Intradermal drug delivery

Injection into the dermal skin layer

Vaccines can be administered via the intradermal route, i.e. injection in the dermis, one of the layers of the skin (cfr picture). This layer, underneath the epidermis, is highly vascularized and contains a large amount of immune cells, mainly dermal dendritic cells.

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.

Content

• Definition of intradermal injection
• Intradermal injection methods​
  • ​​With a normal-sized needle
  • With shorter needles
  • Without needles
• Intradermal injection used for vaccination

Intradermal injection methods

Intradermal injections can be delivered using either normal-sized needles (Mantoux technique) or devices specially designed for intradermal injection.

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 10 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 intradermal injection is intradermal microinjection. Certain micoinjection 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).

The VAX-ID® is a new device suitable for intradermal vaccination with a short needle. With this device, intradermal injections are safer and easier. The short intradermal needle, protected by a plastic holder, evokes less pain in patients and prevents needle-stick injuries. Read the VAX-ID® product specification page to learn more about the device.

Microneedle arrays for intradermal injection
Other than intradermal microinjection devices (such as VAX-ID®), which are already available 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. Only the Mantoux technique and intradermal microinjection devices, such as VAX-ID®, are already available for intradermal injections.

Tattoo devices for intradermal injection
Other than intradermal microinjection devices (such as VAX-ID®), which are already available for intradermal injection, research is currently being conducted about 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. Only the Mantoux technique and intradermal microinjection devices, such as VAX-ID®, are already available for intradermal injections.

Without needles

Intradermal liquid jet injectors
Other than intradermal microinjection devices (such as VAX-ID®), which are already available for intradermal injection, new intradermal injection devices are in development, including intradermal liquid jet injectors.

intradermal jet injectors do not contain needles. Instead, these intradermal injection tools use a high pressured, fast stream of injection liquid (or vaccine) to penetrate the skin (6). Intradermal jet injectors have been used in mass vaccination projects, or as an alternative for insulin injection for diabetic patients. However, sometimes small amounts of vaccine do not enter the skin, but “splash back” from the device, often alarming both patient and administrator (1).

Most of these intradermal needle arrays are currently only available for research. Only the Mantoux technique and intradermal microinjection devices, such as VAX-ID®, are already available for intradermal injections.

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)

Most of these intradermal needle arrays, however, are currently only available for research. Only the Mantoux technique and intradermal microinjection devices, such as VAX-ID®, are already available for intradermal injections.

Intradermal vaccination

Vaccination through intradermal injection holds many advantages compared to other types of vaccination, such as an improved immune response to vaccine, a potential reduction of the antigen dose (9), and decreased anxiety and pain (1-3;5;6). To find out more about the advantages of intradermal injection for vaccination, click here.