Abstract
Lipid nanocapsules (LNC) are special drug delivery system (DDS) carriers obtained by the phase-inversion temperature method (PIT). This study describes the encapsulation of the local anesthetics (LA) prilocaine (PLC) and lidocaine (LDC) in lipid nanocapsules (LNCPLC+LDC) optimized by 23 factorial design, characterized through DLS, NTA, CRYO-EM and release kinetics and incorporated in carbopol gel (GelLNC PLC+LDC) prior to in vivo anesthetic effect (in mice) evaluation. A very homogeneous population of small (50 nm; polydispersity index = 0.05) spherical nanocapsules with negative zeta potentials (−21 mV) and ca. 2.3 × 1015 particles/mL was obtained. The encapsulation efficiency was high (81% and 89% for prilocaine and lidocaine, respectively). The release rate profile was free PLC = free LDC > LNCPLC+LDC > GelLNC PLC+LDC. The hybrid system increased (4x) the anesthesia time in comparison to an equipotent gel formulation prepared without LNC. No tissue damage was detected on the tail skin of mice that received the formulations. This study shows that lipid nanocapsules are suitable carriers for PLC and LDC, promoting longer and safer topical anesthesia. GelLNC PLC+LDC is mucoadhesive and suitable for application in the mouth, where it could be used as a pre-anesthetic, to reduce pain of needle stick (infiltrative anesthesia).
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