Effect of excipient composition on the biocompatibility of bupivacaine-containing microparticles at the sciatic nerve.
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-microm diameter) and 60% (4.7-microm 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.
Pharmaceutical Department, University of Parma, Parma, Italy.
Gaia
G
Colombo
Robert
R
Langer
Daniel S
DS
Kohane
D000818:Animals; D001672:Biocompatible Materials; D002045:Bupivacaine; D005079:Excipients; D008297:Male; D008863:Microspheres; D009407:Nerve Block; D051381:Rats; D012584:Sciatic Nerve / Q000502:physiology*; D013997:Time Factors
D001672:Biocompatible Materials; D005079:Excipients; D002045:Bupivacaine