Nanostructured lipid carrier to overcome stratum corneum barrier for the delivery of agomelatine in rat brain; formula optimization, characterization and brain distribution study
Document Type
Article
Publication Date
9-25-2021
Abstract
The current work attempted to achieve bypassed hepatic metabolism, controlled release, and boosted brain distribution of agomelatine by loading in NLC and administering via transdermal route. Agomelatine-loaded NLC (AG-NLC) was fabricated employing melt-emulsification technique and optimized using central composite design. The optimized AG-NLC had 183.16 +/- 6.82 nm particle size, 0.241 +/- 0.0236 polydispersity index, and 83.29 +/- 2.76% entrapment efficiency. TEM and FESEM visually confirmed the size and surface morphology of AG-NLC, respectively. DSC thermogram confirmed the conversion of AG from crystalline to amorphous form, which indicates improved solubility of AG when loaded in NLC. For further stability and improved applicability, AG-NLC was converted into a hydrogel. The texture analysis of AG-NLC-Gel showed appropriate gelling property in terms of hardness (142.292 g), cohesiveness (0.955), and adhesiveness (216.55 g.sec). In comparison to AG-suspension-Gel (38.036 +/- 6.058%), AG-NLC-Gel (89.440 +/- 2.586%) exhibited significantly higher (P < 0.005) skin permeation profile during the 24 h study. In the CLSM study, Rhodamine-B loaded AG-NLC-Gel established skin penetration up to the depth of 45 mu m, whereas AG-Suspension-Gel was restricted only to a depth of 25 mu m. gamma-scintigraphy in wistar rats revealed similar to 55.38% brain distribution potential of Tc-99m-AG-NLC-Gel at 12 h, which was 6.31-fold higher than Tc-99m-AG-Suspension-Gel. Overall, the gamma scintigraphy assisted brain distribution study suggests that NLC-Gel system may improve the brain delivery of agomelatine, when applied transdermally.
Keywords
Central Composite Design, Field Emission Scanning Electron Microscopy, Differential Scanning Calorimetry, Texture Analyzer, Confocal Laser Scanning Microscopy, Gamma Scintigraphy
Divisions
phartech
Funders
UGC-MANF (F1-17.1/2016-17/MANF-2015-17-BIH-61518)
Publication Title
International Journal of Pharmaceutics
Volume
607
Publisher
Elsevier
Publisher Location
RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS