A novel liposomal bupivacaine formulation to produce ultralong-acting analgesia. Grant, G., J., Barenholz, Y., Bolotin, E., M., Bansinath, M., Turndorf, H., Piskoun, B., & Davidson, E., M. Anesthesiology, 101(1):133-137, 2004. ![A novel liposomal bupivacaine formulation to produce ultralong-acting analgesia. [pdf]](https://bibbase.org/img/filetypes/pdf.svg "pdf")
Paper abstract bibtex BACKGROUND: Currently available local anesthetics have relatively brief durations of action. An ultralong-acting local anesthetic would benefit patients with acute and chronic pain. The authors prepared and characterized a novel liposomal bupivacaine formulation using remote loading of bupivacaine along an ammonium sulfate gradient and assessed its efficacy in humans. METHODS: A large multivesicular liposomal bupivacaine formulation was prepared by subjecting small unilamellar vesicles to successive freeze-and-thaw cycles. Bupivacaine hydrochloride was then remotely loaded into the liposomes along an ammonium sulfate gradient ([(NH4)2SO4)]intraliposome/[(NH4)2SO4)]medium > 1000). The liposomes were then characterized for size distribution; drug-to-phospholipid ratio; in vitro release profile at 4 degree, 21 degree C, and 37 degree C; sterility; and pyrogenicity. Six subjects each received six intradermal injections in the lower back with 0.5 ml of 0.5, 1.0, and 2% liposomal bupivacaine; 0.5% standard bupivacaine; saline; and "empty" liposomes. Duration of analgesia was assessed using pinprick testing of the skin directly over the injection sites. Results were compared using the log-rank test. RESULTS: The mean large multivesicular vesicle size was 2439 +/- 544 nm, with a drug-to-phospholipid ratio of 1.8, fivefold greater than results previously reported. In vitro release was slowest at 4 degree C. The median duration of analgesia with 0.5% standard bupivacaine was 1 h. The median durations of analgesia after 0.5, 1.0, and 2.0% liposomal bupivacaine were 19, 38, and 48 h, respectively. Neither saline nor "empty" liposomes produced analgesia. CONCLUSIONS: This novel liposomal formulation had a favorable drug-to-phospholipid ratio and prolonged the duration of bupivacaine analgesia in a dose-dependent manner. If these results in healthy volunteers can be duplicated in the clinical setting, this formulation has the potential to significantly impact the management of pain.
@article{
title = {A novel liposomal bupivacaine formulation to produce ultralong-acting analgesia.},
type = {article},
year = {2004},
identifiers = {[object Object]},
pages = {133-137},
volume = {101},
id = {92cfd769-4584-3373-9995-7a0280f5c786},
created = {2017-02-10T12:46:12.000Z},
file_attached = {true},
profile_id = {2098c724-2791-3f45-886e-d4d234659211},
group_id = {13155ea3-49f2-3ba8-9035-c42432975e62},
last_modified = {2017-02-10T12:46:15.000Z},
read = {false},
starred = {false},
authored = {false},
confirmed = {true},
hidden = {false},
citation_key = {Grant2004},
abstract = {BACKGROUND: Currently available local anesthetics have relatively brief durations of action. An ultralong-acting local anesthetic would benefit patients with acute and chronic pain. The authors prepared and characterized a novel liposomal bupivacaine formulation using remote loading of bupivacaine along an ammonium sulfate gradient and assessed its efficacy in humans. METHODS: A large multivesicular liposomal bupivacaine formulation was prepared by subjecting small unilamellar vesicles to successive freeze-and-thaw cycles. Bupivacaine hydrochloride was then remotely loaded into the liposomes along an ammonium sulfate gradient ([(NH4)2SO4)]intraliposome/[(NH4)2SO4)]medium > 1000). The liposomes were then characterized for size distribution; drug-to-phospholipid ratio; in vitro release profile at 4 degree, 21 degree C, and 37 degree C; sterility; and pyrogenicity. Six subjects each received six intradermal injections in the lower back with 0.5 ml of 0.5, 1.0, and 2% liposomal bupivacaine; 0.5% standard bupivacaine; saline; and "empty" liposomes. Duration of analgesia was assessed using pinprick testing of the skin directly over the injection sites. Results were compared using the log-rank test. RESULTS: The mean large multivesicular vesicle size was 2439 +/- 544 nm, with a drug-to-phospholipid ratio of 1.8, fivefold greater than results previously reported. In vitro release was slowest at 4 degree C. The median duration of analgesia with 0.5% standard bupivacaine was 1 h. The median durations of analgesia after 0.5, 1.0, and 2.0% liposomal bupivacaine were 19, 38, and 48 h, respectively. Neither saline nor "empty" liposomes produced analgesia. CONCLUSIONS: This novel liposomal formulation had a favorable drug-to-phospholipid ratio and prolonged the duration of bupivacaine analgesia in a dose-dependent manner. If these results in healthy volunteers can be duplicated in the clinical setting, this formulation has the potential to significantly impact the management of pain.},
bibtype = {article},
author = {Grant, Gilbert J and Barenholz, Yechezkel and Bolotin, Elijah M and Bansinath, Mylarrao and Turndorf, Herman and Piskoun, Boris and Davidson, Elyad M},
journal = {Anesthesiology},
number = {1}
}
Downloads: 0
{"_id":"EXCW6MztfdRWimwMs","bibbaseid":"grant-barenholz-bolotin-bansinath-turndorf-piskoun-davidson-anovelliposomalbupivacaineformulationtoproduceultralongactinganalgesia-2004","downloads":0,"creationDate":"2017-02-24T11:31:37.428Z","title":"A novel liposomal bupivacaine formulation to produce ultralong-acting analgesia.","author_short":["Grant, G., J.","Barenholz, Y.","Bolotin, E., M.","Bansinath, M.","Turndorf, H.","Piskoun, B.","Davidson, E., M."],"year":2004,"bibtype":"article","biburl":null,"bibdata":{"title":"A novel liposomal bupivacaine formulation to produce ultralong-acting analgesia.","type":"article","year":"2004","identifiers":"[object Object]","pages":"133-137","volume":"101","id":"92cfd769-4584-3373-9995-7a0280f5c786","created":"2017-02-10T12:46:12.000Z","file_attached":"true","profile_id":"2098c724-2791-3f45-886e-d4d234659211","group_id":"13155ea3-49f2-3ba8-9035-c42432975e62","last_modified":"2017-02-10T12:46:15.000Z","read":false,"starred":false,"authored":false,"confirmed":"true","hidden":false,"citation_key":"Grant2004","abstract":"BACKGROUND: Currently available local anesthetics have relatively brief durations of action. An ultralong-acting local anesthetic would benefit patients with acute and chronic pain. The authors prepared and characterized a novel liposomal bupivacaine formulation using remote loading of bupivacaine along an ammonium sulfate gradient and assessed its efficacy in humans. METHODS: A large multivesicular liposomal bupivacaine formulation was prepared by subjecting small unilamellar vesicles to successive freeze-and-thaw cycles. Bupivacaine hydrochloride was then remotely loaded into the liposomes along an ammonium sulfate gradient ([(NH4)2SO4)]intraliposome/[(NH4)2SO4)]medium > 1000). The liposomes were then characterized for size distribution; drug-to-phospholipid ratio; in vitro release profile at 4 degree, 21 degree C, and 37 degree C; sterility; and pyrogenicity. Six subjects each received six intradermal injections in the lower back with 0.5 ml of 0.5, 1.0, and 2% liposomal bupivacaine; 0.5% standard bupivacaine; saline; and \"empty\" liposomes. Duration of analgesia was assessed using pinprick testing of the skin directly over the injection sites. Results were compared using the log-rank test. RESULTS: The mean large multivesicular vesicle size was 2439 +/- 544 nm, with a drug-to-phospholipid ratio of 1.8, fivefold greater than results previously reported. In vitro release was slowest at 4 degree C. The median duration of analgesia with 0.5% standard bupivacaine was 1 h. The median durations of analgesia after 0.5, 1.0, and 2.0% liposomal bupivacaine were 19, 38, and 48 h, respectively. Neither saline nor \"empty\" liposomes produced analgesia. CONCLUSIONS: This novel liposomal formulation had a favorable drug-to-phospholipid ratio and prolonged the duration of bupivacaine analgesia in a dose-dependent manner. If these results in healthy volunteers can be duplicated in the clinical setting, this formulation has the potential to significantly impact the management of pain.","bibtype":"article","author":"Grant, Gilbert J and Barenholz, Yechezkel and Bolotin, Elijah M and Bansinath, Mylarrao and Turndorf, Herman and Piskoun, Boris and Davidson, Elyad M","journal":"Anesthesiology","number":"1","bibtex":"@article{\n title = {A novel liposomal bupivacaine formulation to produce ultralong-acting analgesia.