塞来昔布固体脂质纳米粒的制备及其在大鼠体内的药动学

目的:制备塞来昔布固体脂质纳米粒,并考察大鼠灌胃给药后体内的药动学特征。方法:采用热熔乳化超声-低温固化法制备塞来昔布固体脂质纳米粒,并对制得的纳米粒进行表征。将12只Wistar大鼠随机分为为塞来昔布原料药组和塞来昔布固体脂质纳米粒组,灌胃给药剂量均为100 mg·kg^-1,采用高效液相色谱法测定大鼠血浆中塞来昔布的浓度,采用3P97程序计算塞来昔布药动学参数。结果:塞来昔布固体脂质纳米粒平均粒径为(183.6±44.5)nm,PdI为(0.217±0.052),Zeta电位为(-30.4±5.2)mV。塞来昔布原料药和塞来昔布固体脂质纳米粒在大鼠体内的AUC_(0-t)分别为(4.47±0.72)和(11.64±2.01)mg·L^-1·h;t_1/2分别为(13.45±1.89)和(10.12±1.24)h;t_max 分别为(2.33±0.21)和(1.31±0.14)h;C_max分别为(0.86±0.12)和(2.14±0.46 )mg·L^-1。结论:塞来昔布固体脂质纳米粒能够明显改善大鼠体内塞来昔布的药动学行为,与塞来昔布原料药相比具有明显的缓释效果,同时提高了药物的生物利用度。

Preparation of celecoxib solid lipid nanoparticles and its pharmacokinetic behaviors in rats

OBJECTIVE To prepare celecoxib (CXB) solid lipid nanoparticle (CXB-SLN) and study the pharmacokinetic behaviors of CXB-SLN in rats. METHODS CXB-SLN was prepared by melt-emulsion ultrasonication and low temperature-solidification methods. The CXB-SLN was characterized. 12 Wistar rats were randomly divided into CXB API group and CXB-SLN group, and gavaged at a dose of 100 mg·kg^-1. HPLC was used to determined Plasma CXB concentration, and 3P97 program to calculate pharmacokinetic parameters. RESULTS For particle size, polydispersion index and Zeta potential of CXB-SLN were (183.6±44.5)nm, (0.217±0.052) and (-30.4±5.2) mV, respectively. For CXB API and CXB-SLN, AUC_0-t values were (4.47±0.72) and (11.64±2.01) mg·L^-1·h, t_1/2 were (13.45±1.89) and (10.12±1.24) h, t_max were (2.33±0.21) and (1.31±0.14) h,C_max were (0.86±0.12) and (2.14±0.46) mg·L^-1, respectively. CONCLUSION Compared to CXB API, CXB-SLN has significantly improved pharmacokinetic behaviors, obviously delayed release and improved bioavailability in rats.