Nature-based nanostructured lipid carriers containing β-caryophyllene for skin cancer adjuvant therapy: Development and study of their bioactivities in vitro

Modern medicine has made significant progress by incorporating natural bioactive compounds, not only as active ingredients but also as functional excipients. This study aimed to develop naturally derived nanostructured lipid carriers (NLCs) containing β-caryophyllene as a therapeutic adjuvant for the treatment of skin cancer. To identify the optimal combination among passion fruit oil, beeswax, soy lecithin, and β-caryophyllene, a component screening was performed. The formulations’ stability was monitored by particle size analysis and macroscopic evaluation over 30 days. Transmission electron microscopy of the optimized systems revealed the typical spherical morphology of NLCs. They exhibited drug entrapment efficiency higher than 92%. The lipid matrix, surrounded by the surfactant layer, effectively protected β-caryophyllene from volatilization. The release profile appeared to follow anomalous transport behavior. Photoacoustic spectroscopy indicated that β-caryophyllene could permeate into the dermis. Two selected systems (F3 and F21) enhanced the cytotoxic selectivity of β-caryophyllene against representative melanoma cells (B16-F10), with selectivity indices of 2.07 and 2.2, respectively. Overall, the developed systems demonstrated physicochemical and therapeutic characteristics that support their potential as adjuvants for the topical treatment of skin cancer. Future in vivo studies are warranted to confirm this potential. • The influence of natural lipids and surfactants on size and PDI of NLCs was studied. • Passion fruit oil, beeswax and lecithin amounts influenced the physicochemical stability of NCLs. • Selected formulations displayed in vitro antitumor activity against B16-F10 cells. • NLCs composed of passion fruit oil, beeswax and lecithin resulted in structured systems with improved properties for skin administration of BCP. • NLCs showed efficacy against B16-F10 tumor cells and low toxicity to VERO/L-929 cells.