},\n type = {article},\n year = {2004},\n identifiers = {[object Object]},\n pages = {133-137},\n volume = {101},\n id = {92cfd769-4584-3373-9995-7a0280f5c786},\n created = {2017-02-10T12:46:12.000Z},\n file_attached = {true},\n profile_id = {2098c724-2791-3f45-886e-d4d234659211},\n group_id = {13155ea3-49f2-3ba8-9035-c42432975e62},\n last_modified = {2017-02-10T12:46:15.000Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Grant2004},\n abstract = {BACKGROUND: Currently available local anesthetics have relatively brief durations of action. An ultralong-acting local anesthetic would benefit patients with acute and chronic pain. The authors prepared and characterized a novel liposomal bupivacaine formulation using remote loading of bupivacaine along an ammonium sulfate gradient and assessed its efficacy in humans. METHODS: A large multivesicular liposomal bupivacaine formulation was prepared by subjecting small unilamellar vesicles to successive freeze-and-thaw cycles. Bupivacaine hydrochloride was then remotely loaded into the liposomes along an ammonium sulfate gradient ([(NH4)2SO4)]intraliposome/[(NH4)2SO4)]medium > 1000). The liposomes were then characterized for size distribution; drug-to-phospholipid ratio; in vitro release profile at 4 degree, 21 degree C, and 37 degree C; sterility; and pyrogenicity. Six subjects each received six intradermal injections in the lower back with 0.5 ml of 0.5, 1.0, and 2% liposomal bupivacaine; 0.5% standard bupivacaine; saline; and \"empty\" liposomes. Duration of analgesia was assessed using pinprick testing of the skin directly over the injection sites. Results were compared using the log-rank test. RESULTS: The mean large multivesicular vesicle size was 2439 +/- 544 nm, with a drug-to-phospholipid ratio of 1.8, fivefold greater than results previously reported. In vitro release was slowest at 4 degree C. The median duration of analgesia with 0.5% standard bupivacaine was 1 h. The median durations of analgesia after 0.5, 1.0, and 2.0% liposomal bupivacaine were 19, 38, and 48 h, respectively. Neither saline nor \"empty\" liposomes produced analgesia. CONCLUSIONS: This novel liposomal formulation had a favorable drug-to-phospholipid ratio and prolonged the duration of bupivacaine analgesia in a dose-dependent manner. If these results in healthy volunteers can be duplicated in the clinical setting, this formulation has the potential to significantly impact the management of pain.},\n bibtype = {article},\n author = {Grant, Gilbert J and Barenholz, Yechezkel and Bolotin, Elijah M and Bansinath, Mylarrao and Turndorf, Herman and Piskoun, Boris and Davidson, Elyad M},\n journal = {Anesthesiology},\n number = {1}\n}","author_short":["Grant, G., J.","Barenholz, Y.","Bolotin, E., M.","Bansinath, M.","Turndorf, H.","Piskoun, B.","Davidson, E., M."],"urls":{"Paper":"http://bibbase.org/service/mendeley/2098c724-2791-3f45-886e-d4d234659211/file/1aaa06a0-f18b-c837-7465-79c2059e2d03/2004-A_novel_liposomal_bupivacaine_formulation_to_produce_ultralong-acting_analgesia..pdf.pdf"},"bibbaseid":"grant-barenholz-bolotin-bansinath-turndorf-piskoun-davidson-anovelliposomalbupivacaineformulationtoproduceultralongactinganalgesia-2004","role":"author","downloads":0},"search_terms":["novel","liposomal","bupivacaine","formulation","produce","ultralong","acting","analgesia","grant","barenholz","bolotin","bansinath","turndorf","piskoun","davidson"],"keywords":[],"authorIDs":[]}