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EnglishMicroparticulate formulations are often used for experimental prolongation of nerve blockade. Here we examine the effect of excipient composition on the biocompatibility of bupivacaine-containing microparticles. Lipid-protein- sugar particles (LPSPs) composed of 3% (1.3 micron diameter) and 60% (4.7 micron diameter) (w/w) dipalmitoylphosphatidylcholine (DPPC) were produced by spray drying, containing 10% (w/w) bupivacaine. Rat sciatic nerve blocks with 75 mg of particles produced statistically similar durations of sensory nerve block [3% (w/w) DPPC particles: 301 min; 60% (w/w) DPPC particles: 321 min]. Examination of tissues 1 day after injection revealed large particle deposits and acute inflammation in animals that received 60% (w/w) DPPC particles. There were no visible deposits in those that received 3% (w/w) DPPC particles, and microscopic inflammation was reduced. The difference between groups was similar 4 days after injection. Two weeks after injection, there was no particulate mass in either group, and inflammation had largely resolved. In both groups, moderately severe myotoxicity was seen 1 and 4 days after injection but had largely resolved by 2 weeks. In summary, reduction in particles’ DPPC content greatly improved biocompatibility without compromising duration of nerve blockade; the improvement was probably attributable to the enhanced rate of particle resorption.
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| Data di pubblicazione: | 2004 | |
| Titolo: | Effect of excipient composition on the biocompatibility of bupivacaine-containing microparticles at the sciatic nerve | |
| Autori: | G. COLOMBO; R. LANGER; D.S. KOHANE | |
| Rivista: | JOURNAL OF BIOMEDICAL MATERIALS RESEARCH. PART A | |
| Parole Chiave: | Prolonged duration local anesthesia; Controlled release; Epineurium; Inflammation; Myotoxicity | |
| Abstract: | Microparticulate formulations are often used for experimental prolongation of nerve blockade. Here we examine the effect of excipient composition on the biocompatibility of bupivacaine-containing microparticles. Lipid-protein- sugar particles (LPSPs) composed of 3% (1.3 micron diameter) and 60% (4.7 micron diameter) (w/w) dipalmitoylphosphatidylcholine (DPPC) were produced by spray drying, containing 10% (w/w) bupivacaine. Rat sciatic nerve blocks with 75 mg of particles produced statistically similar durations of sensory nerve block [3% (w/w) DPPC particles: 301 min; 60% (w/w) DPPC particles: 321 min]. Examination of tissues 1 day after injection revealed large particle deposits and acute inflammation in animals that received 60% (w/w) DPPC particles. There were no visible deposits in those that received 3% (w/w) DPPC particles, and microscopic inflammation was reduced. The difference between groups was similar 4 days after injection. Two weeks after injection, there was no particulate mass in either group, and inflammation had largely resolved. In both groups, moderately severe myotoxicity was seen 1 and 4 days after injection but had largely resolved by 2 weeks. In summary, reduction in particles’ DPPC content greatly improved biocompatibility without compromising duration of nerve blockade; the improvement was probably attributable to the enhanced rate of particle resorption. | |
| Digital Object Identifier (DOI): | 10.1002/jbm.a.20074 | |
| Handle: | http://hdl.handle.net/11392/1199000 | |
| Appare nelle tipologie: | 03.1 Articolo su rivista |
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