Preparation, characterization and anti-proliferative effects of sclareol-loaded solid lipid nanoparticles on A549 human lung epithelial cancer cells

被引:58
作者
Hamishehkar, Hamed [1 ]
Bahadori, Mir Babak [2 ]
Vandghanooni, Somayeh [2 ]
Eskandani, Masoud [3 ]
Nakhlband, Ailar [2 ]
Eskandani, Morteza [2 ]
机构
[1] Tabriz Univ Med Sci, Drug Appl Res Ctr, Tabriz, Iran
[2] Tabriz Univ Med Sci, Res Ctr Pharmaceut Nanotechnol, Tabriz, Iran
[3] Univ Mohaghegh Ardabili, Fac Agr Sci, Dept Anim Sci, Ardebil, Iran
关键词
Sclareol; Labdane diterpene; Solid lipid nanoparticle (SLN); Cytotoxicity; Genotoxicity; Pharmaceutical/nutraceutical analyses; ANNEXIN-V; PHYSICOCHEMICAL CHARACTERIZATION; APOPTOSIS DETECTION; DNA FRAGMENTATION; BODY DISTRIBUTION; DRUG-DELIVERY; TUMOR-GROWTH; IN-VITRO; FORMULATION; SUPPRESSION;
D O I
10.1016/j.jddst.2018.02.017
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Here, sclareol-loaded solid lipid nanoparticles (sclareol-SLNs) was formulated and tested for potential genocytotoxicity upon A549 lung cancer cells. Sclareol-SLNs was formulated using hot homogenization. Different physicochemical features including size, zeta potential, dispersity, drug loading (DL), and encapsulation efficiency (EE) as well as in vitro drug release behavior were determined. Genotoxicity and cytotoxicity of the developed sclareol-SLNs were evaluated using DNA ladder and MTT assay, respectively. The cell death types were determined by detection of phosphatidylserine, dsDNA integrity, and proportion of different amounts in the associated cell cycle. Electron microscopy and particle size analysis showed dispersed and homogenous NPs with an average diameter of 88 nm and a high percent of EE (89%) and drug loading (42.47 mg/g). Sustained drug release was achieved at a physiologic pH, and long-term stability in terms of the size, zeta, dispersity, and EE of NPs was achieved. Cytotoxicity assay results showed that the plain sclareol inhibited A549 growth with an IC50 value of 19 mu g/mL after 24 h, yet sclareol-SLNs inhibition was perceived after 48 h. DNA fragmentation assay using gel electrophoresis showed clear fragmentation in the chromatin within the cell's treated by sclareol and NPs. Flow cytometry analyses determined early and late apoptosis in sclareol and sclareol-SLNs treated cells.
引用
收藏
页码:272 / 280
页数:9
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