Development and Characterization of Novel Combinations and Compositions of Nanostructured Lipid Carrier Formulations Loaded with Trans-Resveratrol for Pulmonary Drug Delivery

Background/Objectives: This study aimed to fabricate, optimize, and characterize nanostructured lipid carriers (NLCs) loaded with trans-resveratrol (TRES) as an anti-cancer drug for pulmonary drug delivery using medical nebulizers. Methods: Novel TRES-NLC formulations (F1–F24) were prepared via hot, high-pressure homogenization. One solid lipid (Dynasan 116) was combined with four liquid lipids (Capryol 90, Lauroglycol 90, Miglyol 810, and Tributyrin) in three different ratios (10:90, 50:50, and 90:10 w/w), with a surfactant (Tween 80) in two different concentrations (0.5 and 1.5%), and a co-surfactant, soya phosphatidylcholine (SPC S-75; 50 mg). Results: Amongst the analyzed 24 TR-NLC formulations, F8, F14, and F22 were selected based on their physicochemical stability when freshly prepared and following storage (4 weeks 25 °C), as well as in terms of particle size (96%). Furthermore, F14 showed greater stability at 4 and 25 °C for six months and exhibited enhanced aerosolization performance, demonstrating the greater deposition of TRES in the later stages of the next-generation impactor (NGI) when using an air-jet nebulizer than when using an ultrasonic nebulizer. The F14 formulation exhibited greater stability and release in acetate buffer (pH 5.4), with a cumulative release of 95%. Conclusions: Overall, formulation F14 in combination with an air-jet nebulizer was identified as a superior combination, demonstrating higher emitted dose (ED; 80%), fine particle dose (FPD; 1150 µg), fine particle fraction (FPF; 24%), and respirable fraction (RF; 94%). These findings are promising in the optimization and development of NLC formulations, highlighting their versatility and targeting the pulmonary system via nebulization.