尼莫地平固体脂质纳米粒的制备及其体外透皮特性研究

Study on Preparation and in Vitro Percutaneous Permeability of Solid Lipid Nanoparticles Loaded with Nimodipine

目的研制尼莫地平固体脂质纳米粒,并考察其理化性质及体外透皮特性。方法采用熔融超声-低温固化法制备尼莫地平固体脂质纳米粒,考察其形态、粒径、粒度分布、Zeta电位等理化性质,以RP-HPLC测定药物的包封率和载药量,以改良的Franz扩散装置研究其体外释药和透皮扩散特性。结果优化条件下制备的尼莫地平固体脂质纳米粒均匀圆整,平均粒径为(104.47±3.98)nm,跨距为(0.96±0.04),包封率为(95.53±1.15)%,载药量为(9.22±0.12)%,Zeta电位为-(34.3±5.1)mV;体外药物呈缓释释放,符合Higuchi动力学模型:Q=0.1156t1/2-0.1373(r2=0.9905);体外透皮特性优于氮酮、油酸和丁香油对尼莫地平的促透作用。结论尼莫地平固体脂质纳米粒处方和工艺合理可靠,经皮渗透特性较佳,作为药物微载体可用于多种经皮给药系统的设计。

OBJECTIVE To prepare nimodipine-loaded solid lipid nanoparficles（NIM-SLN） and investigate their physico-chemical properties and percutaneous permeability through excised SD rat skin in vitro. METHODS NIM-SLN were prepared using the hot dispersion-cool solidification method. The morphology, mean diameter, size distribution and Zeta potential of NIM-SLN were used to evaluate the influence of different formulation and preparation factors. The encapsulation efficiency （EE） and drug loading of NIM-SLN were determined by RP-HPLC. The release and permeate rate of NIM from NIM-SLN were detected by modified Franz diffusion cells method. RESULTS NIM-SLN prepared by the optimal formula and technology were spherical in shape, the mean diameter of NIM-SLN was （ 104.47±3.98 ） nm, the span was （0. 96 ±0. 04）, the EE of NIM was （95.53±1.15 ） %, the drug loading was （9. 22±0. 12 ）% , and Zeta potential was - （34. 3 ± 5.1 ）mY. NIM-SLN exhibited good controlled release properties in vitro and the release rule was discvibed by Higuehi equation： O = 0. 115 6t1/2 -0. 137 3 （r2 = 0. 990 5 ）. NIM-SLN significantly enhanced the transdermal flux of NIM, compared with azone, oleic acid or clove oil alone. CONCLUSION NIM-SLN that exhibited good controlled release properties and stable percutaneous permeability in vitro were reasonable in formula, reliable in technology, and satisfied the demands of transdermal drug delivery system.