Microneedles for drug and vaccine delivery

Abstract

Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990's when microfabrication technology enabled their manufacture as (i) solid microneedles for skin pretreatment to increase skin permeability, (ii) microneedles coated with drug that dissolves off in the skin, (iii) polymer microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications.

Conflict of interest statement

This possible conflict of interest has been disclosed and is being managed by Georgia Tech and Emory University.

Copyright © 2012 Elsevier B.V. All rights reserved.

Figures

Figure 1

Cumulative number of publications on microneedles. The number of publications was determined by searching the PubMed database (http://www.ncbi.nlm.nih.gov/pubmed/) and Web of Science (http://apps.webofknowledge.com) on 25 November 2011 using the search terms “microneedle”, “microfabricated needle”, and “nanopatch”. Conference proceedings were excluded.

Figure 2

Methods of drug delivery to the skin using microneedles (MN). Microneedles are first applied to the skin (A) and then used for drug delivery (B). Solid microneedle are used as a pretreatment, after which drug can diffuse through residual holes in skin from a topical formulation (solid MN). After insertion of drug-coated microneedles into the skin, the drug coating dissolves off the microneedles in the aqueous environment of the skin (coated MN). Drug-loaded microneedles are made of water-soluble or biodegradable materials encapsulating drug that is released in the skin upon microneedle dissolution (dissolving MN). Hollow microneedles are used to inject liquid formulations into the skin (hollow MN).

Figure 3

Solid microneedles made of silicon, metal and polymer. Images reproduced with permission from references (a) [39], (b) [343], (c) [59], (d) [344], (e) [312], (f) [53], (g) [67], (h) [52], (i) [49], (j) [71], (k) [43], and (l) [87].

Figure 4

Coated microneedles made of metal and polymer after (a,c,d,f,g,i,k) and before (b,e,h,j,l) coating.. Images reproduced with permission from references (a,b) [90], (c) [51], (d,e) [91], (f) [96], (g,f) [98], (i,j) [229], and (k,l) [99].

Figure 5

Dissolving microneedles made of water-soluble polymers and biodegradable polymers. Images reproduced with permission from references (a) [113], (b) [112], (c) [127], (d) [126], (e) [140], (f) [50], (g) [119] and (h) [130].

Figure 6

Hollow microneedles made of silicon and polymers. Images reproduced with permission from references (a) [148], (b) [149], (c) [145], (d) [150], (e) [151], (f) [156], (g) [168], (h) [345], (i) [163], (j) [317], and (k) [167].