title: Ligand anchored dendrimers based nanoconstructs for effective targeting to cancer cells.
abstract: Dendrimers are considered versatile carriers especially for the treatment of diseases like cancer, AIDS, malaria etc. Cancer is a worldwide threat particularly in developing countries. A breakthrough research in this regard is a prime requirement. In the present study, folic acid was conjugated to fifth generation polypropylene imine (PPI) dendrimers and characterized through IR, NMR ((13)C and (1)H), ESI mass spectroscopy as well as electron microscopic studies. Doxorubicin (DOX), an effective anticancer drug, was used in the present study to develop and explore the anticancer potential of the dendrimer based formulations. DOX was loaded (approximately 26 and 65%) to the PPI dendrimers as well as folate conjugated PPI (PPI-FA) dendrimers, respectively. These ligand conjugated dendrimers displayed very less (approximately 3 and 4%, respectively, for PPI-FA and PPI-FA-DOX) hemolysis. The developed formulation PPI-FA-DOX was stable enough. In vitro drug release of the formulation was found to be faster in the acidic media than at the higher pH. The prepared formulation displayed a higher cell uptake in MCF-7 cancer cell lines as evidenced by fluorescence studies. The results suggested that, in future, folic acid conjugated PPI dendrimers may emerge as a better choice for anticancer drug targeting.
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar 470003 (MP), India. umeshgupta175@gmail.com
authors.forename: Umesh
authors.initials: U
authors.lastname: Gupta
authors.forename: Shailendra Kumar Dhar
authors.initials: SK
authors.lastname: Dwivedi
authors.forename: Hemant Kumar
authors.initials: HK
authors.lastname: Bid
authors.forename: Rituraj
authors.initials: R
authors.lastname: Konwar
authors.forename: N K
authors.initials: NK
authors.lastname: Jain
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000378:metabolism; D001692:Biological Transport; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D050091:Dendrimers / Q000737:chemistry* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry* / Q000378:metabolism; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005260:Female; D005492:Folic Acid / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008854:Microscopy, Electron; D049329:Nanostructures; D011126:Polypropylenes / Q000737:chemistry* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000903:Antibiotics, Antineoplastic; D050091:Dendrimers; D004337:Drug Carriers; D011126:Polypropylenes; C443641:poly(propyleneimine); D004317:Doxorubicin; D005492:Folic Acid