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SLNs and NLCs were prepared by high shear homogenization followed by ultrasonication method, using different types of solid lipids such as glyceryl monostearate, stearic acid and Compritol 888 ATO. Isopropyl myristate, as a liquid lipid in formulation of NLCs was used in different ratios to study the influence of liquid lipid content on the particle size, entrapment efficiency and zeta potential of the formulated benzocaine loaded lipid nanoparticles. The results indicated that entrapment efficiency and particle size depend on the concentration and the lipid mixture employed. The selected NLCs (NLC6) was further incorporated in 5% carboxymethyl cellulose (CMC) hydrogel and then characterized for appearance, pH and in-vitro drug release. The prepared SLNs and NLCs possessed an average particle size of 214 – 440 nm, zeta potential of (-19.6) to (-25.9) mV and 55.65 – 94.62 % entrapment efficiency. The prepared NCL6 loaded hydrogel showed a smooth texture hydrogel free from any agglomeration of lipid nanoparticles with pH value of 6.10.The release studies of the investigated NLC6 showed an initial fast release that lasted for 0–1 hr, followed by a sustained release for 8 hrs.These promising findings encourage the potential use of benzocaine loaded lipid nanoparticles for future topical application improving its therapeutic efficacy for topical treatment of pain.en-USHydrogelTopical deliverySolid lipid nanoparticlesNanostructured lipid carriersBenzocaineLipid-Based Drug Delivery Systems for the Enhancement of Topical Delivery of Benzocaine.Articlehttps://doi.org/