紫草素纳米结构脂质载体的制备与评价
Preparation and evaluation of shikonin nanostructured lipid carriers
王昕怡 1陈佳佳 1谢祎帆 1杨帆 1尚上 1齐梦飞 1向亚津晶 1张颜 1童瑛 1沈家燕 1刘葭 1吴清1
作者信息
- 1. 北京中医药大学中药学院,北京 102488
- 折叠
摘要
目的 制备并优化紫草素纳米结构脂质载体(NLC),并对其进行表征、创面刺激性测试及抗炎活性评价.方法 通过饱和溶解度测定、脂质相容性和乳化能力筛选了紫草素NLC的处方.以粒径和多分散系数(PDI)为指标,考察紫草素NLC的制备方法,并采用该方法制备紫草素NLC,单因素法考察固液脂质比、总脂质用量、乳化剂用量和投药量的范围.通过正交试验考察固液脂质比、总脂质用量、投药量对PDI和载药量的影响,得到最优处方,并对其进行验证及表征.通过在大鼠背部表皮造成破损后连续给药,测试紫草素NLC的创面刺激性.采用脂多糖诱导RAW264.7细胞炎症模型,以NO释放率为指标评价紫草素NLC的体外抗炎活性.结果 采用Transcutol P为液体脂质,固体脂质为双硬脂酸甘油酯,乳化剂为BRIJ®O20,采用薄膜水化法制备NLC,最优处方:乳化剂用量为6％,固液脂质比为4:6,总脂质用量为6％,投药量为20mg.大鼠背部破损皮肤均未见红斑或水肿,皮肤组织结构均基本正常,同时等剂量下的紫草素NLC抑制RAW264.7释放NO的能力存在比紫草素更强的趋势.结论 制得的紫草素NLC载药量高,粒径均一.紫草素被制成NLC后,对创面无刺激性,细胞毒性有所下降,同时具有较好的抗炎活性.
Abstract
Objective To prepare and optimize the formulation of shikonin nanostructured lipid carrier(NLC)and to evaluate its characterization,wound irritation testing and anti-inflammatory activity.Methods The prescriptions of shikonin NLC were screened by saturated solubility,lipid compatibility and emulsification ability.With particle size and polymer dispersity index(PDI)as indexes,the preparation method of shikonin NLC was examined.The ranges of solid-liquid lipid ratio,total lipid dosage,emulsifier dosage and drug dosage were investigated by single factor method.Effects of solid-liquid lipid ratio,total lipid dosage and drug dosage on PDI and drug loading were determined by orthogonal experiment,and the optimal prescription was verified.The characterization of shikonin NLC was completed.The wound irritation of shikonin NLC was tested by continuous administration after damage causing to the dorsal epidermis of rats.Lipopolysaccharide induced RAW264.7 cell inflammation model was used to evaluate the in vitro anti-inflammation activity of shikonin NLCs with nitric oxide release rate as the indicator.Results Transcutol P was used as a liquid lipid,the solid lipid was glyceryl distearate,and the emulsifier was BRIJ®O20.The optimal prescription of shikonin NLC prepared by film-dispersion and hydration method was as follows:emulsifier dosage of 6％,solid-liquid lipid ratio of 4∶6,the total lipid dosage at 6％,and drug dosage at 20 mg.No erythema or edema was seen on the damaged skin on the rats'back,and the skin tissue structure was basically normal.At the same dose,shikonin NLC better inhibited the release of nitric oxide from RAW264.7 than shikonin alone.Conclusion Nanoparticles with high drug loading and uniform particle size are obtained.Shikonin NLC do not irritate the wound surface,with decreased cytotoxicity and good anti-inflammation activity.
关键词
紫草素/纳米结构脂质载体/正交试验设计/表征/刺激性评价Key words
shikonin/nanostructured lipid carrier/orthogonal test design/characterization/irritation evaluation引用本文复制引用
出版年
2024
NETL
NSTL
万方数据