Author of

• 18502

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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
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18504

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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): M. 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.