BACKGROUND: Local anesthetics have been widely used to control postoperative pain and chronic pain. However, their usage in controlling long-lasting pain has been limited due to a relatively short duration of action. Many attempts have been made to develop a controlled release drug delivery system to provide long-lasting anesthesia. The goal of this study was to evaluate the histocompatibility and effectiveness of a new injectable lipid gel type drug delivery system (PHW, egg phosphatidylcholine/hyaluronic acid/water) using bupivacaine. METHODS: Eighty-four male Sprague-Dawley rats were divided into 3 groups; 44 in the bupivacaine group, 20 in the PHW-bupivacaine (PHW-B) group, and 20 in the PHW group; and each drug mixture was injected in a 0.1 ml solution near the sciatic notch. Motor block was assessed by direct observation of motor skills to splay toes. Sensory block was assessed by measuring withdrawal response latencies to radiant heat using an analgesiameter. Gross and microscopic examinations on the sciatic nerve and surrounding muscle were performed for 3weeks after the injection. RESULTS: Nerve block was significantly prolonged in the PHW-B group (190.0 +/- 42.8 min) compared to the plain bupivacaine group (99.0 +/- 30.5 min). There was no sign of nerve block in the PHW group. We observed moderate perimuscular inflammation in the PHW and PHW-B groups for the first 3 days. After 3 days, we did not observe inflammation of muscles and there was no sign of perineural inflammation. CONCLUSIONS: In conclusion, the histocompatibility of a bupivacaine incorporated PHW drug delivery system was satisfactory and the controlled releasing property of this drug delivery system was evaluated as effective.