title: Biocompatibility of lipid-protein-sugar particles containing bupivacaine in the epineurium.
abstract: Novel lipid-protein-sugar particles (LPSPs) are potentially biocompatible because they are composed of naturally occurring ingredients and their expected tissue dwell times are relatively short. In this research, we used histological sections to study tissue reaction to LPSPs (4.4-microm median diameter) when used for sciatic nerve block in the rat. As a reference, we compared LPSPs to 60-microm median diameter poly(lactic-co-glycolic) acid (PLGA) microspheres (110,000 MW PLGA, glycolic/lactic ratio 65:35). Four days after injection, both particle types produced acute inflammation within the confines of the injectate, inflammation in adjacent tissues, and myotoxicity. Bupivacaine-free particles did not display myotoxicity, and inflammation in adjacent tissues was reduced. At 2 weeks, inflammation from LPSPs had almost disappeared, whereas PLGA microspheres had a foreign-body giant cell reaction until at least 8 weeks after injection. In contrast, 3.6-microm median diameter, 20,000-MW PLGA microspheres produced a primarily histiocytic reaction 2 weeks after injection. In summary, the LPSPs and PLGA microspheres studied herein have excellent biocompatibility, but tissue reaction to the former is of much shorter duration. Myotoxicity and inflammation of surrounding tissue is largely attributed to bupivacaine. Foreign-body giant cells may be attributed to particle size rather than a specific reaction to PLGA.
authors.affiliation: Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kohane
authors.forename: Michael
authors.initials: M
authors.lastname: Lipp
authors.forename: Ramsey C
authors.initials: RC
authors.lastname: Kinney
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Anthony
authors.forename: David N
authors.initials: DN
authors.lastname: Louis
authors.forename: Noah
authors.initials: N
authors.lastname: Lotan
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D002045:Bupivacaine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D016503:Drug Delivery Systems / Q000379:methods / Q000592:standards; D007249:Inflammation / Q000139:chemically induced; D019344:Lactic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D007785:Lactose / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D008297:Male; D008863:Microspheres; D009407:Nerve Block / Q000379:methods; D010525:Peripheral Nerves / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve; D012709:Serum Albumin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D011108:Polymers; D012709:Serum Albumin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D015060:1,2-Dipalmitoylphosphatidylcholine; D019344:Lactic Acid; D007785:Lactose; D002045:Bupivacaine