Sciatic nerve blockade with lipid-protein-sugar particles containing bupivacaine.
OBJECTIVE
To assess the efficacy of lipid-protein-sugar particles (LPSPs) in providing prolonged duration local anesthesia by percutaneous injection.


METHODS
Bupivacaine-containing LPSPs were characterized and optimized in vitro. Male Sprague-Dawley rats were given sciatic nerve blocks with bupivacaine-containing LPSPs. Sensory and motor nerve blockade were measured in the hindpaw, as were contralateral functional deficits (a measure of systemic drug distribution). Poly(lactic-co-glycolic) acid (PLGA) microspheres were used as a reference.


RESULTS
10% (w/w) bupivacaine LPSPs (60% dipalmitoylphosphatidylcholine) were 4.4+/-0.39 microm in diameter, with a tap density of 0.11 +/-0.04 g/ml. These LPSPs and 50% (w/w) PLGA microspheres had comparable durations of sensory blockade (468+/-210 min vs. 706+/-344 min, p = 0.08), although the LPSPs produced a much lesser duration of motor blockade (508+/-258 min vs. 1062+/-456 min, p = 0.005). Systemic toxicity was minimal in both groups.


CONCLUSIONS
LPSPs provide sensory blockade durations comparable to those from PLGA microspheres, with a smaller amount of drug loading. Motor blockade is shorter with LPSPs than with PLGA microspheres. LPSPs appear to be suitable for extended nerve blockade. Given their size and low density, they may be useful for topical anesthesia of the airway.
Kohane
D S
DS
Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Lipp
M
M
Kinney
R C
RC
Lotan
N
N
Langer
R
R
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000008:administration & dosage* / Q000737:chemistry; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D007785:Lactose / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008863:Microspheres; D009407:Nerve Block; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve; D012709:Serum Albumin / Q000008:administration & dosage* / Q000737:chemistry
D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; D012709:Serum Albumin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D015060:1,2-Dipalmitoylphosphatidylcholine; D019344:Lactic Acid; D007785:Lactose; D002045:Bupivacaine