Microneedle System for Transdermal Drug and Vaccine Delivery: Devices, Safety, and Prospects

Abstract

Microneedle (MN) delivery system has been greatly developed to deliver drugs into the skin painlessly, noninvasively, and safety. In the past several decades, various types of MNs have been developed by the newer producing techniques. Briefly, as for the morphologically, MNs can be classified into solid, coated, dissolved, and hollow MN, based on the transdermal drug delivery methods of "poke and patch," "coat and poke," "poke and release," and "poke and flow," respectively. Microneedles also have other characteristics based on the materials and structures. In addition, various manufacturing techniques have been well-developed based on the materials. In this review, the materials, structures, morphologies, and fabricating methods of MNs are summarized. A separate part of the review is used to illustrate the application of MNs to deliver vaccine, insulin, lidocaine, aspirin, and other drugs. Finally, the review ends up with a perspective on the challenges in research and development of MNs, envisioning the future development of MNs as the next generation of drug delivery system.

Keywords: drug delivery methods; fabricating methods; materials; microneedle; structures; transdermal drug delivery.

Figure 1.

Diagrams showing various microneedle drug delivery approaches. (A) Solid microneedles, for skin pretreatment to create microchannels, followed by the application of transdermal patch; (B) coated microneedles, for deposition of drug formulations into the skin, followed by removal of microneedles; (C) dissolving microneedles, incorporated into the substrate of microneedles, remaining in the skin and dissolving over time to release the drugs; and (D) hollow microneedles, for inserted into the skin and continuous infusion of drug through the created microchannels.

Figure 2.

Illustration of coating approaches used to coat microneedles: (A) dip-coating, (B) gas-jet drying, (C) spray coating, and (D) electrohydrodynamic atomization–based process, and (E) ink-jet printing. (Images reprinted with permission from Haj-Ahmad et al.)

Figure 3.

(A) Out-of-plane and (B) in-plane microneedles.

Figure 4.

Micromolding process to fabricate BCMN-G. BCMN-G indicates bioceramic microneedle with gelatin substrate. (Images reprinted with permission from Cai et al.)

Figure 5.

(A) Description of functional polyplexes released from MNs coated with pH-responsive PMA after applied on the skin. (B) Illustration of delivery of polyplexes with surface mannose moieties to intradermal resident APCs after releasing from MNs. APC indicates antigen-presenting cells; MNs microneedles; PMA, polyelectrolyte multilayer assembly. (Images reprinted with permission from Kim et al.)

Figure 6.

The schematic illustration of the microneedles used for delivery of insulin. (Images reprinted with permission from Ling and Chen.)