Nanogel system loaded with nanosuspension is a promising approach for nose to brain delivery in order to reduce dose and dosing frequency an also helps to improve the bioavailability of the drug. The present study attempt was made to develop the Nanosuspension loaded Insitu nasal nanogel of the Nortryptiline HCl (NTH) to get an effective administration through intranasal route to reaches to the brain via olfactory and trigeminal nerves to improve the therapeutic efficiency. Nanoprecipitation-Ultrasonication method followed by high pressure homogenization was elected for preparation of nanosuspension which further incorporated into insitu gelling polymer solution. Optimized nanosuspension loaded nanogel was prepared by using gellan gum. Optimized formulation shows average particle size of 10-100 nm and good PDI value, increase in solubility and also shows high
entrapment efficiency 92.30 ± 2.23%. The formulation containing 0.5% gellan gum shows good gelation property and desired viscosity to adhere at
the nasal mucosa after ionic interactions. Invitro drug release was found to be more than drug solution over period of 60 min. Spreadability, and viscosity studies shows better results for getting good residence time. Hence, it was proved that insitu nanogel is one of the best possible approach for the targeting of drug towards brain in nanoform.