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Liposomes are microscopic phospholipid vessels that have been utilized to extend the action of topical medications. Previous studies have demonstrated that liposomal vehicles can prolong the action of a variety of medications, including antifungals, anesthetics, interferon, and antineoplastic agents.The purpose of this study was to examine the degree and duration of anesthesia produced by lidocaine in a liposomal vehicle compared with lidocaine in a nonliposomal vehicle and compared with EMLA. The topical preparations in this study were allowed to contact the skin for a 30-minute period prior to evaluation of anesthetic effectiveness. Unoccluded and Tegaderm-occluded topical preparations were evaluated in two separate arms of the study.Thirteen healthy volunteers (three male, 10 female) were recruited for the nonocclusion arm of the study. Six healthy volunteers (two male, four female) were recruited for the occlusion arm of the study. Subjects with a history of allergy to lidocaine, a history of seizures, cardiac or respiratory difficulty, pregnant patients, and patients less than 18 years old were excluded. Written informed consent was obtained from all patients prior to testing. The volar forearms of the volunteers were swabbed with isopropyl alcohol and allowed to dry. A template was then utilized to mark 2 × 2-cm squares with a skin marker on both volar forearms. In total, nine squares corresponding to nine test areas were marked. The nine test preparations were applied to the test areas in a double-blinded fashion using a clean swab stick. The test preparations were then allowed to remain on the skin for 30 minutes in either occluded or nonoccluded form depending upon the arm of the study. Following the 30-minute application period, the test preparations were wiped off with clean gauze. Testing for anesthesia was performed by following a previously published method utilizing gentle pinpricks. A new pinprick apparatus was used for each patient. Pinprick testing was performed at 0, 15, 30, 60, and 90 minutes following the end of the 30-minute application period. Patients' responses to the pinprick were recorded in a binary fashion, as being either: 1) totally painless or 0) painfully sharp to any degree. Ten applications of the pinprick were applied randomly across each 2 × 2-cm test area. The number of painless applications of the pinprick out of a total of 10 applications of the pinprick was then recorded for each test area at every particular test time. In total, nine test preparations were evaluated. Analysis of the data was performed by a PhD statistical faculty consultant from the UCLA Mathematics Department.Liposomal lidocaine preparations evidenced longer durations of anesthesia than lidocaine preparations in nonliposomal vehicles. Five percent liposomal lidocaine preparations were statistically equivalent to EMLA in anesthetic effectiveness.Five percent liposomal lidocaine is an effective alternative topical agent for use in the attainment of temporary local anesthesia of the skin.