The objective of this study was to formulate dolutegravir sodium an antiretroviral drug into topical (vaginal) semisolid solid lipid nanoparticle gel formulation using a rapid, economical one step process. Solid lipid nanoparticles formulations were prepared using solvent injection method combined with sonication, using different type of lipids (e.g. Phospholipon 80H, Phospholipon 90H and Soy lecithin) and surfactants (Poloxamer 407, Poloxamer 188, and Tween 80). The SLN gel was formed in one step process using poloxamer 407 & water forming aqueous phase and stearic acid & phospholipon 80H in ethanol forming lipid phase. The lipid phase was injected into aqueous phase forming a creamy gel at 70⁰ C. Hence it does not require any gelling agent. It was optimized using a systematic approach of design of experiments. The formulation was evaluated for particle size, polydispersity index, zeta potential, flux, entrapment efficiency and results were found to be 455 nm, 0.411, -26.6 mV, 43.7±-0.12 µg/cm2/hr, 76.2% respectively. Drug release studies were conducted using two membranes via; dialysis membrane and goat vaginal tissue. The release pattern of the drug followed first order kinetics with Higuchi release mechanism. The release exponent ‘n’ of the Korsemeyer equation indicates the Fickian diffusional drug release. The ex vivo vaginal study of F2 formulation showed 64.89% of tissue deposition, which was 16 times more than the pure drug. This study concluded that the dolutegravir sodium, a sustained release solid lipid nanoparticle gel may have increased vaginal deposition and might show site targeted effect.