Microneedle Arrays Allow Lower Microbial Penetration Than Hypodermic Needles In Vitro

Abstract

Methods-In this study we determined, for the first time, the ability of microorganisms to traverse microneedle-induced holes using two different in vitro models.Results-When employing Silescol® membranes, the numbers of Candida albicans, Pseudomonas aeruginosa and Staphylococcus epidermidis crossing the membranes were an order of magnitude lower when the membranes were punctured by microneedles rather than a 21G hypodermic needle. Apart from the movement of C. albicans across hypodermic needle-punctured membranes, where 40.2% of the microbial load on control membranes permeated the barrier over 24 h, the numbers of permeating microorganisms was less than 5% of the original microbial load on control membranes. Experiments employing excised porcine skin and radiolabelled microorganisms showed that the numbers of microorganisms penetrating skin beyond the stratum corneum were approximately an order of magnitude greater than the numbers crossing Silescol® membranes in the corresponding experiments. Approximately 10 3 cfu of each microorganism adhered to hypodermic needles during insertion. The numbers of microorganisms adhering to MN arrays were an order of magnitude higher in each case. Conclusion-We have shown here that microneedle puncture resulted in significantly less microbial penetration than did hypodermic needle puncture and that no microorganisms crossed the viable epidermis in microneedle-punctured skin, in contrast to needle-punctured skin. Given the antimicrobial properties of skin, it is, therefore, likely that application of microneedle arrays to skin in an appropriate manner would not cause either local or systemic infection in normal circumstances in immune-competent patients. In supporting widespread clinical use of microneedle-based delivery systems, appropriate animal studies are now needed to conclusively demonstrate this in vivo. Safety in patients will be enhanced by aseptic or sterile manufacture and by fabricating microneedles from self-disabling materials (e.g. dissolving or biodegradable polymers) to prevent inappropriate or accidental reuse.

Microneedle Manufacture: Assessing Hazards and Control Measures

“…There are five principal classes of microneedle used for drug delivery applications: solid, drug coated solid, hollow, dissolvable, and swellable [1][2][3][8][9][10][11][12][13][14][15][16][17][18][19]. The fabrication of solid MN arrays is procedurally the simplest approach and can be constructed from a variety of conventional and inexpensive polymers such as polystyrene, polycarbonate, and polymethylmethacrylate [8][9][10][11][12].…”

“…The fabrication of solid MN arrays is procedurally the simplest approach and can be constructed from a variety of conventional and inexpensive polymers such as polystyrene, polycarbonate, and polymethylmethacrylate [8][9][10][11][12]. Such polymers enable the acquisition of mechanically robust arrays that can withstand repeated handling by inexpert users, but the retention of the "sharp" aspect can inadvertently present a needlestick hazard where such devices are carelessly discarded within the workspace.…”

“…In the case of manufacturing laboratories, the assumption is that any application to human skin occurs as a result of accident and that there will therefore be no prior treatment. It has been shown that the potential for bacterial infection arising from microneedle applications is considerably lower when compared with conventional injection systems [9,28], and, under non-occlusive conditions, the microchannels would be expected to heal within 2 h of the initial puncture [29]. The situation becomes more ambiguous where there is a failure in the dissolution or removal of a dissolvable/swellable microneedle such that partially dissolved needle fragments continue to bridge the skin barrier [1].…”

Potential of biodegradable microneedles as a transdermal delivery vehicle for lidocaine

“…Most literature suggests that pathogenic infections are not caused by using microneedles (Arora et al 2008;Donnelly et al 2009;Han et al 2012). The removal of microneedles leaves indents on the skin and the main factors, such as microneedle length, number in an array and microneedle cross-sectional area, effect the time for natural skin resealing (Gupta et al 2011).…”

Permeation of antigen protein-conjugated nanoparticles and live bacteria through microneedle-treated mouse skin

“…[30][31][32][33] The first study on the ability of microbes to traverse microneedle-induced micropores was reported by Donnelly et al, whereby permeation of microbes through porcine skin pretreated with a microneedle array (280 µm long, base diameter 250 µm) was confirmed in vitro. 34 In the present study, an ex vivo model was designed to evaluate permeation of live bacteria through a mouse skin area pretreated with microneedles of different sizes. A nonpathogenic Escherichia coli DH5α strain was used for this study.…”