Microneedles: Characteristics, Materials, Production Methods and Commercial Development

Amina Tucak, Merima Sirbubalo, Lamija Hindija, Ognjenka Rahić, Jasmina Hadžiabdić, Kenan Muhamedagić, Ahmet Čekić, Edina Vranić, Amina Tucak, Merima Sirbubalo, Lamija Hindija, Ognjenka Rahić, Jasmina Hadžiabdić, Kenan Muhamedagić, Ahmet Čekić, Edina Vranić

Abstract

Although transdermal drug delivery systems (DDS) offer numerous benefits for patients, including the avoidance of both gastric irritation and first-pass metabolism effect, as well as improved patient compliance, only a limited number of active pharmaceutical ingredients (APIs) can be delivered accordingly. Microneedles (MNs) represent one of the most promising concepts for effective transdermal drug delivery that penetrate the protective skin barrier in a minimally invasive and painless manner. The first MNs were produced in the 90s, and since then, this field has been continually evolving. Therefore, different manufacturing methods, not only for MNs but also MN molds, are introduced, which allows for the cost-effective production of MNs for drug and vaccine delivery and even diagnostic/monitoring purposes. The focus of this review is to give a brief overview of MN characteristics, material composition, as well as the production and commercial development of MN-based systems.

Keywords: coating techniques; materials; microneedle arrays; microneedles; microscale fabrication techniques; transdermal drug delivery.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 2
Figure 2
A schematic representation of drug release methods with five different types of MNs. (A) Hollow MNs pierce the skin (left) and provide the release of liquid drug formulation through the needle lumen (right). (B) Solid MNs pretreat the skin to create transient microchannels skin (left) and increase the permeability of the drug that is then, applied in the form of a transdermal patch, solution, cream, or gel (right). (C) Coated MNs with drug formulation (left) enable the fast dissolution of the coated drug in the skin (right). (D) Dissolving MNs are prepared from polymer and embedded drug in the MN matrix (left) to provide the bolus or controlled delivery of a drug (right). (E) Hydrogel MNs poke the skin, uptake interstitial fluids (right), and induce diffusion of the drug from the patch through the swollen MNs (left).
Figure 3
Figure 3
Manufacturing of MNs using photolithography [117]. (a) Deposition: As a substrate, Si wafer is exposed to steam or humidified to produce the wafer with an oxide coating. Then, the photoresistive material is spin-coated onto a substrate. (b) Patterning: Mask guided UV radiation is exposed to the photoresistive material. (c) Etching: soluble resist material is removed and SiO2 film etched. (d) Photoresist removal: in this step, the photoresist layer is removed.
Figure 1
Figure 1
Comparison of drug delivery systems (DDS) based on (1) the conventional topical formulation, (2) microneedles (MNs), and (3) hypodermal injection.
Figure 4
Figure 4
Principle of manufacturing of MNs (in-plane and out-of-plane) and MN molds by the laser cutting.
Figure 5
Figure 5
The principle of metal MN fabrication using twisted light with a spin by Omatsu et al. (Modified from [96]).
Figure 6
Figure 6
Left: MN production with micromolding (left) consisted of (a) pouring the liquid formulation, (b) vacuum degasification, (c) drying and (d) removal of MNs from the mold. Right: Atomized spraying to fill molds.
Figure 7
Figure 7
The principle of droplet-born air blowing (DAB) methods (Modified from [123]).
Figure 8
Figure 8
Fabrication of MNs by Fused deposition modelling (FDM) methods, followed by etching in alkaline solution [103,104].
Figure 9
Figure 9
Coating techniques for MNs. (a) gas-jet drying; (b) spray drying; (c) electrohydrodynamic atomization (EHDA) processes; (d) ink-jet printing.
Figure 10
Figure 10
Current MN devices. (A) Soluvia®, (B) MicronJet®600, (C) Microstructured Transdermal System®, (D) QtryptaTM, (E) SCS Microinjector®, (F) Microinfusor®, (G) MicroCor®, (H) Bullfrog® Micro-Infusion Device.

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