Purpose: Bupivacaine-loaded lipid-protein-sugar particles (LPSPs) can provide prolonged duration local anesthesia. Here, we examine the effect of composition on LPSPs long-term biocompatibility. We also investigate whether the block-prolonging effects of dexamethasone, seen for other local anesthetic-loaded microparticles, apply to LPSPs. Methods: Male Sprague-Dawley rats were given sciatic nerve blocks with 75 mg of 3 or 60% (w/w) dipalmitoyl-phosphatidylcholine (DPPC) spray-dried LPSPs containing 10% (w/w) bupivacaine and 0, 0.05, or 0.1% (w/w) dexamethasone. Neurobehavioral testing was performed to evaluate block duration. Nerves were harvested to assess biocompatibility. Results: Dexamethasone-free LPSPs produced sensory blocks lasting 301 ± 56 and 321 ± 127 min for 3 and 60% (w/w) DPPC particles, respectively, with no significant difference. However, large particle debris and acute inflammation were seen in animals receiving the more hydrophobic formulation at 1 and 4 days after injection, whereas only mild inflammation occurred in the 3% DPPC group. When 0.05% (w/w) dexamethasone was added, durations of block increased to 610 ± 182 and 538 ± 222 min, respectively. Higher dexamethasone resulted in no further improvement. Dexamethasone reduced inflammation at day 1 in both groups. In all cases, inflammation was largely resolved by two weeks. Conclusions: Reduction in DPPC content greatly improved the biocompatibility of bupivacaine-loaded LPSPs, without affecting duration of block. Dexamethasone almost doubled the duration of nerve block, while maintaining particles’ excellent biocompatibility.
Prolonged duration local anesthesia with lipid-protein-sugar particles containing bupivacaine and dexamethasone
COLOMBO, Gaia;
2004
Abstract
Purpose: Bupivacaine-loaded lipid-protein-sugar particles (LPSPs) can provide prolonged duration local anesthesia. Here, we examine the effect of composition on LPSPs long-term biocompatibility. We also investigate whether the block-prolonging effects of dexamethasone, seen for other local anesthetic-loaded microparticles, apply to LPSPs. Methods: Male Sprague-Dawley rats were given sciatic nerve blocks with 75 mg of 3 or 60% (w/w) dipalmitoyl-phosphatidylcholine (DPPC) spray-dried LPSPs containing 10% (w/w) bupivacaine and 0, 0.05, or 0.1% (w/w) dexamethasone. Neurobehavioral testing was performed to evaluate block duration. Nerves were harvested to assess biocompatibility. Results: Dexamethasone-free LPSPs produced sensory blocks lasting 301 ± 56 and 321 ± 127 min for 3 and 60% (w/w) DPPC particles, respectively, with no significant difference. However, large particle debris and acute inflammation were seen in animals receiving the more hydrophobic formulation at 1 and 4 days after injection, whereas only mild inflammation occurred in the 3% DPPC group. When 0.05% (w/w) dexamethasone was added, durations of block increased to 610 ± 182 and 538 ± 222 min, respectively. Higher dexamethasone resulted in no further improvement. Dexamethasone reduced inflammation at day 1 in both groups. In all cases, inflammation was largely resolved by two weeks. Conclusions: Reduction in DPPC content greatly improved the biocompatibility of bupivacaine-loaded LPSPs, without affecting duration of block. Dexamethasone almost doubled the duration of nerve block, while maintaining particles’ excellent biocompatibility.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
