A Novel Folate-Targeted Nanoliposomal System of Doxorubicin for Cancer Targeting

Targeted drug delivery systems for cancer improves anti-tumor efficacy and reduces systemic toxicity by restricting availability of cytotoxic drugs within tumors. Targeting moieties, such as natural ligands (folic acid, transferrin, and biotin) which are overexpressed on tumors, have been used to en...

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Bibliographic Details
Published in:AAPS PharmSciTech 2016-12, Vol.17 (6), p.1298-1311
Main Authors: Lohade, Atul A., Jain, Rajesh R., Iyer, Krishna, Roy, Sushant K., Shimpi, Hemant H., Pawar, Yogita, Rajan, M. G. R., Menon, Mala D.
Format: Article
Language:English
Subjects:
A549 Cells
Animals
Antineoplastic Agents - pharmacology
Biochemistry
Biomedical and Life Sciences
Biomedicine
Biotechnology
Cell Line, Tumor
Cholesterol - metabolism
Doxorubicin - pharmacology
Drug Delivery Systems - methods
Female
Folic Acid - metabolism
Humans
Ligands
Liposomes - pharmacology
Mice
Mice, Inbred C57BL
Nanoparticles - administration & dosage
Neoplasms - drug therapy
Neoplasms - metabolism
Pharmacology/Toxicology
Pharmacy
Research Article
Tissue Distribution
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Summary:Targeted drug delivery systems for cancer improves anti-tumor efficacy and reduces systemic toxicity by restricting availability of cytotoxic drugs within tumors. Targeting moieties, such as natural ligands (folic acid, transferrin, and biotin) which are overexpressed on tumors, have been used to enhance liposome-encapsulated drug accumulation within tumors and resulted in better control. In this report, we explored the scope of targeting ligand folic acid, which is incorporated in liposome systems using folic acid-modified cholesterol (CPF), enabled highly selective tumor-targeted delivery of liposome-encapsulated doxorubicin and resulted in increased cytotoxicity within tumors. Folate-tagged poloxamer-coated liposomes (FDL) were found to have significantly higher cellular uptake than conventional poloxamer-coated liposomes (DL), as confirmed by fluorometric analysis in B16F10 melanoma cells. Biodistribution study of the radiolabeled liposomal system indicated the significantly higher tumor uptake of FDL as compared to DL. Anti-tumor activity of FDL against murine B16F10 melanoma tumor-bearing mice revealed that FDL inhibited tumor growth more efficiently than the DL. Taken together, the results demonstrated the significant potential of the folate-conjugated nanoliposomal system for drug delivery to tumors.
ISSN:1530-9932
1530-9932
DOI:10.1208/s12249-015-0462-2