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Solid Microneedles

Transdermal delivery using solid microneedles (SMNs) is a two-step process; in the first step MN arrays are applied to the skin and then removed, this process creates microchannels; in the second step a conventional drug formulation or a transdermal drug patch is applied (Fig. 13.4A). This approach is called poke and patch [17]. SMN is technically simple to deliver and it does not require drug coating or encapsulation as with coated microneedles (CMNs) or dissolving microneedles (DMNs). Drug permeation from the formulation occurs by passive diffusion through the created microchannels. Topical semisolid dosage forms such as ointment, gel, cream, and lotions can be efficiently delivered through SMNs. This device is generally fabricated using biocompatible metals such as stainless steel and titanium, silicon, polymers, or ceramics (Fig. 13.5). SMN produces high drug permeability across the skin, with negligible tissue damage compared with conventional injections. Besides pharmaceutical or medical application, SMN is also applied for the delivery of cosmetic agents. For cosmetic application, SMN is made into stamp, pen, or roller instead of a conventional patch, for example, Derma-stamp, Dermapen, Dermaroller, and similar devices to pretreat the skin before applying collagen, serum, acne medication, or other cosmetic products [18,19]. These devices have been designed to induce skin’s natural ability to produce collagen, reduce wrinkle, treat burn scar and scars caused by sunburn, acne, and stretch mark, as well as for skin tightening [20].

For pharmaceutical applications, SMN can be used for the delivery ofvaccines, small molecules, biotherapeutic agents such as insulin, growth hormones, proteins, and peptides, as well as anticancer drugs. A study by Nalluri et al. showed that permeability of drug molecules across the skin increased with increase in the size of MN, in that they

A schematic representation of five different microneedle

Figure 13.4 A schematic representation of five different microneedle (MN) types applied to facilitate drug delivery transdermally. (A) Solid MNs for enhancing the permeability of a drug formulation by creating microholes across the skin. (B) Coated MNs for rapid dissolution of the coated drug into the skin. (C) Dissolvable MNs for rapid or controlled release of the drug incorporated within the microneedles. (D) Hollow MNs used to puncture the skin and enable release of a liquid drug through active infusion or diffusion of the formulation through the needle bores. (E) Hydrogel-forming MNs take up interstitial fluids from the tissue, thereby inducing diffusion of the drug located in a patch through the swollen microprojections [16]. (Adapted with permission from Larraneta E, et al. Microneedle arrays as transdermal and intradermal drug delivery systems: materials science, manufacture and commercial development, Mater Sci Eng R Rep 2016;104:1-32, Available from: http://dx.doi.org/10.1016/j.mser.2016. 03.001.)

used MN patch with the needle length of 0.6, 0.9, 1.2, and 1.5 mm. The permeability or diffusion coefficient values observed with these MNs were in the order of

1.5 > 1.2 > 0.9 > 0.6 mm MN > passive permeation [21]. In addition, a comparison of the effectiveness of MN array patch with that of Dermaroller MN roller suggested that array patch was superior to the rollers with similar length MN in enhancing drug permeation. The researchers attributed this effect to the higher density of MN and force of application onto the skin. SMN’s ability to enhance vaccine delivery across the skin was proved by immune response induced against diphtheria toxoid vaccine and influenza vaccine in combination with cholera toxin as an adjuvant. The result obtained was comparable with that achieved by subcutaneous injection of either vaccine [22].

Solid microneedles made of silicon, metal, and polymer

Figure 13.5 Solid microneedles made of silicon, metal, and polymer. (Images reproduced with permission from Kim YC, ParkJH, Prausnitz MR. Microneedles for drug and vaccine delivery. Adv Drug Deliv Rev 20i2;64(i4):i547—68 (Copyright 2012 Elsevier).)

Formation of microchannels in the skin layer by SMN is useful for delivery of small- as well as large-molecular-weight drugs, but is especially beneficial for the particles. A high-molecular-weight drug with poor water solubility, such as docetaxel, loaded in elastic liposomes was applied to the skin pretreated with SMNs. This strategy significantly enhanced the transdermal delivery of the drug. The lag time obtained following the application of elastic liposomes through MN-treated skin was shortened by nearly 70% relative to conventional liposomes [23]. Insulin delivery efficiency was significantly enhanced with SMN before the topical application of an insulin solution in diabetic rat, this treatment resulted in reduced blood glucose level [24].

SMNs have also been applied in combination with other permeation enhancement techniques. One such study by Chen et al. reported the use of iontophoresis to enhance the transdermal delivery ofinsulin encapsulated in nanovesicles through the holes created in skin by SMN arrays. This approach resulted in reduction of blood glucose level and the effect was comparable with that obtained after subcutaneous injection of insulin [25]. In other studies SMN was utilized in combination with iontophoresis to administer human growth hormone [26] and oligonucleotide [27], and also used in combination with sono- phoresis to deliver bovine serum albumin into the skin [28].

The main limitation of SMN is its two-step application process, which may not be very convenient for the patients. Because of this, precise dosing cannot be assured. Moreover, there is limited drug permeation enhancement through SMNs, especially for high-molecular-weight viscous liquid drug formulations. For example, when PEGylated naltrexone (polyethylene glycol-naltrexone) and propylene glycol water mixture were prepared to deliver naltrexone across the MN-treated skin, the enhanced permeation was not achieved because of the increased viscosity of the formulation [29,30]. Besides, there are other disadvantages associated with SMN. SMNs in cosmetology, such as Dermaroller and Derma-stamp, are used for multiple times and may also be shared among different individuals. This strategy may lead to skin contamination and infection. These side effects can be prevented by thoroughly cleaning the MNs after each treatment.

 
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