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.

Hollow microneedle-mediated intradermal delivery of model vaccine antigen-loaded PLGA nanoparticles elicits protective T cell-mediated immunity to an intracellular bacterium

“…For this 0.2 × 10 6 erythrocyte-depleted splenocytes or inguinal lymph node cells were plated in complete RPMI medium in a 96 well round bottom plate for 72 h with or without 10 μg/ml OVA Endo-Fit (Worthigton) or ConA, at 37°C in a humidified incubator. After 72 h, 3 H-Thymidine (0.4 μCi/well; Amersham Biosciences Europe GmbH) was added for an additional 18 h and incorporation into DNA was measured by liquid scintillation counting (Microbeta, Perkin-Elmer Inc.).…”

“…There are other benefits in using microneedles compared to traditional hypodermic needles, like possible painless vaccination, the requirement of less trained personnel and reduced contamination risk [2]. Nowadays a wide variety of these microneedles exist, including solid, coated, dissolving and hollow microneedles [3,4].…”

“…Hollow microneedles have multiple benefits, for instance they can be used to inject a wide variety of fluids into the skin at different pressure-driven flow rates [3,5,6] and offer the highest precision in dose delivery among all microneedle types. Furthermore, they offer the possibility to screen formulations without time-consuming design and preparation of microneedles, as in case of coated and dissolving microneedles.…”

Transdermal drug delivery: 30 + years of war and still fighting!

“…The number of publications addressing these technologies, especially microneedles, is growing exponentially and recent, authorative reviews are available in the literature [19][20][21][22][23][24]. In each approach, new, aqueous pathways are created across the outer few hundred microns (give or take) of the skin allowing the barrier function of the SC to be 'short-circuited' and relaxing two key limitations of passive transdermal delivery:…”

Predicting the optimal geometry of microneedles and their array for dermal vaccination using a computational model

“…These arrays contain small projections, the microneedles, which are arranged on a back plate. Depending on the delivery approach, the microneedle can be in different forms, including hollow, coated or dissolvable microneedles (Kim et al 2012;van der Maaden et al 2012). In recent years, these microneedles have been designed with a wide variety of geometries.…”