Delivery of Niacinamide to the Skin Using Microneedle-Like Particles

Abstract

The stratum corneum is the outermost skin layer that obstructs the delivery of active ingredients found in cosmeceutical products. Chemical peels and microbeads have been used to overcome this layer, but these methods can cause side effects and are not environmentally friendly. While microneedles do not share the dangers mentioned above, they are currently only available as patches, which makes them unsuitable to be used with products that are usually applied onto a large area of the skin surface. Therefore, the aim of this study was to develop microneedle-like particles (MLP) whose needles would disrupt the skin during the rubbing process. A modified approach taken from conventional micromolding techniques was used to make the MLPs. The experimental results show that the fabricated structures had the required mechanical strength. Furthermore, after the application of the MLPs, the permeability of two fluorescent dyes, fluorescein sodium salt and sulforhodamine B increased to 217.6% ± 25.6% and 251.7% ± 12.8% respectively. Additionally, the permeability of a model drug, niacinamide, was shown to have increased to 193.8% ± 29.9%. Cryosectioned porcine slices also confirmed the ability of MLPs to enhance skin permeability by revealing a deeper penetration of the applied fluorescent dye. Altogether, the results demonstrate the potential of MLPs to be used as safe skin permeability enhancers that can be applied all over the skin.

Keywords: cosmeceutical; microneedle; microparticle; niacinamide; transdermal drug delivery.

Figure 1

3D Computer-aided design (CAD) images of the designed MLP displaying the (a) side view, (b) top view, (c) and overall view. Each MLP had a height of 300 μm, a base length of 450 μm, a needle length of 150 μm, and a tip diameter of 30 μm.

Figure 2

Fabrication process of the MLPs. (a) h-PDMS is poured onto the positive steel mold. (b) The cured h-PDMS negative mold is removed. (c) The negative h-polymethylsiloxane (PDMS) mold is filled with a polymer mixture via vacuum and then dried. (d) The PMMA solution in the ethyl acetate is spread on top of the h-PDMS mold and left to evaporate. (e) The dried PMMA film is removed from the mold and peeled off along with the dried MLPs. (f) The PMMA film is submerged in ethyl acetate for dissolution. (g) Needles are freed from the PMMA film and recovered from the ethyl acetate. Images created using SolidWorks (SolidWorks 2015, Dassault Systèmes, Vélizy-Villacoublay, France).

Figure 3

MLP array loaded with SRB (a) observed by stereo microscopy. The array contained 121 MLPs (11 × 11) in an area of 1 cm². The MLPs were (b) removed from the h-PDMS mold by peeling off the PMMA film. The film was then (c) dissolved in ethyl acetate, and the freed MLPs were collected.

Figure 4

Force travel-curve of the MLPs.

Figure 5

Relative skin permeability of (a) sulforhodamine B (SRB) and (b) fluorescein sodium salt (FSS) after applying 1200 MLPs for 30 and 60 s (means ± SD, n = 3).

Figure 6

Relative skin permeability of niacinamide after (a) applying 1200 MLPs for 30 and 60 s. The same experiment was performed again using niacinamide to determine the relative skin permeability after (b) applying 300 and 600 MLPs for 30 s (means ± SD, n = 3).

Figure 7

Histological images of cryosectioned porcine skin after SRB dye application. Dye distribution of (a) MLP untreated and (b) MLP treated porcine skin observed under fluorescent microscope.