Agomelatine-based in situ gels for brain targeting via the nasal route: statistical optimization, in vitro, and in vivo evaluation.

Abstract:

:Agomelatine (AGM) is an antidepressant drug with a low absolute bioavailability due to the hepatic first pass metabolism. AGM-loaded solid lipid nanoparticles were formulated in the form of an in situ gel to prolong the intranasal retention time and subsequently to increase the absorbed amount of AGM. The optimized in situ gel formula had a sol-gel transition temperature of 31 °C ± 1.40, mucociliary transport time of 27 min ±1.41%, released after 1 and 8 h of 46.3% ± 0.85 and 70.90% ± 1.48. The pharmacokinetic study of the optimized in situ gel revealed a significant increase in the peak plasma concentration, area under plasma concentration versus time curve and absolute bioavailability compared to that of the oral suspension of Valdoxan® with the values of 247 ± 64.40 ng/mL, 6677.41 ± 1996 ng.min/mL, and 37.89%, respectively. It also gave drug targeting efficiency index of 141.42 which revealed more successful brain targeting by the intranasal route compared to the intravenous route and it had direct transport percent index of 29.29 which indicated a significant contribution of the direct nose to brain pathway in the brain drug delivery.

journal_name

Drug Deliv

journal_title

Drug delivery

authors

Fatouh AM,Elshafeey AH,Abdelbary A

doi

10.1080/10717544.2017.1357148

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

1077-1085

issue

1

eissn

1071-7544

issn

1521-0464

journal_volume

24

pub_type

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