Benzocaine

Benzocaine acts through reversible binding to and inhibition of sodium channels in the neuronal cell membrane. Benzocaine, in its nonionized form, penetrates the cell, where it then becomes ionized after crossing the membrane bilayer. In its ionized form, benzocaine then binds to the α subunit, blocking voltage-gated sodium channels. The result of this inhibition of sodium channels is an inability to depolarize the cell, which slows signal conduction and decreases the ability for an action potential to occur. Local anesthetics, such as benzocaine, bind more easily to sodium channels in their open conformation.

Nanostructured lipid carriers (NLC) are a relatively new class of drug delivery systems with some advantages over other lipid-based carriers, such as liposomes or solid lipid nanoparticles. Benzocaine (BZC) is the oldest topical local anesthetic still in use, and one of its metabolites, produced by pseudocholinesterase metabolism, is p-aminobenzoic acid, which is the causative factor for the allergic reactions related to prolonged BZC use. To reduce side effects and improve bioavailability, BZC was incorporated into NLC. A 2³ factorial design was applied to prepare formulations composed of cetyl palmitate (solid lipid), propylene glycol monocaprylate (liquid lipid) and Pluronic F68 as surfactants, varying the solid/liquid lipid mass ratio, total lipid contents and BZC concentrations. The optimized formulation was characterized by dynamic light scattering, differential scanning calorimetry, Raman imaging, X-ray diffraction, small-angle neutron scattering, nanotracking analysis and transmission electron microscopy (TEM)/cryo-TEM, which contributed to the understanding of the structure of the nanoparticles and how BZC is accommodated in its lipid matrix. NLC_BZC had a high encapsulation efficiency (%EE = 96%) and a 1 year shelf life at 25 °C. In vitro kinetic studies and in vivo antinociceptive studies in mice demonstrated that NLC_BZC was able to prolong drug release for over 20 h and the anesthetic effect of BZC for up to 18 h.

Fig. 2 A fresh carrier for an old topical local anesthetic: Benzocaine in nanostructured lipid carriers. (Souza A D, et al. 2024)