超临界辅助喷雾法用于固体脂质纳米粒的制备

Supercritical Assisted Atomization for Preparation of Solid Lipid Nanoparticles

关键词:  超临界辅助喷雾法  固体脂质纳米粒  固体脂质微粒  胰岛素  硬脂酸

Key words:  supercritical assisted atomization  solid lipid nanoparticles  solid lipid microparticles  insulin  stearic acid

摘要:

目的 采用超临界辅助喷雾制粒法制备固体脂质纳米粒，并考察工艺与处方因素对纳米粒理化性质的影响。方法 采用自制超临界喷雾制粒设备，制备硬脂酸脂质纳米粒，考察硬脂酸浓度、超临界流体CO₂与载体溶液流量比、喷嘴孔径等对固体脂质纳米粒粒径的影响，筛选合适的处方工艺参数；以亲水性大分子药物胰岛素为模型药物，制备载药固体脂质纳米粒，评价纳米粒的粒径、电位、包封率、释放度等理化性质。结果 制备得到的纳米粒粒径与载体浓度、超临界流体CO₂与载体溶液流量比、喷嘴孔径有关，通过处方工艺的调节，可制得平均粒径<300 nm的固体脂质纳米粒；制得的胰岛素固体脂质纳米粒的平均粒径约300 nm，包封率72.2%，载药量为3.44%，载药纳米粒在体外可实现12 h缓慢释放；处方中加入泊洛沙姆可减小纳米粒粒径和粒度分布，但药物的包封率降低，并且突释现象更明显。结论 超临界辅助喷雾制粒法可用于固体脂质纳米粒的制备，并能够对亲水性药物实现有效的包封和释放的调节。

Abstract:

OBJECTIVE To prepare the solid lipid nanoparticles(SLN) via supercritical assisted atomization(SAA) and investigate the effect of formulation and process on physicochemical characteristics of nanoparticles (NPs). METHODS With self-made SAA particle-producing equipment, stearic acid(SA) based SLN was produced, and the effect of SA concentration, flow ratio of supercritical CO₂ and material solution, pore size of nozzle, on particle size of SLN were investigated to discover the appropriate process conditions. SLN loading insulin, a hydrophilic macromolecule drug, was produced and their physicochemical characteristics was observed, such as size, zeta-potential, entrapment efficiency(EE) and drug-loading ratio(DL). RESULTS Particle size of NPs was depended on material concentration, flow ratio of supercritical CO₂ and material solution, pore size of nozzle. SLN with mean size <300 nm were obtained through formulation and process adjustment during preparation. Insulin-loaded SLN with mean size of about 300 nm, EE 72.2% and DL 3.44% was obtained, which released drug slowly during 12 h in vitro. Poloxamer-modified formulation made SLN with reduced size and distribution range, meanwhile the drug EE was decreased and burst-release was significant. CONCLUSION SAA is successfully applied to produce SLN and hydrophilic-drug-loaded SLN with modified releasing profile.