Achieving targeted intratumoural drug delivery

Understanding current drug therapies for cancer treatment

Chemotherapy: Traditional chemotherapy agents inhibit cell proliferation but can affect both cancerous and healthy cells, leading to significant side effects for patients.

Hormonal therapies: These therapies target cancers that are dependent on hormones for growth by modulating hormone production.

Immunotherapy: This enhances or utilises the body’s immune response to recognise and destroy cancer cells.

Targeted intratumoural drug delivery

Emerging therapies like immune checkpoint inhibitors and CAR-T cells are transforming oncology, but their systemic biodistribution raises safety issues, leading to suboptimal doses or even limiting their clinical development. Intratumoural drug delivery facilitated by advanced drug delivery devices or systems offers an alternative approach by concentrating drugs directly within the tumour, potentially increasing efficacy and reducing side effects by enhancing retention and reducing off-target toxicity.

However, intratumoural delivery comes with different challenges such as poor distribution within the tumour, difficulty with surgical access, reliable dosing and overcoming high tumour density and high interstitial pressure which can impede drug penetration.

Technological innovations are addressing these challenges through a variety of approaches, including optimising injection techniques, enhancing drug formulations and modifying the tumour microenvironment to improve intratumoural drug delivery for cancer treatment.

Injection techniques

Intratumoural administration can be realised through direct or image-guided injection. Modifications in needle design, such as the use of multi-hole needles and microneedles, have shown advantages, particularly in patients with firm tumours. These modifications help reduce injection pressure and distribute the drug more evenly.

Pressure-enabled drug delivery systems, such as the Pressure-Enabled Drug Delivery™ method from TriSalus Life Sciences, modulate intravascular pressure to enhance regional delivery.

Drug formulation

Suitable drug formulations, such as hydrogels, play a crucial role in improving drug loading and drug release kinetics. Shear-thinning hydrogels, which have tuneable viscosities, are particularly suited for intratumoural drug delivery. These materials can flow under shear stress, allowing for easy injection and quickly solidify upon administration, ensuring controlled release of therapeutic agents over time. Similarly, thermosensitive hydrogels, which transition from a liquid state at room temperature to a gel at body temperature, are also being explored to enhance drug retention.

These systems have shown promise in delivering a variety of therapeutic agents, including chemotherapeutics, cytokines and immunotherapy treatments.

Tumour microenvironment

The tumour microenvironment (TME) refers to the surrounding cellular and extracellular components that interact with tumour cells. These can manifest as poor blood supply and increased interstitial fluid pressure or physical barriers that obstruct drug diffusion. The composition and density of these barriers can vary widely within different tumours, affecting how well drugs are delivered. Techniques like external beam radiation and hyperthermia have been shown to reduce tumour interstitial pressure or increase tumour blood flow and vascular permeability, making the tumour more amenable to drug delivery.

Intratumoural drug delivery technology development

Given the heterogeneous nature of tumours and their microenvironments, a personalised approach to drug delivery can be considered. Understanding the biophysical properties of individual tumours, alongside robust simulation models and empirical data, could enable the development of tailored drug administration strategies.

This may involve integrating real-time feedback mechanisms that monitor drug penetration and efficacy. Additionally, techniques such as biopsies and ex vivo characterisation of the tumour microenvironment can provide insights into optimising delivery methods. A recent study has demonstrated the ability to accurately predict the spatial liposome accumulation and interstitial fluid pressure for an individual tumour based on physics-informed machine learning analysis of computed tomography (CT) imaging data.

Furthermore, Optics11Life offers nanoindenters for mechanical characterisation that can enable understanding of cancer cell mechanics such as stiffness, elasticity and hardness. These properties often differ significantly from those of healthy cells and can influence tumour behaviour, growth and response to treatment. For those developing intratumoural drug delivery devices, having this understanding is important to inform the design of delivery systems that are better adapted to the physical characteristics of the tumour, potentially improving drug penetration and therapeutic efficacy.

A significant challenge in development of intratumoural drug delivery technology is the design of needles capable of delivering viscous formulations, especially in hard-to-reach areas. This could be addressed through robotic systems. A needle designed for precise manoeuvres must be flexible enough to navigate challenging angles while being robust enough to penetrate tumour tissue without compromising the drug load.

Further preclinical research is necessary to explore factors influencing intratumoural delivery, such as flow rates, needle design, dosing and formulation characteristics. Conducting ex vivo testing or utilising intraoperative metrics can significantly aid in formulating individualised intratumoural drug delivery strategies, enhancing the overall effectiveness of cancer treatment.

The future or intratumoural drug delivery

Intratumoural drug delivery offers a promising alternative to systemic therapies by enhancing local efficacy and reducing side effects. With advances in formulation, drug delivery devices and tumour characterisation, this approach is becoming increasingly personalised and precise paving the way for more effective and safer cancer treatments.

This blog is part of a series on “The future of oncology – medical technologies that are transforming cancer treatment”. Read the blogs on innovations in surgical oncology and radiotherapy ablation technologies for cancer treatment.