Drug delivery for advanced therapies – from targeting tumours to crossing the blood-brain barrier

Advanced therapies hold remarkable potential for indications from oncology to regenerative medicine.

Yet, with a diversity of modalities - including both CAR-T cell therapies and nucleic acid - their successful delivery often poses challenges - whether it’s ensuring precision targeting, mitigating immune response, or addressing cost and usability constraints.

So how can we advance the delivery of these complex therapies?

TTP’s Stuart Lowe, Head of Advanced Therapies, and Matt Parker, Device Innovation Lead recently sat down to share expert insights into overcoming drug delivery challenges and key device considerations for advanced therapies. #

We've highlighted some of the topics discussed, but watch the full video below to view all of the team's insights.

Encapsulation: advancing targeted delivery

Emerging delivery strategies, such as encapsulation, are playing a vital role in improving the effectiveness of therapies. In regenerative medicine, therapeutic cells can be embedded in hydrogel capsules or implantable devices to localise delivery or prevent attack by the immune system. Encapsulation can also be an effective strategy in the manufacture of cell therapies, as it can protect developing cells from shear in large-scale manufacture.

In nucleic acid therapies, direct RNA injection leads to rapid degradation, making encapsulation in protective carriers like synthetic lipid nanoparticles essential.. Advancements such as adding surface antibodies to nanoparticles enable targeted delivery to specific tissues or cancer cells - beyond passive liver accumulation, significantly enhancing treatment efficacy.

Addressing challenges in solid tumour treatments

While CART-cell therapies have enjoyed success in targeting haematological cancers, treating solid tumours presents greater delivery challenges.

The therapy may not effectively reach the tumour site because of immune evasion and barriers to infiltration, requiring additional strategies. These include preconditioning tumours to become more receptive ("hot"), using checkpoint inhibitors, and optimising cell trafficking and targeting to improve therapeutic performance.

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Localised delivery for complex conditions

Immune-privileged sites like the brain present a biological barrier to the delivery of advanced therapies – often meaning that the required therapeutic dose is unnecessarily high, adding cost and risk of side effects. In the gene therapy space, novel formulations are addressing the blood-brain barrier, opening new possibilities for treating neurological conditions that were previously inaccessible to advanced therapies.

Case study: Treefrog Therapeutics and regenerative medicine

Treefrog Therapeutics exemplifies innovation in advanced therapy delivery. They use alginate hydrogel encapsulation to create a 3D biomimetic niche for stem cell growth, enabling them to differentiate into neural cells for treating neurological conditions. The encapsulation also shields cells from mechanical stress during transplantation, significantly increasing cell viability. Improper injection of these encapsulated cells into the brain can lead to uneven distribution, forming dense cell depots with poor tissue coverage. However, TreeFrog is optimising delivery methods by refining injection techniques and hydrogel formulations to ensure controlled degradation, homogeneous cell distribution, and sustained release at the target site. This approach aims to improve integration with host tissue, enhance cell survival rates, and ultimately lead to improved therapeutic outcomes.

The future of targeted and localised therapies

The shift toward targeted and localised delivery is particularly important for gene therapies aimed at specific tissues, such as the eye or brain. Combining mechanical delivery solutions with biological approaches has proven more effective than relying solely on biology or chemistry. This multidisciplinary integration is unlocking new possibilities for advanced therapies, paving the way for more precise and effective treatments.

To watch their full conversation, watch the video on cracking the code of drug delivery for advanced therapies.

About TTP's Drug Delivery consulting team

From blank sheet to clinical reality, TTP's Drug Delivery Design and Development team creates ground-breaking solutions to solve the toughest drug delivery challenges. With deep engineering, human factors, and scientific expertise, we guide you through every stage of drug delivery device development - from early exploration to manufacturing and final launch. Backed by an extensive track record we expertly navigate constraints to develop robust, efficient, scalable devices - enabling the delivery of transformative therapies and enhanced patient experiences.

Find out how we can help you with your drug delivery consulting needs.

TTP's Drug Delivery team is part of our broader Medical Device Consulting team, consisting of 300+ engineers, scientists, and human factors specialists. For nearly four decades we've partnered with clients to develop impactful solutions, helping them achieve commercial success. See our approach to medical device design and development.

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More insights on drug delivery for advanced therapies

 Read all insights into solving the complexities of formulation, containment and delivery in next generation therapies.

Read more

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