Abstract | BACKGROUND AND AIMS: METHODS:
Doxorubicin loaded apotransferrin (Apodoxonano) and lactoferrin nanoparticles (Lactodoxonano) were prepared by sol-oil chemistry. HCC in the rats was induced by 100 mg/l of diethylnitrosamine (DENA) in drinking water for 8 weeks. Rats received 5 doses of 2 mg/kg drug equivalent nanoparticles through intravenous administration. Pharmacokinetics and toxicity of nanoformulations was evaluated in healthy rats and anticancer activity was studied in DENA treated rats. The anticancer activity was evaluated through counting of the liver nodules, H & E analysis and by estimating the expression levels of angiogenic and antitumor markers. RESULTS: In rats treated with nanoformulations, the numbers of liver nodules were found to be significantly reduced. They showed highest drug accumulation in liver (22.4 and 19.5 µg/g). Both nanoformulations showed higher localization compared to doxorubicin (Doxo) when delivered in the absence of a carrier. Higher amounts of Doxo (195 µg/g) were removed through kidney, while Apodoxonano and Lactodoxonano showed only a minimal amount of removal (<40 µg/g), suggesting the extended bioavailability of Doxo when delivered through nanoformulation. Safety analysis shows minimal cardiotoxicity due to lower drug accumulation in heart in the case of nanoformulation. CONCLUSION:
Drug delivery through nanoformulations not only minimizes the cardiotoxicity of doxorubicin but also enhances the efficacy and bioavailability of the drug in a target-specific manner.
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Authors | Kishore Golla, Bhaskar Cherukuvada, Farhan Ahmed, Anand K Kondapi |
Journal | PloS one
(PLoS One)
Vol. 7
Issue 12
Pg. e51960
( 2012)
ISSN: 1932-6203 [Electronic] United States |
PMID | 23284832
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Apoproteins
- Biomarkers
- Transferrin
- Tumor Necrosis Factor-alpha
- apotransferrin
- lactoferricin B
- Doxorubicin
- Lactoferrin
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Topics |
- Administration, Intravenous
- Animals
- Antineoplastic Agents
(administration & dosage, adverse effects, pharmacokinetics)
- Apoproteins
(chemistry)
- Biomarkers
(metabolism)
- Body Weight
- Carcinoma, Hepatocellular
(drug therapy, metabolism, pathology)
- Disease Models, Animal
- Doxorubicin
(administration & dosage, adverse effects, pharmacokinetics)
- Hemolysis
(drug effects)
- Lactoferrin
(chemistry)
- Liver Neoplasms
(drug therapy, metabolism, pathology)
- Male
- Nanoparticles
(chemistry, ultrastructure)
- Rats
- Transferrin
(chemistry)
- Tumor Necrosis Factor-alpha
(blood)
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