Formulações de carreadores lipídicos nanoestruturados baseados em lipídios naturais com atividade anestésica

Abstract

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. It is considered a clinical condition when persisting for months or even years, as in chronic pain. Due to its long-term nature, chronic pain significantly compromises quality of life and mental health. The interaction of physical and emotional factors emphasizes the complexity of chronic pain and its management, requiring a multifactorial therapeutic approach. Local anesthetics (LAs) are widely used in the management of chronic pain. However, they present limitations such as short duration of action, systemic toxicity, and risk of dependence. Essential oils (EOs) have emerged as a promising alternative due to their biocompatibility and therapeutic properties, including analgesic and anesthetic effects. However, their physicochemical instability, toxicity, and high hydrophocity require strategies to enable their therapeutic use. Nanoencapsulation using nanostructured lipids carriers (NLCs) aims to overcome these challenges, improving delivery to biological tissues. In this study, 8 NLC formulations based on natural lipids, including anesthetic EOs, were developed. Long-term (365 days at 25 °C) and thermal physicochemical stability was monitored. The formulations with juniper (F3), lemongrass (F5), bergamot (F6), and melissa (F8) EOs exhibited the best structural properties after 1 year of monitoring. These formulations were evaluated for nanotoxicity and efficacy using an alternative biological model, Drosophila melanogaster (DM). Concentrations of 2.5, 1.25, and 0.625 mg/mL were safe, showing no toxicity. By the nociception test in DM larvae, F5 and F8 (2.5 mg/mL) approximately doubled and tripled the anesthesic effect compared to the untreated group, respectively. These systems were characterized by FTIR-ATR, DSC, and FE-SEM techniques, demonstrating compatibility among the excipients, thermal stability, and spherical morphology. Therefore, formulations F5 and F8 represent viable candidates to be further evaluated for safety and efficacy in more complex biological models, aiming to establish an alternative therapeutic option to the drugs traditionally used for pain management.