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Author: search.filters.author.Chitkara, DeepakSubject: search.filters.subject.Docetaxel

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    Human umbilical cord blood-mesenchymal stem cell derived exosomes as an efficient nanocarrier for Docetaxel and miR-125a: Formulation optimization and anti-metastatic behaviour
    (Elsevier, 2023-06) Chitkara, Deepak; Mittal, Anupama
    Exosomes, as a nanocarrier for the co-delivery of biologicals and small anticancer molecules is yet in its infancy. Herein, we investigated hUCBMSC derived exosomes as a biogenic nanocarrier for the co-delivery of tumor suppressor miR-125a and microtubule destabilizing Docetaxel (DTX) to target the proliferative and migratory aggressiveness of the murine TNBC 4T1 cells.
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    Folate targeted hybrid lipo-polymeric nanoplexes containing docetaxel and miRNA-34a for breast cancer treatment
    (Elsevier, 2021-09) Chitkara, Deepak; Mittal, Anupama
    In spite of established evidence of the synergistic combination of hydrophobic anticancer molecule and microRNA for breast cancer treatment, their in vivo delivery has not been realized owing to their instability in the biological milieu and varied physicochemical properties. The present work reports folate targeted hybrid lipo-polymeric nanoplexes for co-delivering DTX and miR-34a. These nanoplexes exhibited a mean size of 129.3 nm with complexation efficiency at an 8:1 N/P ratio. The obtained nanoplexes demonstrated higher entrapment efficiency of DTX (94.8%) with a sustained release profile up to 85% till 48 h. Further, an improved transfection efficiency in MDA-MB-231 and 4T1 breast cancer cells was observed with uptake primarily through lipid-raft and clathrin-mediated endocytosis. Further, nanoplexes showed improved cytotoxicity (~3.5‐5 folds), apoptosis (~1.6‐2.0 folds), and change in expression of apoptotic genes (~4‐7 folds) compared to the free treatment group in breast cancer cells. In vivo systemic administration of FA-functionalized DTX and FAM-siRNA-loaded nanoplexes showed an improved area under the curve (AUC) as well as circulation half-life compared to free DTX and naked FAM-labelled siRNA. Acute toxicity studies of the cationic polymer showed no toxicity at a dose equivalent to 10 mg/kg based on the hematological, biochemical, and histopathological examination.