Design of patient acceptable and effective drug delivery systems is a major concern area in pharmaceutical research field especially when the aim is management of nasal and respiratory infections. This paper was an attempt to design and optimize a thermoresponsive in-situ nasal gel made with nanosized antiviral agent using Poloxamer 407, Poloxamer 188, and HPMC as variables of the formulation. To determine the impact of these variables on the gelation temperature, viscosity and drug release, a Box- Behnken design was used together with Response Surface Methodology (RSM). ANOVA showed the effect of three excipients to be significant (p