Enantiomeric Excess Bupivacaine in a Lavender Oil NLC Tested in a Melanoma Model: Prolonged Release and Anticancer Effect

Recent studies have highlighted the potential of local anesthetics (LA) as adjuvants in cancer treatment, specifically by increasing survival rates when used in surgical excisions. However, the clinical use of LA is restricted due to their systemic toxicity. The development of drug delivery systems could address this issue and advance the utilization of these molecules. In this research, we explored the pharmacokinetics (using microdialysis probes) and antitumor properties of a nanostructured lipid carrier (NLC) formulation containing the commercially available enantiomeric excess form of bupivacaine (BVC_S75). This NLC was prepared with lavender oil (NLC-L-BVC), an excipient with inherent antitumor properties. We compared this formulation to a control (NLC-BVC) using synthetic lipids. Pharmacokinetic assessments of the NLCs confirmed the sustained release of BVC_S75 within the tumor, characterized by a reduced elimination rate constant and longer half-life (∼6×). The encapsulation of BVC_S75 within nanoparticles (whether natural or synthetic) enhanced its effectiveness in treating the primary tumor, resulting in the inhibition of tumor growth (70% with NLC-L-BVC and 72% with NLC-BVC), outperforming free BVC (17% inhibition). However, the association of lavender oil with BVC_S75 in an NLC did not yield synergistic properties. Furthermore, all BVC_S75 treatments (whether free or encapsulated) improved animal survival rates. These findings confirm that encapsulation of bupivacaine in NLC can prolong drug action at the local site, contributing to improved local antitumor therapy while mitigating systemic effects.