DRV Liposomal Bupivacaine: Preparation, Characterization, and In Vivo Evaluation in Mice

@article{citeulike:2516539, abstract = {Purpose. To evaluate the dehydration-rehydration technique to prepare a formulation of liposomal bupivacaine, and to assess its analgesic efficacy.Methods. Bupivacaine hydrochloride (BUP) was encapsulated into dehydration-rehydration vesicles (DRV) of varying phospholipid (PL) compositions. Two bilayer-forming phospholipids were used, the “fluid” dimyristoyl-phosphatidylcholine and the “solid” dis- tearoyl-phosphatidylcholine (DSPC), with 20 or 40 mol\% cholesterol, in the presence of bupivacaine at a 1.28 or 0.64 BUP/PL mole ratio. After rehydration, drug/lipid ratios were determined. The formulation with the highest drug/lipid ratio (DSPC/cholesterol in an 8:2 mole ratio prepared in the presence of bupivacaine in a 1.28 BUP/PL mole ratio) was adjusted to a final bupivacaine concentration of 3.5\% or 0.5\%. The duration of skin analgesia after subcutaneous injection in mice produced by these formulations was compared with the conventional administration of a plain 0.5\% solution of BUP. In addition, the concentration of residual bupivacaine at the injection site was followed for 96 h.Results. The relatively low organic solvent/aqueous phase and membrane/aqueous phase partition coefficients, together with liposomal trapped volume and BUP/PL mole ratio, indicated that most of the drug was encapsulated in the intraliposome aqueous phase of the DRV. The DSPC/cholesterol 8:2 mole ratio had the best drug encapsulation (BUP/PL = 0.36). Compared to plain BUP, these BUP-DRV produced significant prolongation of analgesia, which is explained by longer residence time of the drug at the site of injection.Conclusions. Bupivacaine-DRV may have a role in achieving safe, effective, and prolonged analgesia in humans.}, author = {Grant}, citeulike-article-id = {2516539}, journal = {Pharm. Res.}, keywords = {bupivacaine, chronic\_pain, drug\_delivery, liposomes, mouse\_model}, month = {March}, number = {3}, pages = {336--343}, posted-at = {2008-03-11 20:32:15}, priority = {2}, title = {DRV Liposomal Bupivacaine: Preparation, Characterization, and In Vivo Evaluation in Mice}, url = {http://www.ingentaconnect.com/content/klu/pham/2001/00000018/00000003/00299795}, volume = {18}, year = {2001} }

TY - JOUR ID - citeulike:2516539 L3 - citeulike-article-id:2516539 TI - DRV Liposomal Bupivacaine: Preparation, Characterization, and In Vivo Evaluation in Mice JF - Pharm. Res. VL - 18 IS - 3 SP - 336 EP - 343 N2 - Purpose. To evaluate the dehydration-rehydration technique to prepare a formulation of liposomal bupivacaine, and to assess its analgesic efficacy.Methods. Bupivacaine hydrochloride (BUP) was encapsulated into dehydration-rehydration vesicles (DRV) of varying phospholipid (PL) compositions. Two bilayer-forming phospholipids were used, the “fluid” dimyristoyl-phosphatidylcholine and the “solid” dis- tearoyl-phosphatidylcholine (DSPC), with 20 or 40 mol% cholesterol, in the presence of bupivacaine at a 1.28 or 0.64 BUP/PL mole ratio. After rehydration, drug/lipid ratios were determined. The formulation with the highest drug/lipid ratio (DSPC/cholesterol in an 8:2 mole ratio prepared in the presence of bupivacaine in a 1.28 BUP/PL mole ratio) was adjusted to a final bupivacaine concentration of 3.5% or 0.5%. The duration of skin analgesia after subcutaneous injection in mice produced by these formulations was compared with the conventional administration of a plain 0.5% solution of BUP. In addition, the concentration of residual bupivacaine at the injection site was followed for 96 h.Results. The relatively low organic solvent/aqueous phase and membrane/aqueous phase partition coefficients, together with liposomal trapped volume and BUP/PL mole ratio, indicated that most of the drug was encapsulated in the intraliposome aqueous phase of the DRV. The DSPC/cholesterol 8:2 mole ratio had the best drug encapsulation (BUP/PL = 0.36). Compared to plain BUP, these BUP-DRV produced significant prolongation of analgesia, which is explained by longer residence time of the drug at the site of injection.Conclusions. Bupivacaine-DRV may have a role in achieving safe, effective, and prolonged analgesia in humans. KW - bupivacaine KW - chronic_pain KW - drug_delivery KW - liposomes KW - mouse_model AU - Grant PY - 2001/03// UR - http://www.ingentaconnect.com/content/klu/pham/2001/00000018/00000003/00299795 ER -