Mini-Review Transdermal Microneedles—A Materials Perspective R. Ali, 1 P. Mehta, 1 MS Arshad, 1 I. Kucuk, 2 M-W Chang, 3 and Z. Ahmad 1,4 Received 16 September 2019; accepted 6 November 2019 Abstract. Transdermal drug delivery is an emerging field in the pharmaceutical remit compared with conventional methods (oral and parenteral). Microneedle (MN)-based devices have gained significant interest as a strategy to overcome the skin’s formidable barrier: the stratum corneum. This approach provides a less invasive, more efficient, patient friendly method of drug delivery with the ability to incorporate various therapeutic agents including macromolecules (proteins and peptides), anti-cancer agents and other hydrophilic and hydrophobic compounds. This short review attempts to assess the various materials involved in the fabrication of MNs as well as incorporation of other excipients to improve drug delivery for novel medical devices. The focus will be on polymers, metals and other inorganic materials utilised for MN drug delivery, as well as their application, limitations and future work to be carried out. KEY WORDS: transdermal drug delivery; microneedles; materials; polymer; engineering. INTRODUCTION The route of administration is classified using the therapeutic target, drug compound and the location which is most commonly categorised into systemic or local delivery. The most common are enteral (via gastrointestinal tract) and parenteral routes. Conventional enteral methods include oral drug delivery (ODD) which has been associated with ease of administration, convenience and low costs (ease of manufac- ture) (1). However, issues remain as materials can undergo gastrointestinal degradation, poor absorption, rapid clearance and unfavourable dose-response profile, hindering the use of this route for certain active pharmaceutical ingredients or therapies (2–4). The use of injectables via the parenteral route enables direct delivery of complex drugs rapidly throughout the body. However, the psychological aspect of injecting and physical pain involved heavily reduces compli- ance as well as producing biohazardous waste and requiring a skilled administrator (5,6). There is also reduced efficiency with vaccine delivery via the parenteral route due to the muscle being targeted may be immunologically weaker with hypodermic injection than if the target was the skin (7). Transdermal drug delivery (TDD) approach provides an appealing non-invasive systemic alternative to these routes; avoiding first pass metabolism and providing drug therapy in a minimally invasive and relatively painless manner (8). This route improves bioavailability of drugs and their ability to provide systemic and local treatment. The primary barrier for drug delivery to the skin is the outermost layer, the stratum corneum (SC) which can be difficult to overcome as a result of its structure (9). It is a thin layer, 10–15 μm thick compromising of dead corneocytes. The SC forms a barrier against exogenous substances and thus therapeutically limits the type of drugs that can be delivered via this route and their efficiency (10). In order to penetrate through the intact SC, molecules need to meet a range of criteria such as good solubility, being lower than 600 Da, having a log P value between 1 and 3, possessing a high SC partition coefficient and low melting point (1). A limited number of molecules satisfy this criterion, hence there has only been 20 transdermal patches (TP) approved since 2011 in the US by the Food and Drug Administration (FDA) (7). Chemical permeation enhancers have had no significant success in improving the transdermal flux of hydrophilic and 1 The Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester, LE1 9BH, UK. 2 Institute of Nanotechnology, Gebze Technical University, 41400, Gebze, Turkey. 3 Nanotechnology and Integrated Bioengineering Centre, University of Ulster, Jordanstown Campus, Newtownabbey, Northern Ireland BT37 0QB, UK. 4 To whom correspondence should be addressed. (e–mail: zahmad@dmu.ac.uk) Abbreviations: Au, Gold; CMNs, Coated microneedles; DAB, Droplet air born; DMNs , Dissolved microneedles; EHDA, Electrohydrodynamic atomisation; FDA, Food and drug; GMNs, Glass microneedles; HA, Hyaluronic acid; HFMNs, Hydrogel forming microneedles; HMNs, Hollow microneedle; IF, Interstitial fluid; ISG, Inorganic silica glass; MSN, Mesoporous silica nanoparticles; MNS, Metal microneedles; ODD, Oral drug delivery; PCL , Polycaprolactone; Pd, Palladium; PDMS, Polydimethylsiloxane; PLA, Polylactic acid; PLGA, Poly-lactic glycolic acid; PMMA, Poly(methyl methacrylate); PS, Polystyrene; PVA, Polyvinyl alcohol; PVP , Polyvinylpyrrolidone; SC, Stratum corneum; SMNs, Solid microneedles; TDD, Transdermal drug delivery; Ti, Titanium; TP , Transdermal patches; ZMNs, Zeolite microneedles. AAPS PharmSciTech (2020) 21:12 DOI: 10.1208/s12249-019-1560-3 1530-9932/19/0000-0001/0 # 2019 American Association of Pharmaceutical Scientists