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

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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.

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Authors and Affiliations

  1. Department of Anesthesiology, New York University School of Medicine, 550 First Avenue, New York, New York, 10016

    Gilbert J. Grant, Boris Piskoun, Mylarrao Bansinath, Herman Turndorf & Elijah M. Bolotin

  2. Laboratory of Membrane and Liposome Research, Department of Biochemistry, The Hebrew University-Hadassah Medical School, P.O.B. 12272, Jerusalem, 91120, Israel

    Yechezkel Barenholz

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  1. Gilbert J. Grant
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  2. Yechezkel Barenholz
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  4. Mylarrao Bansinath
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  5. Herman Turndorf
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  6. Elijah M. Bolotin
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Grant, G.J., Barenholz, Y., Piskoun, B. et al. DRV Liposomal Bupivacaine: Preparation, Characterization, and In Vivo Evaluation in Mice. Pharm Res 18, 336–343 (2001). https://doi.org/10.1023/A:1011059131348

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