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Related Experiment Videos

Multistep, effective drug distribution within solid tumors.

Amotz Shemi1, Elina Zorde Khvalevsky1, Rachel Malka Gabai1

  • 1Silenseed Ltd., Jerusalem, Israel.

Oncotarget
|September 30, 2015
PubMed
Summary
This summary is machine-generated.

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Continuous intratumoral drug delivery overcomes tumor barriers. A novel model shows prolonged release enhances drug penetration and distribution, improving cancer therapy effectiveness. This approach aids drug delivery in solid tumors.

Area of Science:

  • Oncology
  • Drug Delivery
  • Biomedical Engineering

Background:

  • Solid tumors present significant challenges for drug distribution due to resistance to diffusion and poor fluid flow.
  • Current cancer therapies often struggle with efficient drug penetration within the tumor microenvironment.
  • Intratumoral drug delivery methods are limited by injection-based approaches and systemic delivery's side effects.

Purpose of the Study:

  • To model and analyze the distribution of drugs released continuously from an intratumoral source.
  • To investigate a novel drug delivery strategy that enhances penetration and efficacy in solid tumors.
  • To evaluate the potential of prolonged intratumoral drug release as an alternative to conventional methods.

Main Methods:

  • Development of a computational model simulating drug distribution from a miniature intratumoral source.
Keywords:
KRASRNAidrug deliverysolid tumortumor microenvironment

Related Experiment Videos

  • Analysis of drug transport mechanisms including diffusion, convection via interstitial fluid pressure (IFP) gradients, and mixing.
  • In vivo validation using the LODER system releasing siRNA against mutated KRAS in pancreatic cancer models.

    • Main Results:

    • The model demonstrates a multi-step drug distribution process, starting with local 'priming' and progressing to wider tumor coverage.
    • Increased tumor void volume and lymphatic perfusion facilitate drug transport away from the tumor core via hydraulic convection.
    • Sustained drug release over months leads to tumor cell death and eventual steady-state distribution throughout the entire tumor.

    Conclusions:

    • Prolonged, continuous intratumoral drug delivery is a viable strategy to overcome drug distribution barriers in solid tumors.
    • The described drug delivery mechanism, involving priming, convection, and mixing, enables comprehensive tumor treatment.
    • The LODER system's success in preclinical models and clinical trials supports the potential of this approach for pancreatic cancer therapy.