Abstract : The detection and treatment of numerous diseases, including HIV/AIDS, can be completely transformed by engineered nanoparticles. One of the main components of antiretroviral therapy for HIV-1 infections is etravirine. The current study’s objective was to create and assess solvent emulsification-evaporation-based nanostructured lipid carriers containing etravirine that were meant to be specifically delivered to macrophages. The selection of liquid and solid lipids as well as stabilisers for the creation of NLCs was done using estimates of drug solubility. Utilising a 3² full factorial design, the formulation was optimized with regard to the drug-lipid ratio and stabilizer concentration in the external phase. The responses that were predetermined were the drug release properties and the particle size of the carriers. The optimized formulation was prepared and subjected to characterization which includes size, entrapment efficiency, zeta potential, polydispersity index and appearance. Stearylamine and glyceryl monostearate were used as solid lipids, Capryol 90 was used as liquid lipid and polyvinyl pyrrolidone was used as a stabilizer to create nanostructured lipid carriers of etravirine. High drug loading efficiencies approaching 99% were demonstrated by all testing batches, suggesting that etravirine remained closely associated with the lipids. The nanostructured lipid carriers had a polydispersity index of 0.374, a particle size of 261.6 nm and a zeta potential of -10.1 mv. The in vitro release of etravirine from the optimized formulation at 2 h was 9% indicating a mild burst and 56% of the drug that had been entrapped was released after 24h indicating extended-release characteristics. Consequently, etravirine-loaded lipidic nanoparticles that have the ability to target AIDS virus-carrying cells like macrophages were effectively developed.