title: A target-specific oral formulation of Doxorubicin-protein nanoparticles: efficacy and safety in hepatocellular cancer.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) also known as malignant hepatoma is a most common liver cancer. Doxorubicin (Doxo) is an anti-cancer drug having activity against a wide spectrum of cancer types. Clinical Utility of doxo has been limited due to its poor bioavailability and toxicity to heart and spleen. Furthermore, cancer chemotherapeutics have limited oral absorption. Transferrin family proteins are highly abundant and plays important role in transport and storage of iron in cells and tissues. Since apotransferrin and lactoferrin receptors are highly expressed on the surface of metabolically active cancer cells, the principal objective of present study is to evaluate efficacy of doxorubicin loaded apotransferrin and lactoferrin nanoparticles (apodoxonano or lactodoxonano) in oral treatment of HCC in rats.
  
  
  METHODS
  HCC was induced in rats by supplementing 100 mg/L of diethylnitrosamine (DENA) in drinking water for 8 weeks. A week after the last day of DENA administration, rats were divided into four groups, each group comprising of five animals. Each group was administered with one of the drug viz., saline, doxorubicin (doxo), apodoxonano and lactodoxonano (4 mg/ kg equivalent of drug). In each case, they received 8 doses of the drug orally with six day interval. One week after the last dose, anticancer activity was evaluated by counting the liver nodules, H & E analysis of tissue sections and expression levels of angiogenic and antitumor markers.
  
  
  RESULTS
  In rats treated with apodoxonano and lactodoxonano, the number of neoplastic nodules was significantly lower than that of rats administered with saline or with doxo. Apodoxonano and lactodoxonano did not exhibit decrease in mean body weight, which was markedly reduced by 22% in the case of doxo administered rats. In rats treated with nanoformulations, the number of liver nodules was found reduced by >93%. Both nanoformulations showed significantly high localization in liver compared to doxo.
  
  
  CONCLUSIONS
  Apodoxonano and lactodoxonano showed improved efficacy, bioavailability and safety compared to doxo for treatment of HCC in rats when administered orally.
authors.affiliation: 2. Department of Biochemistry, University of Hyderabad, and Hyderabad 500046 India; ; 3. Centre for Nanotechnology, University of Hyderabad, and Hyderabad 500046 India.
authors.forename: Kishore
authors.initials: K
authors.lastname: Golla
authors.forename: Cherukuvada
authors.initials: C
authors.lastname: Bhaskar
authors.forename: Farhan
authors.initials: F
authors.lastname: Ahmed
authors.forename: Anand K
authors.initials: AK
authors.lastname: Kondapi
keywords: Hepatocellular carcinoma; Oral chemotherapy; apotransferrin nanoparticles; doxo; lactoferrin nanoparticles.