Europe PMC Funders Author ManuscriptsPurpose-Design and evaluation of a novel laser-based method for micromoulding of microneedle arrays from polymeric materials under ambient conditions. The aim of this study was to optimise polymeric composition and assess the performance of microneedle devices that possess different geometries.Methods-A range of microneedle geometries was engineered into silicone micromoulds, and their physicochemical features were subsequently characterised.Results-Microneedles micromoulded from 20% w/w aqueous blends of the mucoadhesive copolymer Gantrez® AN-139 were surprisingly found to possess superior physical strength than those produced from commonly used pharma polymers. Gantrez® AN-139 microneedles, 600 μm and 900 μm in height, penetrated neonatal porcine skin with low application forces (>0.03 N per microneedle). When theophylline was loaded into 600 μm microneedles, 83% of the incorporated drug was delivered across neonatal porcine skin over 24 h. Optical coherence tomography (OCT) showed that drug-free 600 μm Gantrez® AN-139 microneedles punctured the stratum corneum barrier of human skin in vivo and extended approximately 460 μm into the skin. However, the entirety of the microneedle lengths was not inserted.Conclusion-In this study, we have shown that a novel laser engineering method can be used in micromoulding of polymeric microneedle arrays. We are currently carrying out an extensive OCTinformed study investigating the influence of microneedle array geometry on skin penetration depth, with a view to enhanced transdermal drug delivery from optimised laser-engineered Gantrez® AN-139 microneedles.

Microfabrication of dissolvable, swellable, and biodegradable polymeric microneedle arrays (MNs) were extensively investigated based in a nano sensitive fabrication style known as micromilling that is then combined with conventional micromolding technique. The aim of this study was to describe the polymer selection, and optimize formulation compounding parameters for various polymeric MNs. Inverse replication of micromilled master MNs reproduced with polydimethylsiloxane (PDMS), where solid out of plane polymeric MNs were subsequently assembled, and physicochemically characterized. Dissolvable, swellable, and biodegradable MNs were constructed to depth of less than 1 mm with an aspect ratio of 3.6, and 1/2 mm of both inter needle tip and base spacing. Micromolding step also enabled to replicate the MNs very precisely and accurate. Polymeric microneedles (MN) precision was ranging from ±0.18 to ±1.82% for microneedle height, ±0.45 to ±1.42% for base diameter, and ±0.22 to ±0.95% for interbase spacing. Although dissolvable sodium alginate MN showed less physical robustness than biodegradable polylactic-co-glycolic acid MN, their thermogravimetric analysis is of promise for constructing these polymeric types of matrix devices.

BackgroundThe “poke and release” strategy for the delivery of macromolecules using polymeric microneedle (MN) is of great importance because it eliminates microneedle reuse, the risks of biohazardous sharps and cross contamination, and it requires no special disposal mechanism. The main objective of this study was the determination of the stability and delivery of bovine serum albumin (BSA) that was transported across human skin via sodium alginate (SA) microneedle arrays (MNs) and SA needle free patches using two different analytical methods.Methodology and FindingsThe capability of two analytical methods, the bicinchoninic acid (BCA) assay and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), to precisely detect and quantify BSA within different types of polymeric MNs was assessed. The ex vivo protein release of BSA across dermatomed human abdominal skin from 10 w/w SA MNs was compared to that from needle-free patches using Franz diffusion cells. The developed applicator was mechanically characterized using a Texture Analyzer. The patch mold and its components were fabricated using a rapid prototyping machine.Conclusions/SignificanceThe BCA method was able to precisely detect BSA that had been loaded into SA MNs. However, the use of SDS-PAGE as the analytical method resulted in significantly different amounts of BSA recovered from differently conditioned polymeric MNs. The permeation of BSA across dermatomed human abdominal skin by SA MNs, which were composed of 100 pyramidal needles, increased by approximately 15.4 fold compared to the permeation obtained with SA needle-free patches. The ease of use of the applicator during the release studies was also demonstrated, as was its mechanical characterization.

Perhaps the greatest barrier to development of the field of transmembrane drug delivery is that only a limited number of drugs are amenable to administration by this route. The highly lipophilic nature and barrier function of the uppermost layer of the skin, the stratum corneum, for example, restricts the permeation of hydrophilic, high molecular weight and charged compounds into the systemic circulation. Other membranes in the human body can also present significant barriers to drug permeation. In order to successfully deliver hydrophilic drugs, and macromolecular agents of interest, including peptides, DNA and small interfering RNA, many research groups and pharmaceutical companies Worldwide are focusing on the use of microporation methods and devices. Whilst there are a variety of microporation techniques, including the use of laser, thermal ablation, electroporation, radiofrequency, ultrasound, high pressure jets, and microneedle technology, they share the common goal of enhancing the permeability of a biological membrane through the creation of transient aqueous transport pathways of micron dimensions across that membrane. Once created, these micropores are orders of magnitude larger than molecular dimensions and, therefore, should readily permit the transport of hydrophilic macromolecules. Additionally, microporation devices also enable minimally-invasive sampling and monitoring of biological fluids. This review deals with the innovations relating to microporation-based methods and devices for drug delivery and minimally invasive monitoring, as disclosed in recent patent literature.

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