Nanostructured lipid carrier to overcome stratum corneum barrier for the delivery of agomelatine in rat brain; formula optimization, characterization and brain distribution study

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.

Automated summary

This work successfully achieved bypassing hepatic metabolism, controlled release, and enhanced brain distribution of agomelatine by loading it into nanostructured lipid carriers (NLC) and administering via transdermal route. The optimized AG-NLC showed improved solubility and skin permeation, suggesting the NLC-gel system may offer a promising strategy for enhancing brain delivery of agomelatine.