Retinal pharmacodynamic and pharmacokinetic profile of cannabidiol in an in vivo model of retinal excitotoxicity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F25%3A43921489" target="_blank" >RIV/00023752:_____/25:43921489 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60461373:22330/25:43932713

Výsledek na webu

<a href="https://doi.org/10.1016/j.ejphar.2025.177323" target="_blank" >https://doi.org/10.1016/j.ejphar.2025.177323</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejphar.2025.177323" target="_blank" >10.1016/j.ejphar.2025.177323</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Retinal pharmacodynamic and pharmacokinetic profile of cannabidiol in an in vivo model of retinal excitotoxicity

Popis výsledku v původním jazyce

Cannabidiol (CBD) is one of the principal constituents of Cannabis Sativa with no psychoactive properties. CBD is a promising neuroprotective compound bearing anti-inflammatory and antioxidant properties. However, considering its low solubility, CBD delivery to the retina represents an unresolved issue. The first aim was to investigate the potential neuroprotective effects of CBD in an in vivo model of retinal excitotoxicity induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Rats underwent intravitreal co-injection of AMPA (42 nmol) and CBD (10- 4 M). The neuroprotective effect of CBD was investigated with histology and immunohistochemical evaluation of inflammatory and oxidative stress biomarkers. CBD reversed the AMPAinduced total retinal, inner nuclear layer and inner plexiform layer shrinkage and loss of amacrine cells. Moreover, CBD decreased the AMPA induced number of cleaved caspase-3, Iba-1 and nitrotyrosine (NT) positive cells. Based on this evidence, we developed a nanotechnological formulation of CBD to overcome critical issues related to its eye delivery. Particularly, nanostructured lipid carriers (NLC) loaded with CBD were prepared, optimized and characterized. Due to the optimal physicochemical characteristics, CBD-NLC3 has been selected and the in vitro release profile has been investigated. Additionally, CBD-NLC3 was topically administered to rats, and retinal CBD levels were determined. CBD-NLC3 formulation, after a single topical administration, efficiently delivered CBD in the retina (Cmax = 98 +/- 25.9 ng/mg; Tmax = 60 min), showing a high translational value. In conclusion, these findings showed a good PD/PK profile of CBD warranting further pre-clinical and clinical evaluation of the new formulation for the treatment of retinal degenerative diseases.

Název v anglickém jazyce

Retinal pharmacodynamic and pharmacokinetic profile of cannabidiol in an in vivo model of retinal excitotoxicity

Popis výsledku anglicky

Cannabidiol (CBD) is one of the principal constituents of Cannabis Sativa with no psychoactive properties. CBD is a promising neuroprotective compound bearing anti-inflammatory and antioxidant properties. However, considering its low solubility, CBD delivery to the retina represents an unresolved issue. The first aim was to investigate the potential neuroprotective effects of CBD in an in vivo model of retinal excitotoxicity induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Rats underwent intravitreal co-injection of AMPA (42 nmol) and CBD (10- 4 M). The neuroprotective effect of CBD was investigated with histology and immunohistochemical evaluation of inflammatory and oxidative stress biomarkers. CBD reversed the AMPAinduced total retinal, inner nuclear layer and inner plexiform layer shrinkage and loss of amacrine cells. Moreover, CBD decreased the AMPA induced number of cleaved caspase-3, Iba-1 and nitrotyrosine (NT) positive cells. Based on this evidence, we developed a nanotechnological formulation of CBD to overcome critical issues related to its eye delivery. Particularly, nanostructured lipid carriers (NLC) loaded with CBD were prepared, optimized and characterized. Due to the optimal physicochemical characteristics, CBD-NLC3 has been selected and the in vitro release profile has been investigated. Additionally, CBD-NLC3 was topically administered to rats, and retinal CBD levels were determined. CBD-NLC3 formulation, after a single topical administration, efficiently delivered CBD in the retina (Cmax = 98 +/- 25.9 ng/mg; Tmax = 60 min), showing a high translational value. In conclusion, these findings showed a good PD/PK profile of CBD warranting further pre-clinical and clinical evaluation of the new formulation for the treatment of retinal degenerative diseases.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Pharmacology

ISSN

0014-2999

e-ISSN

1879-0712

Svazek periodika

991

Číslo periodika v rámci svazku

177323

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

14

Strana od-do

1-14

Kód UT WoS článku

001422901700001

EID výsledku v databázi Scopus

2-s2.0-85216527547