Poloxamer-407 thickened lipid colloidal system of agomelatine for brain targeting: Characterization, brain pharmacokinetic study and behavioral study on Wistar rats

Publication date: Available online 8 May 2019Source: Colloids and Surfaces B: BiointerfacesAuthor(s): Shakeeb Ahmed, Azka Gull, Mohd. Aqil, Mohd Danish Ansari, Yasmin SultanaAbstractThe current study was designed to enhance the brain bioavailability and to extract maximum therapeutic benefit from a novel antidepressant drug, agomelatine. For this purpose, a thermoresponsive in situ gel was prepared by dissolving 20% w/v of Poloxamer-407 in agomelatine containing nanoemulsion. To impart mucoadhesive property, 0.5% w/v concentration of chitosan was ensured in the final formulation, named as Ago-NE-gel+0.5%chitosan. The gelling point and mucoadhesive strength of Ago-NE-gel+0.5%chitosan were found to be 28 ± 1 °C, and 6246.27 dynes/cm2 respectively. The size of free micelles of Poloxamer-407 was recorded graphically at 18.43 ± 0.95 nm whereas the size of sterically stabilized Ago-NE was observed at 142.58 ± 4.21 nm. The viscosity and pH of Ago-NE-gel+0.5%chitosan were found to be 2439 ± 23 cP (at 35 ± 1 °C temperature) and 5.8 ± 0.2 respectively. The developed formulation was found safe on nasal mucosa during the toxicity study. CLSM based brain distribution study suggested that Ago-NE-gel+0.5%chitosan is more competent to deliver the drug into the brain as compared to agomelatine-suspension. After intranasal administration of Ago-NE-gel+0.5%chitosan in Wistar rats, the AUC0-8h in brain and plasma were found to be 1418.591 ± 71.87 ...
Source: Colloids and Surfaces B: Biointerfaces - Category: Biochemistry Source Type: research