Lopinavir is a specific reversible inhibitor of the enzyme HIV protease with mean oral bioavailability of less than 20 % due to extensive hepatic metabolism by cytochrome P450 3A4. The reported half-life of Lopinavir is 5-6 hours and the maximum recommended daily dose is 400 mg/day. All the marketed tablet and capsule formulations of lopinavir are generally combined with Ritonavir, a potent inhibitor of cytochrome P450 3A4, to minimize presystemic metabolism of lopinavir. Hence, to overcome limitations associated with oral administration of lopinavir and to promote single drug administration, utilization of vesicular nanocarriers through topical route could prove to be effective, as the approach combines the inherent advantages of topical route and the drug-carrying potential of vesicular nanocarriers across the tough and otherwise impervious skin barrier layer, i.e., stratum corneum. The objective was to develop solid lipid nanoparticles (SLN) of lopinavir and formulate a topical gel for improved systemic bioavailability of lopinavir. SLNs were prepared using high-pressure homogenization technique and optimized. The nanoparticles were characterized by SEM to confirm their spherical shape. Differential Scanning Calorimetry (DSC) analysis was carried out to ensure the entrapment of drug inside the SLNs. A comparative evaluation was done between SLN based gel and plain gel of drug by performing exvivo skin permeation studies using Franz diffusion cell. To explore the potential of topical route, invivo bioavailability study was conducted in male Wistar rats. The optimized formulation composed of Compritol 888ATO (0.5 %) as a lipid, Poloxamer 407 (0.25 %) as a surfactant and Labrasol (0.25 %) as a co-surfactant gave the maximum entrapment of 69.78 % with mean particle size of 48.86nm. The plain gel of the drug gave a release of 98.406 ± 0.007 % at the end of 4hours whereas SLN based gel gave a more sustained release of 71.197 ±0.006 % at the end of 12hours ex-vivo. As observed from the results of in-vivo studies, highest Cmax was found with SLN based gel (20.3127 ± 0.6056) µg/ml as compared to plain gel (8.0655 ± 1.6369) µg/ml and oral suspension (4.2550 ± 16.380) µg/ml of the drug. Also, the AUC was higher in the case of SLN based gel indicating good bioavailability as compared to oral suspension and plain gel of drug. Lopinavir SLN based gel was found to have modified drug release pattern providing sustained release as compared to plain drug gel. This indicates that Lopinavir when given topically has a good potential to target the HIV as compared to when given orally.