Design of an innovative nanovehicle to enhance brain permeability of a novel 5-HT6 receptor antagonist
No Thumbnail Available
Date
2024
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
An innovative nanovehicle based on lipid nanocapsules (LNC) was designed to facilitate the passage of a new 5HT6 receptor antagonist, namely PUC-10, through the blood-brain barrier. PUC-10 is a new synthetic N-arylsulfonylindole that has demonstrated potent 5-HT6 receptor antagonist activity, but it exhibits poor solubility in water, which indicates limited absorption. The lipid nanocapsules designed had a nanometric size (53 nm), a monomodal distribution (PI<0.2), a negative Z potential (-17 +/- 7 mV) and allowed efficient PUC-10 encapsulation (74 %). Furthermore, the LNC demonstrated to be stable for at least 4 weeks at 4( degrees)C (storage conditions), for at least 4 h in DMEM at pH 7.4, and for 18 h in water with 5 % DMSO, with both latter conditions maintained at 37 C-degrees. They also demonstrated that cell viability was not affected at the different concentrations studied. Finally, in vitro studies that simulate the blood brain barrier (PAMPA-BBB) demonstrated that the nanoencapsulation of PUC-10 promoted their penetration through the blood-brain barrier, with a calculated permeability of 1.3 x 10(- 8 )cm/s, compared to the null permeability exhibited by non-nanoencapsulated PUC-10.
Description
Keywords
Lipid nanocapsules, PAMPA-BBB, Brain permeability, Arylsulfonylindoles, 5-HT6 receptor