Polymeric Microneedles Enhance Transdermal Delivery of Therapeutics

This research presents the efficacy of polymeric microneedles in improving the transdermal permeation of methotrexate across human skin. These microneedles were fabricated from PLGA Expansorb^® 50-2A and 50-8A and subjected to comprehensive characterization via scanning electron microscopy, Fourier-transform infrared spectroscopy, and mechanical analysis. We developed and assessed a methotrexate hydrogel for physicochemical and rheological properties. Dye binding, histological examinations, and assessments of skin integrity demonstrated the effective microporation of the skin by PLGA microneedles.

We measured the dimensions of microchannels in the skin using scanning electron microscopy, pore uniformity analysis, and confocal microscopy. The skin permeation and disposition of methotrexate were researched in vitro. PLGA 50-8A microneedles appeared significantly longer, sharper, and more mechanically uniform than PLGA 50-2A needles. PLGA 50-8A needles generated substantially more microchannels, as well as deeper, larger, and more uniform channels in the skin than PLGA 50-2A needles. Microneedle insertion substantially reduced skin electrical resistance, accompanied by an elevation in transepidermal water loss values.

PLGA 50-8A microneedle treatment provided a significantly higher cumulative delivery, flux, diffusion coefficient, permeability coefficient, and predicted steady-state plasma concentration; however, there was a shorter lag time than for PLGA 50-2A needles, base-treated, and untreated groups (p < 0.05). Conclusively, skin microporation using polymeric microneedles significantly improved the transdermal delivery of methotrexate.

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Materials

Poly(lactic-co-glycolic acid) (PLGA) with a 1:1 lactide/glycolide ratio and terminal carboxylic acid groups (–COOH) was generously provided by Merck kGaA (Frankfurter Strasse, Darmstadt, Germany). Two PLGA grades were employed in this study: Expansorb ® DLG 50-2A with a molecular weight of 5–20 kDa and Expansorb® DLG 50-8A with a molecular weight of 80–130 kDa. Methotrexate and Carbopol® 980 NF were obtained from Sigma Aldrich, St. Louis, MO, USA, and Lubrizol Corporation, Wickliffe, OH, USA, respectively. Phosphate-buffered saline (PBS) was obtained from Fisher BioReagent (Fair Lawn, NJ, USA) at a concentration of 0.1 M and a pH of 7.4 ± 0.1. Eastman Kodak Company (Rochester, NY, USA) supplied the methylene blue dye. A 0.35% fluorescent solution (Fluoresoft®) was purchased from Holles Laboratories Inc. in Cohasset, MA, USA. The remainder of the reagents were of analytical grade. CuDerm (Dallas, TX, USA) supplied the D-Squame D101 stripping discs, while Dynarex produced the cotton tipped applicators (Orangeburg, NY, USA). The Sylgard® 186 silicone elastomer base and curing agent employed in this study were provided by Dow Corning Corporation (Midland, MI, USA). Micropoint Technologies Pte Ltd. supplied the master structure (a microneedle array consisting of 10 × 10 solid stainless-steel pyramidal-shaped needles with a 500 μm length, 150 μm × 150 μm base dimensions, and 500 μm inter-needle spacing) (Singapore). Human skin (posterior torso area of 48-year-old female) was acquired from New York Fire Fighter skin bank (Brooklyn, NY, USA). De-identified human skin was used under a protocol exempted by Mercer University Institutional Review Board (H0303041). Employing a calibrated material thickness gauge (Electromatic Equipment Co., Inc., Cedarhurst, NY, USA) with a measurement range of 0 to 25 mm, we determined the average thickness of 16 skin samples at 0.31 ± 0.06 mm. Until use, the skin pieces were cryopreserved in sealed containers in a freezer (–80 °C).

Nguyen, H.X.; Kipping, T.; Banga, A.K. Polymeric Microneedles Enhance Transdermal Delivery of Therapeutics. Pharmaceutics 2024, 16, 845. https://doi.org/10.3390/pharmaceutics16070845

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