Microstructured transdermal systems for intradermal vaccine and drug delivery PART II

Types of MTS

MTS can be configured in multiple ways depending on the drug delivery objectives. Microstructures coated with vaccine formulation are a desirable configuration for vaccine applications, but there are other approaches that cover a variety of additional applications.

Advantages of solid-coated MTS for vaccine delivery

Pretreatment with MTS. In this configuration, the MTS is applied to the skin, creating temporary channels in the skin. A conventional patch or topical formulation is then applied over the pretreated area. The channels left behind in the skin provide less diffusional resistance than untreated skin, particularly for large, water-soluble drugs.

Hollow MTS. Microstructures with holes provide a means for delivery of liquid formulations. After microstructure insertion, the liquid formulation either passively diffuses through the needle holes or can be forced through the holes at a controlled rate using a micropump. This is the MTS configuration most amenable to sustained or programmable release.

Erodible MTS. The MTS array itself is made of an erodible material containing the drug. Upon insertion in the skin, the microstructures erode, releasing the drug. The delivery kinetics can be controlled by the rate of erosion.

Solid-coated MTS. In this configuration, the drug or vaccine formulation is coated on the outside of the microstructures. When the microstructures are inserted into the skin, the coated formulation releases from the microstructures and is delivered within the skin (depending on the depth of penetration).

Solid-coated MTS is a particularly advantageous configuration for vaccine delivery. Vaccine formulations coated and dried to a solid state on the microstructures offer the potential of improved vaccine stability compared with injectable formulations. By optimizing system parameters (such as needle size and shape) the vaccine coating can be delivered in very close proximity to the antigen-presenting cells within the skin — often resulting in stimulation of an immune response at much lower doses than injectable formulations. Finally, the solid-coated MTS can be administered without pain during the application and without lingering soreness, making it a very patient-friendly vaccine delivery system. The specific components and attributes of solid-coated MTS are discussed in greater detail.

The future

Aside from tuberculin tines, there are no modern MTS products on the market, but research in this area is accelerating and several products are in the development pipeline. Of these, the solid-coated MTS that are described in this article are the farthest along, but it is still likely to be a number of years before any of these receive regulatory approval and reach the market place. However, the numerous performance advantages of these systems and the ability to eliminate the needle from the vaccination process seem to ensure a healthy market for these systems.

Beyond vaccines, solid-coated MTS products may also be utilized for single dose or pulsatile delivery of other potent macromolecules and small molecules that are currently given by injection.

As the utility of the solid-coated MTS is further proven, additional MTS product configurations are likely to progress farther down the development pathway. For example, the hollow MTS with its potential to deliver liquid formulations of high molecular weight drugs in a manner similar to IV infusion without needle or catheter could have a wide ranging impact on the delivery of biopharmaceuticals. As the technology to reliably and efficiently produce the hollow microstructures reaches the same stage of robustness as the solid MTS, hollow MTS products are likely to emerge. MTS configurations that allow delivery of depot formulations are also a likely prospect for future development. Such systems would enable rapid, needle-less and pain-free application of the depot formulation, followed by removal of the MTS and sustained delivery from the depot formulation.