title: Transferrin receptor targeted PLA-TPGS micelles improved efficacy and safety in docetaxel delivery.
abstract: The aim of this work was to develop targeted polymeric micelles of poly-lactic acid-D-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS), which are assembled along with D-alpha-tocopheryl polyethylene glycol 1000 succinate-transferrin conjugate (TPGS-Tf), and loaded docetaxel (DTX) as a model drug for enhanced treatment of lung cancer in comparison to non-targeted polymeric micelles and DTX injection (Docel™). A549 human lung cancer cells were employed as an in vitro model to access cytotoxicity study of the DTX loaded polymeric micelles. The safety of DTX formulations were studied by the measurement of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and total protein levels in bronchoalveolar lavage (BAL) fluid of rats after the treatments. The IC50 values demonstrated that the non-targeted and transferrin receptor targeted polymeric micelles could be 7 and 70 folds more effective than Docel™ after 24 h treatment with the A549 cells. Results suggested that transferrin receptor targeted polymeric micelles have showed better efficacy and safety than the non-targeted polymeric micelles and Docel™.
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, U.P., India.
authors.forename: Rahul Pratap
authors.initials: RP
authors.lastname: Singh
authors.affiliation: Department of Zoology, Faculty of Science, Banaras Hindu University, Varanasi 221005, U.P., India.
authors.forename: Gunjan
authors.initials: G
authors.lastname: Sharma
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, U.P., India.
authors.lastname: Sonali
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, U.P., India.
authors.forename: Poornima
authors.initials: P
authors.lastname: Agrawal
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, U.P., India.
authors.forename: Bajarangprasad L
authors.initials: BL
authors.lastname: Pandey
authors.affiliation: Department of Zoology, Faculty of Science, Banaras Hindu University, Varanasi 221005, U.P., India.
authors.forename: Biplob
authors.initials: B
authors.lastname: Koch
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, U.P., India; Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi 221005, India. Electronic address: muthubits@rediffmail.com.
authors.forename: Madaswamy S
authors.initials: MS
authors.lastname: Muthu
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D065546:Drug Liberation; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008823:Micelles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D011990:Receptors, Transferrin / Q000378:metabolism*; D012449:Safety; D013386:Succinates / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D043823:Taxoids / Q000737:chemistry* / Q000494:pharmacology; D014168:Transferrin / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011990:Receptors, Transferrin; D013386:Succinates; D043823:Taxoids; D014168:Transferrin; C514223:poly(lactide)-tocopheryl polyethylene glycol succinate; D000077143:Docetaxel; D011092:Polyethylene Glycols; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase
keywords: Cytotoxicity; Lung cancer; Nanomedicine; Nanotechnology; Polymeric micelles; Safety; Transferrin conjugation