Cannabidiol-Loaded Mesoporous Silica SBA-15: Physicochemical Characterization and Biological Evaluation in 2D and 3D Non-Small Cell Lung Cancer Models

Background/Objectives: Cannabidiol (CBD) exhibits cytotoxic activity against cancer cells, but its poor aqueous solubility may limit its pharmaceutical application. This study investigated Santa Barbara Amorphous No. 15 (SBA-15) mesoporous silica as a CBD carrier and evaluated its biological effects in A549 and HCC827 non-small cell lung cancer cell lines using 2D and 3D culture models. Methods: SBA-15 was loaded with 40 or 50 wt% CBD by melt infiltration and characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and transmission electron microscopy (TEM). Free and SBA-15-loaded CBD were evaluated using the PrestoBlue assay in 2D cultures, live/dead fluorescence imaging in 3D spheroids, and YO-PRO-1/PI flow cytometry. Preliminary short-term survival was assessed in Galleria mellonella larvae at a single dose, with five larvae per group. Results: The mesoporous structure of SBA-15 was preserved after CBD loading. At 40 wt%, CBD was predominantly amorphous and confined within the pores, whereas at 50 wt%, partial crystallization outside the silica matrix was observed. The PrestoBlue results indicated that A549 cells were more sensitive than HCC827 cells to the CBD-containing formulations. SBA-15 alone did not reduce cell viability. Both cell lines were less sensitive under 3D conditions. Flow cytometry demonstrated increased membrane permeabilization, with limited YO-PRO-1-positive/PI-negative populations. No reduction in larval survival was observed under the tested conditions. Conclusions: CBD loading affected its physical state within SBA-15 but did not substantially alter its cytotoxic activity in 2D cultures. Whether SBA-15 improves CBD dissolution remains to be determined. Biological responses depended on the cell line and culture dimensionality. Unloaded SBA-15 did not markedly reduce cellular metabolic activity, and no larval mortality was observed at the single tested dose. Cancer selectivity could not be assessed because non-malignant lung cells were not included.