Development and Characterization of Oral Efavirenz-Loaded Nanostructured Lipid Carriers and Their Optimization with...

To enhance brain delivery of efavirenz (EFV), optimized nanostructured lipid carriers (NLCs) were developed using a melt-emulsification technique and probe sonication. Box-Behnken design was chosen to systematically analyze the effects of variables on formulation outcomes, enabling efficient optimization with fewer experimental trials. This selection helped to improve the formulation by allowing us to refine key characteristics such as particle size, entrapment efficiency, and polydispersity index (PDI). The optimized EFV-NLCs had a mean particle size of 91.41 ± 7.90 nm, a PDI of 0.28 ± 0.04, a zeta potential of -17 mV, an entrapment efficiency of 85 ± 7%, and a drug loading of 14 ± 1%. Transmission electron microscopy confirmed that the EFV-NLCs were spherical with uniform size distribution. In vitro release tests showed prolonged drug release, with release rates ranging from 63.09 ± 2.76% to 84.43 ± 4.24% at pH 1.2 and 87.66 ± 6.31% to 92.56 ± 1.48% at pH 6.8. This was significantly better than the EFV suspension, which showed moderate and unsustainable release rates over 8 h. Furthermore, dissolution studies in both fasted and fed state simulated-intestinal-fluids (FaSSIF and FeSSIF) over 6 h revealed that % cumulative drug release was significantly higher in FeSSIF (94.06 ± 1.62%) compared with FaSSIF (65.21 ± 3.95%), indicating enhanced absorption in the presence of food. In vitro gut permeation studies revealed that EFV-NLCs had a 2.05-fold higher drug permeability than the suspension. These findings suggest that EFV-NLCs are promising for targeted brain delivery, are safe for oral administration, and could be instrumental in managing neuro-acquired immunodeficiency syndrome.