Nanocarriers Derived from <i>Annona squamosa</i> Seed Oil Amplify the Anti-inflammatory Effect of Carvacrol in Human Neutrophils

This research aimed to prepare nanoemulsions based on <i>Annona squamosa</i> seed oil (ASSO) for encapsulation of carvacrol (CARV) and subsequent evaluation of its cytotoxicity and anti-inflammatory potential in human neutrophils. The chemical composition of ASSO is rich in long-chain fatty acids, especially oleic and linoleic acids. The treatment of human neutrophils with ASSO demonstrated its low cytotoxicity (1-50 μg mL^-1), as well as anti-inflammatory effect at 25 and 50 μg mL^-1, being able to attenuate the release of myeloperoxidase (MPO). The nanocarriers presented colloidal stability with particle sizes around 170 nm, ζ-potential greater than |30 mV| and moderate polydispersity. The encapsulation efficiency of the nanosystems was greater than 99%, evidencing the effectiveness of the applied methodology for CARV entrapment. The drug release tests demonstrated that the nanoemulsions were able to prolong the carvacrol release process, with an accumulated release of 26% (745 μg) in 72 h, with the Korsmeyer-Peppas model being the one that best adjusted to the observed kinetics. CARV, carvacrol-loaded nanoemulsion (CNE), and blank nanoemulsion (BNE) showed low cytotoxicity (5-100 μg mL^-1) against human neutrophils and were able to reduce neutrophil degranulation. Notably, the CNE potentiated the anti-inflammatory effect of the CARV, demonstrating biological efficacy at lower concentrations (5 μg mL^-1) compared to the free drug (50 μg mL^-1). Thus, nanoemulsions based on ASSO were effectively enhanced the biological effects of CARV, positioning themselves as promising nanosystems for the encapsulation and delivery of lipophilic compounds.