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

• Main Authors: Ahmed, Shakeeb, Mahmood, Syed, Ansari, Mohd Danish, Gull, Azka, Sharma, Nitin, Sultana, Yasmin
• Format: Article
• Published: Elsevier 2021
• Subjects: RM Therapeutics. Pharmacology; RS Pharmacy and materia medica
• Online Access: http://eprints.um.edu.my/28379/
• Institution: Universiti Malaya

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.