There is a crucial need for long-acting local anesthetics (LAs) that can be administered as single dose analgesics. However, owing to their low molecular mass, LAs (lidocaine, bupivacaine, procaine, ropivacaine, and benzocaine) display rapid and complete absorption. The goal of the current study (LDC@LPHNs) was to progress and assess lidocaine (LDC) hybrid lipid-polymer nanoparticles (LPHNs) in comparison to LDC-loaded PLGA NPs (LDC@NPs). The morphology, zeta potential, particle size, and drug loading abilities of the newly fabricated materials were examined. The self-assembled LDC@LPHNs combined with PLGA, DSPE-PEG(2000), and lecithin were approximately 180 nm in size, were larger than LDC@LPHNs and LDC@NPs and showed a protracted in vitro drug release profile in PBS solution. Additionally, the LDC@LPHNs exhibited improved stability and less in vitro cytotoxicity. Furthermore, in vivo examination of the anesthetic properties in mice models showed that the LDC@LPHNs displayed remarkable protracted analgesic durations, which was further confirmed through histological examinations. These outcomes establish that the LDC@LPHNs could purpose as a potential framework of drug conveyance to address the disadvantages of less stability, quick release of drug, and to extend anesthetic effects with less toxicity.