Formulation, Optimization and Characterization: Thermosensitive Intranasal Nanostructured Lipid Carrier (NLC) In-situ Gel of Novel Agomelatine to Overcome the Limitations of Oral Delivery
Abstract
Agomelatine (AG), the first-in-class melatonergic antidepressant used in Major Depressive Disorder (MDD), belongs to BCS Class-II with low oral bioavailability (<5%) due to extensive hepatic metabolism. This research work developed a thermosensitive in-situ gel using nanostructured lipid carriers (NLC) for intranasal delivery as alternate route, aiming to bypass hepatic metabolism, enable controlled release, and enhance cerebral distribution. FTIR ensured compatibility with lipids, surfactants and polymers. AG-NLCs were synthesized utilizing hot high-speed homogenization with 5 mg agomelatine dose and optimized with 32 factorial design with total lipids (Precirol® ATO 5:Oleic acid – 70:30) and surfactant concentration (% of Poloxamer 188) as independent two-factor variables. The optimized AG-NLC (AF8) showed particle size of 159.3 nm, zeta potential of -37.0 mV, and 58.14% entrapment efficiency. AF8 was further fabricated into in-situ gels using thermosensitive polymer Poloxamer 407 and sodium alginate as mucoadhesive polymer, with NLCG-4 (with 8% Poloxamer 407) as the optimized in-situ gel formulation. NLCG-4 had 95.16±0.90% drug content, excellent viscosity (1690.65 ±0.40 cP at 37℃), and gelled at 33.24±0.11℃ in 10.3±0.38 seconds, ideal for nasal mucosa. NLCG-4 exhibited a complete, prolonged release of 100.01±0.2% over 6 h, and SEM images confirmed spherical particles without aggregation. The above findings suggest that thermosensitive NLC in-situ gel could be a potential novel approach for enhanced direct nose-to-brain delivery of agomelatine, bypassing first-pass metabolism to treat depression. Further in vivo investigations are ongoing to establish and justify clinical applicability of the novel system.
Keywords: thermosensitive, in-situ gel, NLC, agomelatine, major depressive disorder, intranasal delivery, Design Expert, poloxamer 407.
Keywords:
thermosensitive, in-situ gel, NLC, agomelatine, major depressive disorder, intranasal delivery, Design Expert, poloxamer 407DOI
https://doi.org/10.22270/jddt.v14i12.6889References
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