Comparative Evaluation of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Drug Delivery of Prilocaine Hydrochloride

Lipid-based nanocarriers have gained significant attention for enhancing drug solubility, bioavailability, and controlled release. This study presents a systematic comparative evaluation of Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) formulated with prilocaine hydrochloride as a model local anesthetic. Both systems were prepared using hot high-pressure homogenization and characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, morphology, in vitro drug release, and stability. SLNs exhibited smaller particle size (168.4 ± 5.2 nm) and higher zeta potential (–31.2 ± 1.4 mV), whereas NLCs showed significantly higher entrapment efficiency (92.4 ± 1.9% vs. 84.6 ± 2.1%) and superior long-term stability. In vitro release studies over 48 h revealed a burst release (~32% in 4 h) followed by sustained release in SLNs, and a more controlled release profile (~24% in 4 h) in NLCs. Kinetic modeling indicated Higuchi diffusion for SLNs and Korsmeyer–Peppas Fickian diffusion for NLCs. Stability testing over 3 months confirmed minimal changes at 4 °C, with NLCs demonstrating better retention of physicochemical properties at 25 °C. These findings suggest that while SLNs are preferable for rapid-onset delivery, NLCs offer advantages in sustained drug release, higher payload capacity, and improved stability, making them promising candidates for long-acting topical and transdermal anesthetic applications.