title: Emodin loaded solid lipid nanoparticles: preparation, characterization and antitumor activity studies.
abstract: The objective of the present study was to prepare and characterize emodin (EMO)-loaded solid lipid nanoparticles (E-SLNs) and evaluate their antitumor activity in vitro. EMO and pharmaceutical lipid material were used to prepare E-SLNs by high pressure homogenization (HPH). Poloxamer 188 and Tween 80 were used as surfactants. The physicochemical properties of the E-SLNs were investigated by particle size analysis, zeta potential measurement, drug entrapment efficiency (EE), stability and in vitro drug release behavior. The E-SLNs showed stable particle size at 28.6 ± 3.1 nm, ideal drug EE and relative long-term physical stability after being stored for 4 months. The drug release of E-SLNs could last 72 h and exhibited a sustained profile, which made it a promising vehicle for oral drug delivery. MTT assay showed that E-SLNs could significantly enhance the in vitro cytotoxicity against human breast cancer cell line MCF-7 and MDA-MB-231 cells compared to the EMO solution, while free EMO, blank SLNs (B-SLNs) and E-SLNs all showed no significant toxicity to human mammary epithelial line MCF-10A cells. Flow cytometric analysis demonstrated that E-SLNs also showed more significant cell cycle arrest effect in MCF-7 cells compared to bulk EMO solution. Hoechst 33342 staining and Annexin V-FITC/PI double staining further confirmed that E-SLNs induced higher apoptotic rates in MCF-7 cells, indicating that cell cycle arrest and apoptosis maybe the underlying mechanism of the enhanced cytotoxicity. Taken together, it seems that HPH was a simple, available and effective method for preparing high quality E-SLNs to enhance its aqueous solubility. Moreover, these results suggest that the delivery of EMO as lipid nanoparticles maybe a promising approach for cancer therapy.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Av. Padre Tomas Pereira S.J., Taipa, Macau, 999078, China.
authors.forename: Shengpeng
authors.initials: S
authors.lastname: Wang
authors.forename: Tongkai
authors.initials: T
authors.lastname: Chen
authors.forename: Ruie
authors.initials: R
authors.lastname: Chen
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Hu
authors.forename: Meiwan
authors.initials: M
authors.lastname: Chen
authors.forename: Yitao
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D004642:Emodin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D011312:Pressure; D012995:Solubility; D013194:Staining and Labeling; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008055:Lipids; D013501:Surface-Active Agents; D004642:Emodin