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S. Bhargava



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    P2.03a - Poster Session with Presenters Present (ID 464)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.03a-057 - Ligand Mediated Solid Lipid Nanoparticle of Paclitaxel for Effective Management of Bronchogenic Carcinoma (ID 3766)

      14:30 - 14:30  |  Author(s): S. Bhargava

      • Abstract

      Background:
      Lung cancer is a disease of uncontrolled cell growth in tissues of lung. It is most common cause of cancer-related deaths in men and second most common in women. It is responsible for 1.3 million deaths worldwide annually. Most common cause is long term exposure to tobacco smoke. The occurrence of lung cancer in nonsmokers, who accounts 15% cases, attributed to combination of genetic factors, radon gases, and asbestos and air pollution including second hand smoke.

      Methods:
      The treatment and management of diseases associated with lung is difficult with presently available therapeutic systems, as insufficient drug reaches to lung due to mucocilliary clearance of the medicament. The proposed drug delivery system was used to determine targeting efficiency of optimized formulation via conjugation of ligand ie Solid Lipid Nanoparticles (SLNs) bearing paclitaxel anchored with lactoferrin molecules. These systems may enhance the drug delivery to lung via receptor mediated endocytosis mechanism

      Results:
      The SLNs were prepared by modified Solvent Injection Method, and then sonicated and finally ligand anchored. The nanoparticles were characterized in-vitro for their shape and size by Scanning (SEM) & Transmission Electron Microscopic (TEM), drug entrapment, in-vitro drug release and stability. The in-vivo study comprised of biodistribution studies in various organs and fluorescence microscopy was performed. The Sulforhodamine Blue (Srb) Colorimetric Assay was performed on human lung cancer cell line (BEAS-2B) For Cytotoxicity Screening.

      Conclusion:
      The in-vitro & in-vivo studies result shows a more specific delivery of the Paclitaxel to the Lung. The cell cytotoxicity studies states that Lactoferrin coupled SLN deliver the drug more specifically and have lowtoxicity effect over the unconjugated SLN and plain drug solution.This study suggests that loading another drug will open new and exciting gateways in the management of other lung diseases. Our finding should be helpful for possible exploitation of lactoferrin as future ligand for the delivery of the drugs for treatments of other lungs diseases.

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    P3.02c - Poster Session with Presenters Present (ID 472)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.02c-002 - Mannosylated Poly (Propylene Imine) Dendrimer Mediated Lung Delivery of Anticancer Bioactive (ID 3920)

      14:30 - 14:30  |  Author(s): S. Bhargava

      • Abstract

      Background:
      Tumors originating in lung tissues or in the bronchi invade adjacent tissue and cause infiltration beyond the lung. Lung macrophages express mannose-specific endocytosis receptor that might binds or internalize mannose terminated dendrimer. Therefore, it is hypothesized that incorporation of anticancer drug into mannose anchored dendrimer will transport the drug effectively to the tumor cells via receptor mediated endocytosis. Dendrimer are easy to synthesis and better stability, Nanoscopic size range, High drug loading propensity, Dose reduction possible, Number of free surface groups available for further conjugation. The project aimed to investigate the targeting potential of mannose conjugated Poly Propyl Imine (PPI) dendrimer having potent anticancer drug, Gemcitabine in lung cancer cells. The dendrimers were conjugated so as to enhance the therapeutic potential and reduce adverse effect of anticancer drug.

      Methods:
      The 5.0 generation dendrimers were synthesized and were characterized by FTIR and Nuclear Magnetic Resonance (NMR). The PPI dendrimers prepared were then conjugated with mannose and drug was loaded. The shape and size were characterized by Transmission Electron Microscopy (TEM), drug loading efficiency, In-vitro drug release and stability studies. The ex-vivo studies constituted Hemolytic toxicity study and Cell cytotoxic study by MTT Cytotoxicity Assay on A-549 (Lung adenocarcinoma epithelial) cell line. The in-vivo studies were performed on albino rats and Pharmakokinetic parameters were studied, also Biodistribution Studies were done to access gemcitabine level attained in different organs.

      Results:
      Thus Mannosylated PPI dendrimers showed high gemcitabine loading, sustained release and excellent biocompatibility as evident by low hemolytic toxicity. MTT assay suggested high cytotoxicity of GmcH-MPPI against A549 cancer cell lines. The Presence of ligand on dendrimer molecule, elevated receptor mediated binding or internalization in AM. The developed ligand conjugated dendritic system targeted higher concentration of GmcH to lung than the free drug.

      Conclusion:
      Thus, we concluded that GmcH loaded mannosylated PPI dendritic system could have higher potential to target anticancer drug to lungs for effective chemotherapy of lung tumor.