Prilocaine Hydrochloride

Prilocaine hydrochloride produces vasodilatation in human skin following intradermal injection. To investigate the mechanisms underlying this vasoactive effect, prilocaine 1% was injected into the forearm skin of ten healthy male subjects, either alone or co-injected with the nitric oxide synthase inhibitor L-NAME. Skin blood flow was measured using laser Doppler imaging. After the traumatic effects of injection had subsided, co-injection with L-NAME reduced the vascular response to prilocaine by one third, indicating that the vasodilator effect is mediated in part through the release of endothelial nitric oxide. In contrast, pre-treatment with aspirin to block the cyclo-oxygenase pathway had no significant effect on the prilocaine-induced blood flow response, demonstrating that prostaglandins do not contribute to this vasoactivity. This study established that prilocaine stimulates the endothelium to produce nitric oxide via an as-yet unidentified mechanism, leading to local vasodilatation.

Fig. 1 Skin blood flow responses to the intradermal injection. (Newton D J.; et al. 2003)

Prilocaine hydrochloride was encapsulated together with lidocaine in lipid nanocapsules prepared by the phase inversion temperature method, followed by incorporation into a Carbopol gel for topical application. The lipid nanocapsules exhibited a homogeneous size of 50 nm with a polydispersity index of 0.05, negative zeta potential of -21 mV, and high encapsulation efficiency of 81 percent for prilocaine and 89 percent for lidocaine. The hybrid system consisting of drug-loaded nanocapsules in gel produced a four-fold increase in anesthesia duration compared to an equipotent conventional gel formulation in a mouse tail flick test. Histological examination confirmed no tissue damage.

Fig. 2 Comparison of anesthesia duration in mice anesthesia experiments. (Fernandes P C L.; et al. 2021)