title: Nanoemulsion loaded with lycobetaine-oleic acid ionic complex: physicochemical characteristics, in vitro, in vivo evaluation, and antitumor activity.
abstract: BACKGROUND
  Intravenous injection of lycobetaine was found to show significant cytotoxic activity against (inter alia) Lewis lung carcinoma, but its therapeutic use is largely limited due to an extremely short half-life in blood. This study aimed at developing a novel lipid nanocarrier-based formulation for lycobetaine delivery. The formulation is feasible for scale-up production, exhibiting good parenteral acceptability and improved circulation characteristics.
  
  
  METHODS
  To enhance its lipophilicity, oleic acid was selected to form ionic complexes with lycobetaine (LBT). The nanoemulsion loaded with LBT-oleic acid complex (LBT-OA-nanoemulsion) and PEGylated LBT-OA-nanoemulsion (NE) (LBT-OA-PEG-NE) were prepared by a simple high-pressure homogenization method.
  
  
  RESULTS
  A high-encapsulation efficiency of around 97.32% ± 2.09% was obtained for LBT-OA-PEG-NE under optimized conditions. Furthermore, the in vivo pharmacokinetics and biodistribution of LBT-OA-NE, LBT-OA-PEG-NE, and free LBT were studied in rats. Free LBT and LBT-OA-PEG-NE displayed AUC0-10h (area under the concentration-time curve from 0 to 10 hours) of 112.99 mg/L*minute and 3452.09 mg/L*minute via intravenous administration (P < 0.005), respectively. Moreover, LBT-OA-PEG-NE showed significantly lower LBT concentration in the heart, liver, and kidney, while achieving higher concentration of LBT in the lung when compared to free LBT at the same time (P < 0.005). The LBT-OA-PEG-NE exhibited higher growth inhibitory effect and longer survival time than free LBT in both heterotopic and lung metastatic tumor models.
  
  
  CONCLUSIONS
  These results demonstrated that LBT-OA-PEG-NE is an attractive parenteral formulation for cancer therapy.
authors.affiliation: Key Laboratory of Drug Targeting, Ministry of Education, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Hua
authors.initials: H
authors.lastname: Lu
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D047151:Amaryllidaceae Alkaloids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004655:Emulsions / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D007212:Indolizines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D000442:Octanols; D019301:Oleic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D016019:Survival Analysis; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D047151:Amaryllidaceae Alkaloids; D000970:Antineoplastic Agents; D004655:Emulsions; D007212:Indolizines; D000442:Octanols; C016175:ungeremine; D019301:Oleic Acid
keywords: antitumor activity; in vivo studies; lycobetaine; nanoemulsion; oleic acid; polyethylene glycol