LIPID NANOCAPSULE-LOADED HYDROGEL FOR SUSTAINED BUCCAL ANESTHESIA: CO-ENCAPSULATION OF BENZOCAINE AND EUGENOL

Benzocaine (BZC) is a topical anesthetic widely applied in dental procedures due to its effectiveness in relieving mucosal pain. However, its use is limited by systemic toxicity, mainly associated with p-aminobenzoic acid (PABA) a metabolite that induces methemoglobinemia. Eugenol (EUG), a natural lipophilic compound with anesthetic and bioactive properties, is also frequently used in dentistry. To improve safety and extend local anesthesia, lipid nanocapsules (LNCs) co-encapsulating BZC and EUG were developed. LNCs consisting of an oily core stabilized by non-ionic surfactants were produced by the phase-inversion, after preliminary solubilization, FTIR and Raman spectroscopy experiments that indicated favorable interactions between LNCs’ excipients and the active compounds. An optimized formulation from Design of Experiments (LNC_{BZC EUG}) and containing 0.5% BZC and 1.0% EUG was characterized by dynamic light scattering, electrophoretic mobility, nanoparticle tracking analysis, and cryo-transmission electron microscopy. LNC_{BZC EUG} showed mean particle sizes of 91.30 ± 0.95 nm, polydispersity index of 0.053 ± 0.017, zeta potential of –12.4 ± 3.4 mV, particle concentration of 3.14 × 10¹⁴ particles/mL, high encapsulation efficiency (> 99.5 % for BZC and EUG) and spherical and homogeneous morphology. For topical application, LNCs were incorporated into a Poloxamer 407 hydrogel and rheological analyses revealed its pseudoplastic and viscoelastic behavior, with a high rigidity, desirable for mucosal adhesion. In vitro release studies indicated that LNC_{BZC_EUG} gel promoted sustained drug release (~60% for BZC and ~85% for EUG in 24 h), with a release mechanism governed by diffusion and gel erosion. These results support the potential of LNC_{BZC_EUG} as a safe and effective platform for prolonged topical buccal anesthesia.