Abstract
<title>Abstract</title> <p> <bold>Background:</bold> Parkinson's Disease is the second most common neurodegenerative disorder worldwide. Although levodopa and monoamine oxidase-B (MAO-B) inhibitors remain the cornerstone of symptomatic management, oral administration is often limited by poor brain targeting and restricted penetration across the blood–brain barrier. The present study aimed to develop and optimize a thermoresponsive nasal in situ gel of Rasagiline Mesylate to facilitate direct nose-to-brain delivery. <bold>Materials and Methods:</bold> A Central Composite Design (CCD) was employed to optimize the formulation. Poloxamer 407 (A: 15–30%, including axial points of 11.89 and 33.11%) and dodecyl maltoside (B: 1.0–2.0%, including axial points of 0.79 and 2.21%) were selected as independent variables, while gelation time, mucoadhesive strength, and permeation coefficient were considered response variables. The developed formulations were characterized for gelation time, mucoadhesive strength, drug content, pH, gelation temperature, viscosity, in vitro permeation, droplet size distribution, and plume geometry. <bold>Results:</bold> The optimized formulation (RM1; 22.5% Poloxamer 407 and 1.5% dodecyl maltoside) demonstrated rapid thermogelation at physiological temperature (36–37 s), favourable mucoadhesive strength (~2000 dyne/cm²), and an enhanced permeation coefficient (0.00203 cm/s). In contrast, formulations containing higher polymer concentrations (RM10; 30% Poloxamer 407 and 2% dodecyl maltoside) exhibited prolonged gelation and reduced permeation performance. All formulations maintained a pH of approximately 7.3, indicating suitability for nasal administration. The optimized gel also exhibited acceptable spray characteristics, viscosity, and drug content uniformity. <bold>Conclusion:</bold> The optimized thermosensitive nasal in situ gel of rasagiline mesylate demonstrated desirable physicochemical properties, mucoadhesion, and permeation behavior, supporting its potential as a non-invasive nose-to-brain delivery platform. This approach may enhance central nervous system targeting of MAO-B inhibitors and represents a promising strategy for improving therapeutic outcomes in Parkinson’s disease. </p>