Safwat Sally, Ishak Rania A H, Hathout Rania M, Mortada Nahed D
a Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Ain Shams University , Abbassiah , Cairo , Egypt.
Drug Dev Ind Pharm. 2017 Jul;43(7):1112-1125. doi: 10.1080/03639045.2017.1293681. Epub 2017 Mar 1.
The aim of this study is to evaluate the use of PEG/glycerides of different HLB; oleoyl macrogol-6-glycerides (Labrafil M 1944 CS) and caprylocaproylmacrogol-8-glycerides (Labrasol), compared to Labrafac lipophile as PEG-free glyceride in the preparation of nanostructured lipid carriers (NLCs). PEG/glycerides are suggested to perform a dual function; as the oily component, and as the PEG-containing substrate required for producing the PEGylated carriers without physical or chemical synthesis.
Lipid nanocarriers were loaded with simvastatin (SV) as a promising anticancer drug. An optimization study of NLC fabrication variables was first conducted. The effect of lyophilization was investigated using cryoprotectants of various types and concentrations. The prepared NLCs were characterized in terms of particle size (PS), size distribution (PDI), zeta potential (ZP), drug entrapment, in vitro drug release, morphology and drug-excipient interactions. The influence of glycerides ± PEG on the cytotoxicity of SV was evaluated on MCF-7 breast cancer cells, in addition to the cellular uptake of fluorescent blank NLCs.
The alteration between different oil types had a significant impact on PS, ZP and drug release. Both sucrose and trehalose showed the lowest increase in PS and PDI of the reconstituted lyophilized NLCs. The in vitro cytotoxicity and cellular uptake studies indicated that SV showed the highest antitumor effect on MCF-7 cancer cells when loaded into Labrasol NLCs demonstrating a high cellular uptake as well.
The study confirms the applicability of PEG/glycerides in the development of NLCs. Encapsulating SV in Labrasol-containing NLC could enhance the antitumor effect of the drug.
本研究旨在评估不同亲水亲油平衡值（HLB）的聚乙二醇/甘油酯；油酰聚乙二醇-6-甘油酯（Labrafil M 1944 CS）和辛酸癸酸聚乙二醇-8-甘油酯（Labrasol），与不含聚乙二醇的甘油酯Labrafac lipophile相比，在制备纳米结构脂质载体（NLCs）中的应用。聚乙二醇/甘油酯被认为具有双重功能；作为油性成分，以及作为生产聚乙二醇化载体所需的含聚乙二醇底物，无需物理或化学合成。
脂质纳米载体负载有辛伐他汀（SV）作为一种有前景的抗癌药物。首先对NLC制备变量进行了优化研究。使用不同类型和浓度的冷冻保护剂研究了冻干的影响。对制备的NLCs进行了粒径（PS）、粒径分布（PDI）、zeta电位（ZP）、药物包封率、体外药物释放、形态和药物-辅料相互作用等方面的表征。除了荧光空白NLCs的细胞摄取外，还评估了甘油酯±聚乙二醇对SV细胞毒性的影响。
不同油类型之间的变化对PS、ZP和药物释放有显著影响。蔗糖和海藻糖在重构冻干NLCs的PS和PDI方面增加最少。体外细胞毒性和细胞摄取研究表明，当SV负载到Labrasol NLCs中时，对MCF-7癌细胞显示出最高的抗肿瘤作用，同时也显示出高细胞摄取率。
该研究证实了聚乙二醇/甘油酯在NLCs开发中的适用性。将SV包裹在含Labrasol的NLC中可以增强药物的抗肿瘤作用。
