoliposomes and gel-incorporated nanoliposomes. Although the liquid liposomes showed faster early signal at 4 h, the gel formulation produced stronger and more sustained brain fluorescence at later time points. At 8 h and 24 h, whole-brain fluorescence was approximately twofold higher with the gel formulation than with the liquid liposomes formulation. These findings indicate that this thermoresponsive gel enhances nasal retention and may modulate the delivery profile of the nose-to-brain transport, supporting its potential as a platform for CNS-targeted delivery and the development of more effective therapies for neurodegenerative diseases.

Increasing environmental contamination with microplastics (MPs) raises significant concerns regarding their potential impact on reproductive health. This study evaluated the effects of prolonged oral exposure to fluorescent polystyrene microplastics (FPS-MPs) of different sizes on the male reproductive system in Wistar rats. Juvenile male rats at 21 days of age were exposed to FPS-MPs of 1 µm and 5 µm for 52 days, covering the period of sexual maturation and a complete spermatogenesis cycle. Body weight, reproductive organ indices, serum levels of testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), as well as sperm motility and morphology, were assessed. Reproductive potential and accumulation of microplastics in reproductive tissues were also evaluated. No significant differences were observed in body weight or most reproductive organ indices, except for a slight reduction in the left epididymis index in the group exposed to 5 µm particles. FPS-MPs induced size-dependent changes in the hormonal profile, including decreases in T and E2 and compensatory increases in FSH and LH, as well as impairments in sperm quality, which were more pronounced in rats exposed to smaller particles. In conclusion, fertility potential remained preserved, while FPS-MPs accumulated in the testes and epididymides, demonstrating subclinical, size-dependent effects on the male reproductive system.

This study aims to assess the rate and duration of rat brain retention after a single intranasal administration of indocyanine green (ICG) as an aqueous solution or encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles. Near-infrared fluorescence emission of ICG from the brain and visceral organs was measured at 1, 4, and 24 h, as well as at 1 and 2 weeks after administration. It was observed that both ICG formulations stained the olfactory bulbs and brainstem, the latter mainly in the basolateral region of the pons. Reduced staining was observed on day 7 after treatment, and the signal remains detectable on day 14. Additionally, while emission from ICG-labeled brains in water decreased after two weeks compared to day 7, in ICG-loaded nanoparticles, the emission was significantly higher on day 14. It is concluded that ICG is transported into the brain via both nose-to-brain delivery pathways—through and along olfactory or trigeminal nerves—and that ICG is a useful dye for in vivo studies due to its long-lasting emission and low toxicity. Furthermore, the suggested penetration of ICG-encapsulated PLGA nanoparticles via these transport mechanisms makes them a useful carrier for brain delivery of substances that are rapidly eliminated from circulation or do not cross the blood–brain barrier.