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Formulation and Delivery - Chemical

(T1330-01-03) Development of Hypoxia-Responsive Polymersomes for Drug Delivery to Pancreatic Ductal Adenocarcinoma (PDAC) Cells

Tuesday, October 22, 2024
1:30 PM – 2:30 PM MT

    Presenting Author(s)

  • CO

    Chukwuebuka Ozoude, MS

    Graduate Research Assistant
    North Dakota State University
    Fargo, North Dakota, United States

    • Main Author(s)

  • CO

    Chukwuebuka Ozoude, MS

    Graduate Research Assistant
    North Dakota State University
    Fargo, North Dakota, United States

    • Co-Author(s)

  • SM

    Sanku Mallik, Ph.D.

    Professor
    North Dakota State University
    Fargo, North Dakota, United States

  • CE

    Connor Edvall, BS

    Graduate Student
    North Dakota State University
    Fargo, North Dakota, United States

  • SA

    Shubhashri Ambhore, MS

    Graduate Student
    North Dakota State University
    Fargo, North Dakota, United States

Purpose: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, and new therapeutic strategies are urgently needed. Hypoxia is a significant characteristic of solid tumors. Hypoxia increases pancreatic cancer progression and metastasis by elevating the stemness markers, such as CD24 and CD44. In addition, hypoxic conditions generated by the growth of these tumors enable the cancer cells to proliferate, metastasize, and evade chemotherapy. We propose that either a CXCR4 inhibitor (AMD3100) or a STAT3 inhibitor (Narciclasine) would decrease cancer stemness and increase the effectiveness of the anticancer drug gemcitabine (GEM) in killing the hypoxic PDAC cells. Hypoxia-responsive polymersomes (HRPs) encapsulating these inhibitors are utilized to deliver synergistic combinations in PDAC tumors.

Methods: Synergy studies were conducted to determine the concentrations of the drugs that will be most effective on the PDAC cell lines. A hypoxia-responsive polymer containing polyethylene glycol-diazobenzene-polylactide was synthesized and characterized. Subsequently, drug-encapsulated, hypoxia-responsive polymersomes (HRPs) were formulated using the passive encapsulation technique. The encapsulation efficiency of the polymersome formulation was determined by HPLC.

Results: The particle sizes of encapsulated polymersomes are AMD3100 (257 ± 2 nm), GEM (227 ± 4 nm) and Narciclasine (163 ± 2 nm) were obtained. Our in vitro studies (Figure 1) demonstrated that combining AMD3100 and GEM offered a statistically significant (p < 0.05) reduction of BxPC3 spheroid volumes compared to single drug treatment.

Conclusion: The synergistic drug combinations improved anticancer activity in 2D assay and 3D cultures of PDAC cells. HRPs containing encapsulated drugs have the potential to penetrate pancreatic tumors to deliver their cargo for synergistic anticancer activity.


Effects of encapsulated drugs on BxPC3 spheroids.