title: A Novel Folate-Targeted Nanoliposomal System of Doxorubicin for Cancer Targeting.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400098, Maharashtra, India.
authors.forename: Atul A
authors.initials: AA
authors.lastname: Lohade
authors.affiliation: Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400098, Maharashtra, India.
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Jain
authors.affiliation: Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400098, India.
authors.forename: Krishna
authors.initials: K
authors.lastname: Iyer
authors.affiliation: Radiation Medicine Centre, Tata Memorial Centre, Parel, Mumbai, 400012, India.
authors.forename: Sushant K
authors.initials: SK
authors.lastname: Roy
authors.affiliation: Radiation Medicine Centre, Tata Memorial Centre, Parel, Mumbai, 400012, India.
authors.forename: Hemant H
authors.initials: HH
authors.lastname: Shimpi
authors.affiliation: Radiation Medicine Centre, Tata Memorial Centre, Parel, Mumbai, 400012, India.
authors.forename: Yogita
authors.initials: Y
authors.lastname: Pawar
authors.affiliation: Radiation Medicine Centre, Tata Memorial Centre, Parel, Mumbai, 400012, India.
authors.forename: M G R
authors.initials: MG
authors.lastname: Rajan
authors.affiliation: Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400098, Maharashtra, India. maladmbcp@yahoo.co.in.
authors.forename: Mala D
authors.initials: MD
authors.lastname: Menon
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008081:Liposomes / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D008081:Liposomes; D004317:Doxorubicin; D005492:Folic Acid; D002784:Cholesterol
keywords: bioconjugation; cancer targeting; doxorubicin; folic acid; liposomes