How to design catheters for targeted drug delivery

At its core, developing catheters for targeted drug delivery relies on combining the appropriate tubing with a tip for delivering the therapy at the distal end, as well as a connection for introducing the drug at the proximal end. Effective implementation of this requires us to consider several design details, including:

• The flexibility and axial stiffness of the tube.
• Material selection based on drug exposure and internal use in humans.
• Joining methods between changes in tube diameter and fixing hubs, tips, needles, and other related components.
• Design of handles (mouldings) for the proximal ends to allow users to successfully position the catheter during treatment.

Flexibility and axial stiffness of the tube

This is a vital but tricky area where compromise is key.

Clearly if we are working in an area where the access has a small diameter and is a long distance from the entry point, we need a long thin, flexible tube that would enable us to go around a tortuous path as well. However, especially with drug delivery, we may well need to exert some force with the tip once we arrive; for example, to pierce a membrane with a needle. We will therefore need good axial stiffness. However, stiffness and flexibility are potentially competing attributes.

To achieve these two desired attributes in tandem, there are things we can do:

• Wire braiding in the plastic lumens is an option where thin stainless steel wires can be re-flowed into Pebax tubing. The braiding is “knitted” on a specialist machine and aspects can be varied along the length, such as pattern and pattern pitch.
• A metal inner lumen can be added within the body of the catheter either in sensitive areas along the length of the tube or along the entire length. The needle can be fixed to the end of the inner support and be made to retract or extend as required. These metal lumens are typically stainless steel, thin-walled tubes with laser cuts to aid flexibility while retaining axial strength for puncturing and reducing dither. This is the difference in movement in the tip in comparison to the input movement by the user.
• There is also the possibility of a Nitinol tube. Nitinol is a hyper-flexible material which can offer some benefits, but is both costly and difficult to join.

Material selection

When choosing a material for the catheter, there are dozens of design considerations that need to be addressed. These include the type and viscosity of drug being delivered, what sort of manoeuvrability the tubing will need to navigate internal organs, or the level of drug exposure required at the target site. Other factors also need to be considered, such as any ballooning or manipulation required of the catheter itself as part of the therapy delivery.

Engineering analysis

Before committing to physical prototypes, engineering analysis is an effective way to save both time and investment by simulating different drug delivery scenarios within your design constraints. For example, flow is often a key aspect of catheter-based drug delivery. This often involves an inlet and outlet catheter, which is designed to isolate an area around the key organ and allow perfusion through it. To ensure the patient’s well-being, there is often a minimum flow rate required. Several other constraints also impact this flow, such as the maximum diameter a catheter can be to navigate veins or arteries.This also means understanding the characteristics of the drug or fluid early in development, as some chemotherapy formulations can exhibit complex, non-Newtonian rheology. If these behaviours are not properly characterised, they can introduce additional challenges and may lead to costly changes to design inputs or performance requirements later in development.

Flow analysis and models are an effective way to corroborate proposed designs against expected outcomes and calculations. By testing through simulation, you can rapidly progress to early-stage ‘full’ catheter prototypes for testing on-site with clients.

Catheter prototyping

A common first step in catheter development for targeted drug delivery is to test the proposed approach using on-market products. This allows teams to quickly identify design limitations and additional, bespoke requirements for the given therapy. Once these requirements have been captured, the next stage is to rapidly produce early prototypes of a bespoke catheter design for testing and even potential early in vivo trials. There are several catheter design aspects that need to be considered at this stage, including plastic lumens and hypotubes, reinforcing braids, balloons, radiopaque markers, and coatings.

Developing prototypes early is an essential step in helping to de-risk development further down the line. This ultimately accelerates the path to a viable, clinically effective solution tailored to a therapy’s specific delivery challenges.

Device testing for catheter development

As with all medical device development, testing is required to determine if the proposed design meets its intended requirements. For catheters, this involves carrying out several key tests, among others:

• Tortuous path tests – can we navigate the tip to the target site?

The aim of tortuous path tests is to determine whether the tip of the catheter can navigate to the site of interest.

These tests might involve building a specific fixture to emulate the envisaged path, where 3D printing comes into its own, and passing the development catheter along the path.

We will typically monitor friction against insertion forces and, if there is a needle, the accuracy with which it can hit a target once it emerges from the catheter tip.

• Flow testing – can we achieve the predicted flows?

To test for predicted flows, we will generally carry out extensive fluid modelling, then compare the calculations to real results, by simply passing a relevant liquid down the tube at a known driving pressure.

• Pressure testing – can we contain the pressures commensurate with the flow?

As discussed earlier, the final catheter may have joins along the length. If we expect to deliver liquid (drug) along the catheter, we must test that the tubes do not leak. This is normally done as a pressure decay test at the highest expected in-use pressure, plus a safety factor which can be anywhere from 1.5 times in-use upwards. It is important to set a relevant and meaningful safety factor as the tubes are generally very small and thin, meaning a safety factor of 5 is often unobtainable.

• Leak testing – can we fully contain the fluid while navigating a tortuous path?

While carrying out pressure testing, we will be looking for leaks.

If we are delivering a strong drug (e.g. a chemotherapy) we must ensure we won’t deliver it to anywhere except the site of interest.

User-centred catheter design

Catheters are used by professionals, so design for use is centred around understanding the context of use and the requirements of the clinicians who will interact with the device. Key Opinion Leaders (KOLs) play an important role in this process, helping to identify user needs, procedural constraints and preferences. The key is to balance these insights with the technical development of the device, ensuring the final design meets clinical needs without losing sight of performance, manufacturability or development constraints.

Generally, catheter design is based on making the device as simple to use as possible, as once in use the user has little time to focus on anything but the procedure.

High on the list of key design features are:

• Size – The catheter must be small enough to allow access to the area of interest.
• Robustness – The device must stand up to any foreseeable challenges, including potential additional force and flexibility required to navigate it into position.
• User expectations – The use model must fit in with user expectations and the realities of clinical workflow – the less complicated the better. This often leads us to design the device to be as close to current on-market products as possible, while striving to add improvements where we can.

Manufacturing catheters at scale

It is important to start conversations with the proposed manufacturer early in development. Not only does this help to prepare the design for manufacture, but it also supports a smoother transition to manufacturing once the design is finalised. It also brings in specialist input across areas such as tooling, moulding, assembly, final test, packaging and sterilisation, all of which can influence design decisions.

Ensuring that manufacturing considerations are reflected in the design from an early stage helps reduce risk as projects progress. This is particularly important as development moves towards production engineering, design verification and validation, and ultimately regulatory submission. Our experience across catheter and other invasive device programmes shows that addressing these factors early can help avoid rework and create a clearer path to manufacture.

Conclusion

Targeted drug delivery continues to drive new requirements for catheter design, as therapies become more precise and treatment pathways move closer to the patient. This creates growing pressure on devices to deliver consistent performance in complex environments, while remaining simple to use. Compounding this with changes in drug formulation, route of administration and care settings, introduces further design constraints that need to be addressed early in development.

Balancing mechanical performance, usability and manufacturability from the outset is the best way to ensure a smoother route to success in catheter design. By combining detailed engineering with a clear understanding of clinical use, it is possible to develop catheter solutions that meet both technical and practical demands.