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采用正丁醇作为辅助表面活性剂,根据 o/w 微乳液猝灭技术制备固体脂质纳米粒的新方法。

A novel method to produce solid lipid nanoparticles using n-butanol as an additional co-surfactant according to the o/w microemulsion quenching technique.

机构信息

Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Chem Phys Lipids. 2013 Sep;174:32-8. doi: 10.1016/j.chemphyslip.2013.05.001. Epub 2013 Jun 3.


DOI:10.1016/j.chemphyslip.2013.05.001
PMID:23743405
Abstract

Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are novel medicinal carriers for controlled drug release and drug targeting in different roots of administration such as parenteral, oral, ophthalmic and topical. These carriers have some benefits such as increased drug stability, high drug payload, the incorporation of lipophilic and hydrophilic drugs, and no biotoxicity. Therefore, due to the cost-efficient, proportionally increasable, and reproducible preparation of SLN/NLC and the avoidance of organic solvents used, the warm microemulsion quenching method was selected from among several preparation methods for development in this research. To prepare the warm O/W microemulsion, lipids (distearin, stearic acid, beeswax, triolein alone or in combination with others) were melted at a temperature of 65°C. After that, different ratios of Tween60 (10-22.5%) and glyceryl monostearate (surfactant and co-surfactant) and water were added, and the combination was stirred. Then, 1-butanol (co-surfactant) was added dropwise until a clear microemulsion was formed and titration continued to achieve cloudiness (to obtain the microemulsion zone). The warm o/w microemulsions were added dropwise into 4°C water (1:5 volume ratio) while being stirred at 400 or 600 rpm. Lipid nanosuspensions were created upon the addition of the warm o/w microemulsion to the cold water. The SLN were obtained over a range of concentrations of co-surfactants and lipids and observed for microemulsion stability (clearness). For selected preparations, characterization involved also determination of mean particle size, polydispersity and shape. According to the aim of this study, the optimum formulations requiring the minimum amounts of 1-butanol (1.2%) and lower temperatures for creation were selected. Mono-disperse lipid nanoparticles were prepared in the size range 77 ± 1 nm to 124 ± 21 nm according to a laser diffraction particle size analyzer and transmission electron microscopy. This method for preparing lipid nanoparticles by warm o/w microemulsion quenching was found to be more cost efficient and proportionally increasable in comparison with other preparation methods such as high pressure homogenization. These lipid nanoparticles, due to the combination of hard lipids with soft and/or liquid lipids, become good candidates for a wide range of medicaments as carriers for pharmaceutical and medicinal purposes.

摘要

固体脂质纳米粒(SLN)和纳米结构化脂质载体(NLC)是新型药物载体,可用于控制不同给药途径(如肠胃外、口服、眼用和局部用)的药物释放和药物靶向。这些载体具有一些优点,如增加药物稳定性、高载药量、亲脂性和亲水性药物的包封、无生物毒性等。因此,由于 SLN/NLC 的制备成本低、可按比例增加且可重复制备,并且避免了使用有机溶剂,因此选择从几种制备方法中选择温微乳液淬火法来进行本研究的开发。为了制备温 O/W 微乳液,将脂质(硬脂酸双十八烷基酯、硬脂酸、蜂蜡、三油酸甘油酯单独或组合使用)在 65°C 的温度下熔化。之后,加入不同比例的 Tween60(10-22.5%)和甘油单硬脂酸酯(表面活性剂和助表面活性剂)和水,并搅拌。然后,将 1-丁醇(助表面活性剂)逐滴加入,直到形成澄清的微乳液并继续滴定直至出现混浊(以获得微乳液区)。在 400 或 600 rpm 搅拌下,将温 o/w 微乳液逐滴加入 4°C 的水中(体积比为 1:5)。当将温 o/w 微乳液加入冷水中时,会形成脂质纳米混悬液。在助表面活性剂和脂质的浓度范围内,得到 SLN,并观察微乳液的稳定性(澄清度)。对于选定的制剂,特征描述还包括测定平均粒径、多分散性和形状。根据本研究的目的,选择需要最低 1-丁醇(1.2%)用量和更低温度来制备的最佳配方。根据激光衍射粒度分析仪和透射电子显微镜,制备出粒径在 77 ± 1nm 至 124 ± 21nm 范围内的单分散脂质纳米粒。与高压匀质等其他制备方法相比,通过温 o/w 微乳液淬火法制备脂质纳米粒的方法更具成本效益且可按比例增加。这些由于硬脂质与软质和/或液态脂质结合而具有良好性质的脂质纳米粒,成为了广泛药物作为药物载体的候选物。

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