Department of Pharmacy

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Author: search.filters.author.Mittal, AnupamaSubject: search.filters.subject.Breast cancer

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    Belinostat loaded lipid–polymer hybrid nanoparticulate delivery system for breast cancer: improved pharmacokinetics and biodistribution in a tumor model
    (RSC, 2023-10) Chitkara, Deepak; Mittal, Anupama
    Despite various treatment modalities for breast cancer, it still persists as one of the most diagnosed types of cancer in females. The recent investigations in the epigenetics of breast cancer reveal several aberrations in the expression levels of various HDAC enzymes. Henceforth, the present work entails the formulation and characterization of a lipid polymer-based hybrid nanoparticulate (LPN) system for delivery of an epigenetic modulator drug, Belinostat, for its clinical application in breast cancer. The size of Belinostat nanoparticles prepared using a modified hot homogenization method was found to be 166.6 ± 19.95 nm with an encapsulation efficiency of 94.5 ± 5.1%. In vitro characterization for cytotoxicity, cellular uptake, and protein expression in two different breast cancer cells, 4T1 and MCF 7, revealed the superiority of the formulation in comparison with the free drug in MCF 7 cells. Subsequently, the behaviour of the formulation in in vivo settings of healthy and breast cancer xenograft bearing animals was analyzed using pharmacokinetic and biodistribution studies. The results revealed that the formulation demonstrated multi-fold improvement in the pharmacokinetic parameters in tumor bearing animals when compared with the free drug while no difference in pharmacokinetic behaviour was observed in healthy animals indicating the altered biodistribution and specificity of the formulation in breast tumor. This was confirmed by the biodistribution studies exhibiting 20-fold improved uptake and retention of the nanoparticulate formulation in tumor tissues of the animal model at the end of 4 h. Thus, the developed LPN system holds potential to act as a novel drug delivery system for Belinostat with several advantages over the free drug.
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    Docetaxel and alpha-lipoic acid co-loaded nanoparticles for cancer therapy
    (Future Science Group, 2019-04) Chitkara, Deepak; Mittal, Anupama
    The current study aims to co-deliver docetaxel (DTX) and alpha-lipoic acid (ALA) using solid lipid nanoparticles (SLNs) as a carrier for the treatment of breast cancer. Methods: Computational analysis was used to screen different solid lipids as carriers, following which SLNs were prepared and characterized. Furthermore, antioxidant activity assays and cell culture studies were performed. Results:In vitro assessment in 4T1 (murine mammary carcinoma) and MCF-7 (human breast adenocarcinoma) cells revealed enhanced efficacy of the co-loaded SLNs as compared with free drugs and single drug-loaded SLNs. Increased apoptosis following treatment with DTX-ALA co-loaded SLN was also observed
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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.