Purpose. To investigate whether decreasing the phospholipidic fraction in lipid-protein-sugar particles (LPSPs), designed to achieve prolonged duration local anesthesia, can reduce tissue reaction without compromising the duration of nerve block. Methods. Bupivacaine-loaded LPSPs were prepared by spray drying an ethanol:water mixture containing albumin, α-lactose, dipalmitoyl-phosphatidylcholine (DPPC, 3% or 60% w/w) and bupivacaine. Drug loading was assessed. Duration of block was measured in rats following sciatic nerve injection. One, 4 and 14 days after the injection, nerves were harvested for histology, together with adherent tissues. Results. 60% and 3% DPPC particles had 7.18 ± 0.47% and 7.21 ± 0.94% bupivacaine loading, respectively. Sensory and motor block from 3% DPPC lasted 301 ± 56 minutes and 412 ± 173 minutes. Corresponding data for 60% DPPC particles were 321 ± 127 and 513 ± 216 minutes with no statistically significant difference between formulations. On gross dissection, pockets of particles were not detectable in any animal receiving 3% DPPC particles. However, they were detected in all animals receiving 60% DPPC particles 1 day after injection, 2 of 4 rats at 4 days, none at 14 days. All animals showed an acute inflammatory response with neutrophils at 1 day after injection; at 4 days, the rats receiving the 60% DPPC particles still showed acute inflammation, while 3% DPPC particles led to a milder tissue reaction with more mononuclear cells. At 14 days, both groups showed a mild mononuclear reaction. Conclusion. The two formulations containing the same loading of bupivacaine but different amounts of DPPC demonstrated equivalent durations of block. The 3% DPPC formulation had a shorter tissue dwell time and milder tissue reaction than the 60% formulation.
Efficacy and biocompatibility of bupivacaine-loaded lipid-protein-sugar particles for prolonged duration local anesthesia
COLOMBO, Gaia;
2002
Abstract
Purpose. To investigate whether decreasing the phospholipidic fraction in lipid-protein-sugar particles (LPSPs), designed to achieve prolonged duration local anesthesia, can reduce tissue reaction without compromising the duration of nerve block. Methods. Bupivacaine-loaded LPSPs were prepared by spray drying an ethanol:water mixture containing albumin, α-lactose, dipalmitoyl-phosphatidylcholine (DPPC, 3% or 60% w/w) and bupivacaine. Drug loading was assessed. Duration of block was measured in rats following sciatic nerve injection. One, 4 and 14 days after the injection, nerves were harvested for histology, together with adherent tissues. Results. 60% and 3% DPPC particles had 7.18 ± 0.47% and 7.21 ± 0.94% bupivacaine loading, respectively. Sensory and motor block from 3% DPPC lasted 301 ± 56 minutes and 412 ± 173 minutes. Corresponding data for 60% DPPC particles were 321 ± 127 and 513 ± 216 minutes with no statistically significant difference between formulations. On gross dissection, pockets of particles were not detectable in any animal receiving 3% DPPC particles. However, they were detected in all animals receiving 60% DPPC particles 1 day after injection, 2 of 4 rats at 4 days, none at 14 days. All animals showed an acute inflammatory response with neutrophils at 1 day after injection; at 4 days, the rats receiving the 60% DPPC particles still showed acute inflammation, while 3% DPPC particles led to a milder tissue reaction with more mononuclear cells. At 14 days, both groups showed a mild mononuclear reaction. Conclusion. The two formulations containing the same loading of bupivacaine but different amounts of DPPC demonstrated equivalent durations of block. The 3% DPPC formulation had a shorter tissue dwell time and milder tissue reaction than the 60% formulation.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
