Local anaesthetic pain relief therapy: In vitro and in vivo evaluation of a nanotechnological formulation co-loaded with ropivacaine and dexamethasone

Combination therapy is frequently applied to anesthesia and analgesia for its benefits, which includes prolonged analgesia following peripheral nerve blockade, and reduced side effects. The aim of this study was to develop chitosan (CH) coated poly(ε-caprolactone) (PCL) nanoparticles to co-deliver ropivacaine (RPV) and dexamethasone (DEM) (RPV/DEM CH-PCL NPs) for the prolongation of anesthesia and pain relief. In the present study, RPV/DEM CH-PCL NPs were fabricated. The properties of CH-PCL NPs were evaluated for their particle sizes, zeta potential, drug loading capacity and in vitro drug release profile. In vitro skin permeation and in vivo therapeutic effect in an animal model were further investigated. The results showed that the NPs was around 190nm, with PDI of less than 0.20. The zeta potentials of NPs were about 36mV. In vitro drug release of both RPV and DEM from NPs complied with sustained behaviors. All of the drugs loaded NPs samples studied exhibited no obvious L929 cells cytotoxicity. In vitro skin penetration profiles showed the amount of RPV permeated through the skin from NPs was significantly higher than free RPV. RPV and DEM co-loaded NPs induced remarkably better anesthetic effect than non DEM loaded RPV CH-PCL NPs. The results suggested that adding a small dosage of DEM could improve the anesthesia efficacy of RVP to a large content. The resulting formulation could be applied as a promising anesthesia system for local anesthetics therapy.