alexa Prolonged duration local anesthesia with lipid-protein-sugar particles containing bupivacaine and dexamethasone.


Lupus: Open Access

Author(s): Colombo G, Padera R, Langer R, Kohane DS

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Abstract Glucocorticoids prolong block duration from polymeric microspheres containing bupivacaine, but not from unencapsulated drug. Here we investigate this effect applies to particles with much more rapid drug release and improved long-term biocompatibility. Male Sprague-Dawley rats were given sciatic nerve blocks with 75 mg of 3\% or 60\% (w/w) dipalmitoylphosphatidylcholine (DPPC) spray-dried lipid-protein-sugar particles (LPSPs) containing 10\% (w/w) bupivacaine and 0\%, 0.05\%, or 0.1\% (w/w) dexamethasone. Sensory nerve block from bupivacaine-containing 3\% and 60\% (w/w) DPPC particles without dexamethasone yielded blocks lasting 301 +/- 56 and 321 +/- 127 min, respectively. Addition of 0.05\% (w/w) dexamethasone increased block durations to 610 +/- 182 and 538 +/- 222 min, respectively; increasing dexamethasone loading to 0.1\% did not further increase duration. One day after injection, dexamethasone-containing particles resulted in lower inflammation scores and capsule thickness than dexamethasone-free particles, but the difference was gone by day 4. Excipient composition had prominent effects at all time points. For all groups, inflammation was largely resolved by 2 weeks after injection. Dexamethasone approximately doubled the duration of nerve block from bupivacaine-loaded LPSPs, while maintaining excellent biocompatibility. Such formulations could be useful in clinical applications when nerve blockade is needed for 24 hours or less. This article was published in J Biomed Mater Res A and referenced in Lupus: Open Access

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