Intradermal delivery

Injection into the dermal skin layer | Intradermal vaccination

Dermis, an immunological active site for medicinal products

Why target skin? The skin is the body’s first line of defense, rich in immune cells and supported by a dense vascular and lymphatic network. This makes skin an optimal, yet often overlooked, site for delivery of medical products. Intradermal injection is one of the routes of administration used for vaccination. Intradermal injections can be delivered using either normal-sized needles using the Mantoux technique or specifically designed devices.

The currently used Mantoux technique requires a high amount of training. It is difficult to standardize as it uses a regular needle and syringe to be inserted at an angle of 5 to 15° bevel up. Injecting the needle too deep will lead to leakage to the subcutaneous layer (fat layer), while injecting the needle too shallow will cause leakage to the outside of the skin.

It has been shown that about 70% of intradermal injections using the Mantoux technique are incorrectly administered (Micheels & Goodman, 2018). For that reason, intradermal injection is at present not often used for vaccination, even though intradermal vaccination holds many advantages over other types of vaccination.

An alternative method for tis Mantoux technique is intradermal microinjection. Idevax is committed to developing injection devices for intradermal drug delivery. We collaborate across the healthcare and life sciences ecosystems to advance innovative delivery solutions.

As a result, our VAX-ID, an intradermal injection adapter, supports a broad range of applications across therapeutics, prevention and diagnostics.

Advancing intradermal injection with Idevax

We collaborate across the healthcare and life sciences ecosystems to advance innovative therapeutic delivery solutions and tackle key challenges in skin-based delivery of medicinal products.

Our partners include academic and industry research teams, biotechnology and pharmaceutical companies, clinical and healthcare providers, as well as public health organizations and global health agencies. Discover our partners.

If you are interested in research, clinical collaboration, commercialization, or distribution, we welcome you to get in touch and start a conversation.

Idevax, your partner in intradermal injection solutions

Our goal is to provide everyone with equal access to innovative devices for intradermal injections. In this way, we ensure that medicinal products can be administered not only more accurately but also more efficiently and patient-friendly.

To achieve this, we rely on a diverse team of experts from different parts of the world. We place a high priority on quality, fun and curiosity.

IDEVAX is an ISO13485:2016 certified company. Our VAX-ID® intradermal injection adaptors are CE marked and registered with UK MHRA. For other regions, devices are currently available for investigational use only (IUO) and research use only (RUO).

Definition of intradermal injection

Intradermal injection is one of the routes of administration used for vaccination. The three main routes are intradermal (ID) injection, subcutaneous (SC) injection and intramuscular (IM) injection. Each type targets a different skin layer:

• Subcutaneous injections are administered in the fat layer, underneath the skin.
• Intramuscular injections are delivered into the muscle.
• Intradermal injections are delivered into the dermis, or the skin layer underneath the epidermis (which is the upper skin layer). The dermis is, on most places of the human body, only a few mm thick.

Intradermal injection methods

Intradermal injections can be delivered using either normal-sized needles using the Mantoux technique or specifically designed devices.

With a normal-sized needle:

Mantoux technique for intradermal injection

The currently used Mantoux technique (see picture) requires a high amount of training. It is difficult to standardize as it uses a regular needle and syringe to be inserted at an angle of 5 to 15° bevel up. Injecting the needle too deep will lead to leakage to the subcutaneous layer (fat layer), while injecting the needle too shallow will cause leakage to the outside of the skin. It has been shown that about 70% of intradermal injections using the Mantoux technique are incorrectly administered (Micheels & Goodman, 2018). For that reason, intradermal injection is at present not often used for vaccination, even though intradermal vaccination holds many advantages over other types of vaccination. (1-5)

An alternative method for the Mantoux technique is intradermal microinjection. Certain microinjection devices, such as VAX-ID®, offer a solution to the problem of the Mantoux technique.

Using shorter needles:

Intradermal microinjection

The dermis is located right underneath the epidermis, or the upper skin layer. Therefore, it can easily be reached by a shorter needle, if that needle is placed at a 90-degree angle.

In other words, the dermis can be easily reached by intradermal microinjection. Intradermal microinjection involves injection systems especially designed for intradermal injection with mini-needles, such as the VAX-ID®. The advantage of such systems is their usability, allowing the tool to be used also by untrained staff (1;3;6). They also evoke less pain for the patient, and the shortness of the injection needle makes injections safer (1-3;5;6).

Microneedle arrays for intradermal injection

New intradermal injection devices are in development, including microneedle arrays.

Microneedle arrays consist of multiple microneedles, which can be solid or biodegradable (dissolving in the body after injection). A difference can be made between solid intradermal microneedles made from a non-degradable material, such as stainless steel, glass, or titanium; and solid microneedles with hollow centers. Sometimes intradermal microneedles are combined with an adhesive patch. (1;6)

Self-dissolving microneedles can be made of sugar, sugar derivatives, or other self-dissolving materials. The advantage of this type of intradermal vaccination is the lack of sharp waste, as the needles dissolve within minutes after vaccination. (1;6)

Most of these intradermal needle arrays, however, are currently only available for research or investigational purposes.

Tattoo devices for intradermal injection

Tattoo devices can be used for vaccination: with this technique a short injection needle (or multiple needles) penetrates the skin through vibrations at a high frequency. The main advantage of this intradermal injection method is the large surface area the vaccine is injected in, which causes it to affect a broader cell population. (1;6)

This technique, however, is currently only available for research.

Needle-free

Intradermal liquid jet injectors

Jet injectors are needle-free and use a high pressured, fast stream of injection liquid (or vaccine) to penetrate the skin (6). sometimes small amounts of vaccine do not enter the skin, but “splash back” from the device, often alarming both patient and administrator (1).

Intradermal jet injectors have been used in mass vaccination projects and in low and middle income countries, or as an alternative for insulin injection for diabetic patients.

Ballistic intradermal injectors

Other than intradermal jet injectors, ballistic injectors do not send out a liquid stream to penetrate the skin, but solid particles. Multiple versions of this intradermal injection method exist, but most of them are only available for research. Examples include the “gene gun” for transferring genes, and devices which penetrate the skin with gold or sugar particles. (1;6)

Sources:

1. Kis EE, et al. Vaccine. 2012. PMID:22100637
2. Kim YC, et al. Springer Berlin Heidelberg. 2012. PMID:21472533
3. Young F, Marra F. Vaccine. 2011. PMID:21968444
4. Combadiere B, Liard C. Human Vaccines. 2011. PMID:21817854
5. Lambert PH, Laurent PE. Vaccine. 2008. PMID:18486285
6. WHO, PATH. 2009. PDF site WHO
7. Wang PM, et al. J Invest Dermatol. 2006. PMID:16484988
8. Mitragotri S. Nat Rev Immunol. 2005. PMID:16239901
9. Zehrung D, et al. Vaccine. 2013. PMID:23176978