Kohane D S, Lipp M, Kinney R C, Lotan N, Langer R
Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Pharm Res. 2000 Oct;17(10):1243-9. doi: 10.1023/a:1026470831256.
To assess the efficacy of lipid-protein-sugar particles (LPSPs) in providing prolonged duration local anesthesia by percutaneous injection.
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.
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.
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.
评估脂质 - 蛋白质 - 糖颗粒(LPSPs)经皮注射提供长效局部麻醉的效果。
对含布比卡因的LPSPs进行体外特性鉴定和优化。给雄性Sprague-Dawley大鼠坐骨神经注射含布比卡因的LPSPs进行阻滞。测量后爪的感觉和运动神经阻滞情况,以及对侧功能缺陷(衡量全身药物分布的指标)。使用聚乳酸 - 乙醇酸共聚物(PLGA)微球作为对照。
10%(w/w)布比卡因LPSPs(60%二棕榈酰磷脂酰胆碱)直径为4.4±0.39微米,振实密度为0.11±0.04克/毫升。这些LPSPs和50%(w/w)PLGA微球的感觉阻滞持续时间相当(468±210分钟对706±344分钟,p = 0.08),尽管LPSPs产生的运动阻滞持续时间短得多(508±258分钟对1062±456分钟,p = 0.005)。两组的全身毒性均最小。
LPSPs提供的感觉阻滞持续时间与PLGA微球相当,但药物负载量较少。LPSPs的运动阻滞时间比PLGA微球短。LPSPs似乎适用于延长神经阻滞。鉴于其大小和低密度,它们可能对气道局部麻醉有用。