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In this education article, we trace the development of LB, summarize the important aspects of its pharmacology, and explore possible causes of its failure to fulfill the promise that the drug held when it was developed and approved. Finally, we discuss some aspects of perineural anatomy that might impact the potential of this drug to provide long-lasting analgesia.<\/jats:p>","DOI":"10.1136\/rapm-2024-106189","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T18:05:23Z","timestamp":1739815523000},"page":"349-356","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Liposomal bupivacaine: examining the factors behind inconsistent analgesic results"],"prefix":"10.1136","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9517-6575","authenticated-orcid":false,"given":"Steven L","family":"Orebaugh","sequence":"first","affiliation":[{"name":"Anesthesiology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Ligocki","sequence":"additional","affiliation":[{"name":"Anesthesiology, Hospital for Special Surgery, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Guo","sequence":"additional","affiliation":[{"name":"Anesthesiology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Anesthesiology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"key":"2026031205150959000_51.3.349.1","doi-asserted-by":"publisher","DOI":"10.1213\/00000539-198867110-00010"},{"key":"2026031205150959000_51.3.349.2","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200510000-00026"},{"key":"2026031205150959000_51.3.349.3","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1213\/00000539-199403000-00026","article-title":"Eutectic mixture of local anesthetics (EMLA) cream","volume":"78","author":"Gajraj","year":"1994","journal-title":"Anesth Analg"},{"key":"2026031205150959000_51.3.349.4","doi-asserted-by":"publisher","DOI":"10.2174\/138945011795906570"},{"key":"2026031205150959000_51.3.349.5","first-page":"1","article-title":"Lipid-Based Drug Delivery Systems","volume":"2014","author":"Shrestha","year":"2014","journal-title":"J Pharm (Cairo)"},{"key":"2026031205150959000_51.3.349.6","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200645120-00002"},{"key":"2026031205150959000_51.3.349.7","doi-asserted-by":"publisher","DOI":"10.2174\/156720107782151269"},{"key":"2026031205150959000_51.3.349.8","first-page":"10","article-title":"Liposomes: A novel drug delivery system","volume":"3","author":"Kulkarni","year":"2011","journal-title":"Int J Curr Pharmaceutical Res"},{"key":"2026031205150959000_51.3.349.9","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/0005-2736(83)90504-7","article-title":"Preparation of multivesicular liposomes","volume":"728","author":"Kim","year":"1983","journal-title":"Biochim Biophys Acta"},{"key":"2026031205150959000_51.3.349.10","unstructured":"Mantripragada S . 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