Solid lipid nanoparticles of a poorly soluble drug Delavirdine were successfully developed and optimized using the systematic approach of design of experiments (DoE) by high pressure homogenization technique. Thermosensitive in-situ gel was prepared with the optimized SLN dispersion. The intranasal administration of the formulation showed better absorption potential of the drug from Delavirdine loaded SLN formulation in comparison to the SLN Dispersion Studies. Thus, it may be concluded that the developed formulation has better potential to target brain where the HIV viruses are reported to harbor even with low dose of Delavirdine, rendering the treatment more cost-effective as well and acceptable to patients because of convenience of application of in-situ gelling formulation. Hence, the developed formulation, after necessary investigations of clinical trials, has the promising potential for an attempt to completely eradicate HIV reservoir and cure AIDS.