title: Acute and subacute toxicity profiles of thymoquinone-loaded nanostructured lipid carrier in BALB/c mice.
abstract: BACKGROUND
  Thymoquinone (TQ), the predominant active lipophilic component inNigella sativaseed oil, has a variety of pharmacological properties such as anticancer activities. However, translation of TQ to clinical phase is still not possible due to its hydrophobic properties. This problem can be solved by encapsulating it in nanoformulations to enhance its pharmacological properties. In our previous study, TQ has been successfully encapsulated in a nanostructured lipid carrier (hereinafter referred to as TQNLC) with excellent physiochemical properties such as high encapsulation efficiency, high drug-loading capacity, particle diameter less than 100 nm, and stability up to 2 years. In vitro studies also proved that TQNLC exhibited antiproliferative activity toward breast and cervical cancer cell lines. However, no toxicity profile related to this formulation has been reported. In this study, we determine and compare the in vivo toxicity of both TQNLC and TQ.
  
  
  METHODS
  The in vivo toxicity (acute and subacute toxicity) study was carried out by oral administration of TQNLC and TQ to BALB/c mice. Animal survival, body weight, organ weight-to-body weight ratio, hematological profile, biochemistry profile, and histopathological changes were analyzed.
  
  
  RESULTS
  In acute toxicity, TQ that is loaded in nanostructured lipid carrier (NLC) was found to be less toxic than pure TQ. It can be concluded that encapsulation of TQ in lipid carrier minimizes the toxicity of the compound. In the subacute toxicity study, oral administration of 100 mg/kg of TQNLC and TQ did not cause mortality to either male or female but resulted in toxicity to the liver. It is postulated that long-term consumption of TQNLC and TQ may cause toxicity to the liver but not to the extent of altering the functions of the organ. For both treatments, the no observed adverse effect level (NOAEL) was found to be 10 mg/kg/d for mice in both sexes.
  
  
  CONCLUSIONS
  For long-term oral consumption, TQ and TQNLC at a dose of 10 mg/kg is safe in mice and does not exert any toxic effect. The results provide safety information of TQNLC, which would further help researchers in clinical use.
authors.affiliation: Laboratory of Molecular Biomedicine, Institute of Bioscience.
authors.forename: Yong Sze
authors.initials: YS
authors.lastname: Ong
authors.affiliation: Laboratory of Molecular Biomedicine, Institute of Bioscience; Department of Biomedical Science, Faculty of Medicine and Health Sciences.
authors.forename: Latifah
authors.initials: L
authors.lastname: Saiful Yazan
authors.affiliation: Laboratory of Molecular Biomedicine, Institute of Bioscience.
authors.forename: Wei Keat
authors.initials: WK
authors.lastname: Ng
authors.affiliation: Department of Pathology and Veterinary Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia.
authors.forename: Mustapha M
authors.initials: MM
authors.lastname: Noordin
authors.affiliation: Laboratory of Molecular Biomedicine, Institute of Bioscience.
authors.forename: Sarah
authors.initials: S
authors.lastname: Sapuan
authors.affiliation: Laboratory of Molecular Biomedicine, Institute of Bioscience.
authors.forename: Jhi Biau
authors.initials: JB
authors.lastname: Foo
authors.affiliation: Laboratory of Molecular Biomedicine, Institute of Bioscience.
authors.forename: Yin Sim
authors.initials: YS
authors.lastname: Tor
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004339:Drug Compounding; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000737:chemistry*; D031881:Nigella sativa / Q000737:chemistry; D012639:Seeds / Q000737:chemistry; D023382:Toxicity Tests, Acute
chemical_list: D016227:Benzoquinones; D008055:Lipids; C003466:thymoquinone
keywords: nanostructured lipid carrier; thymoquinone; toxicity