Department of Pharmacy

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

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    Self-assembling lisofylline-fatty acid conjugate for effective treatment of diabetes mellitus
    (Elsevier, 2019-01) Mittal, Anupama; Chitkara, Deepak
    Lisofylline is an anti-inflammatory agent with proven anti-diabetic activity. Its high solubility and rapid metabolism results in poor bioavailability and short half-life, limiting its clinical utility. We have synthesized Lisofylline-Linoleic acid (LSF-LA) conjugate which self-assembled into micelles (156.9 nm; PDI 0.187; CMC 1 μg/mL; aggregation number 54) without any surfactant and showed enhanced cellular uptake. It protected MIN6 insulinoma cells from cytokine induced cell death and enhanced insulin production under inflammatory conditions. It also suppressed the proliferation of activated peripheral blood mononuclear cells and reduced the production of inflammatory cytokines, IFN-γ and TNF-α. LSF-LA micelles exhibited reduced protein binding, significantly higher half-life (5.7-fold) and higher apparent volume of distribution (5.3-fold) than free LSF. In T1D animals, reduced blood glucose levels were observed at a reduced dose (~15 mg/kg, once daily of LSF-LA micelles vs. 25 mg/kg, twice daily of free LSF) that was further confirmed by immunohistochemical analysis.
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    Lipid based nanocarriers for effective drug delivery and treatment of diabetes associated liver fibrosis
    (Elsevier, 2021-06) Chitkara, Deepak; Mittal, Anupama
    Non-alcoholic fatty liver disease (NAFLD) is a cluster of several liver diseases like hepatic steatosis, non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver (NAFL), liver fibrosis, and cirrhosis which may eventually progress to liver carcinoma. One of the primary key factors associated with the development and pathogenesis of NAFLD is diabetes mellitus. The present review emphasizes on diabetes-associated development of liver fibrosis and its treatment using different lipid nanoparticles such as stable nucleic acid lipid nanoparticles, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, self-nanoemulsifying drug delivery systems, and conjugates including phospholipid, fatty acid and steroid-based. We have comprehensively described the various pathological and molecular events linking effects of elevated free fatty acid levels, insulin resistance, and diabetes with the pathogenesis of liver fibrosis. Various passive and active targeting strategies explored for targeting hepatic stellate cells, a key target in liver fibrosis, have also been discussed in detail in this review.