Dissolving Microneedle Array Patches Manufactured By Solvent Casting Technique and Essential Characterization of Microneedle-Based Biomedical Devices

Our research mainly focuses on the optimization of a skin drug delivery using nano and microsystems, such as microneedle based devices. This study offers a feasible and reproducible method for preparing dissolving microneedles. To begin, prepare the aqueous colloidal dispersion of the constituent materials of DMAPs, by dissolving them in the appropriate amount of water.

Stir the mixture vigorously to obtain a uniform dispersion. Allow the polymers to stir minimally overnight to achieve complete dispersion, and let the air bubbles disperse during this prolonged stirring period. If air bubbles persist, centrifuge the polymeric dispersion at 1000 G for five minutes at 25 degrees Celsius.

Add the cargo at the desired concentration into the polymeric dispersion, and stir the mixture moderately until it becomes homogeneous without incorporating new air bubbles. Now, to accommodate the molds into the wells, use modeling clay or dental cement, and dispose the PDMS molds into the 12 well plate. Next, cast 20 microliters of the drug loaded polymeric blend onto the PDMS molds.

Place the plate in the centrifuge, and spin at 3000 G for five minutes at 25 degrees Celsius. Now, turn the plate 180 degrees, and repeat the centrifugation to ensure filling of all needle-like cavities. Then, using a pipette, carefully remove the excess drug loaded polymeric dispersion from the molds.

Dry the drug loaded polymeric dispersion in the molds by placing them under vacuum at 600 millibars for 30 minutes at 25 degrees Celsius. Prepare a highly concentrated polymeric dispersion free of drugs to form the base plate of the DMAP's device. Ensure the dispersion is homogeneous before use.

Next, cast 50 microliters of the drug free polymeric dispersion onto the PDMS molds. Place the plate in the centrifuge and spin twice, including a midpoint plate rotation of 180 degrees. After centrifugation, add 100 microliters of dispersion to each mold, followed by an additional 50 microliters to the base plate after 12 hours.

Leave the DMAPs in the PDMS molds to dry for three to five days at room temperature in a dry seal desiccater. Demold the DMAPs carefully from the PDMS molds using forceps. Alternatively, peel the DMAPs off the molds using scotch cellulose tape.

For the positive pressure method, cast 150 microliters of the drug loaded polymeric blend onto the PDMS molds, and place them in a pressure tank. Fill the pressure tank with air until it reaches a pressure between three and four bar. Maintain this pressure for at least 15 minutes.

Visualize the DMAPs using a micro camera with appropriate magnification to distinguish the needle-like projections. Adjust the focus to clearly resolve individual microneedles. Next, attach the DMAPs to a support device to visualize the morphology, and length of the microneedle-like projections by optical microscopy.

Evaluate the mechanical properties of the DMAPs by placing the device into a commercially available DMAPs applicator. Compress the applicator against a stainless steel flat surface for 30 seconds. After compression, record the length of the microneedle-like projections and calculate the deformation percentage by comparing the length before and after compression.

Then, determine the preliminary insertion capacity of the DMAPs using a surrogate artificial skin method based on thermoplastic sheets made of olefin type material. Compress the DMAPs device against eight bound sheets using the same compression conditions applied to the stainless steel surface. Now, determine the ex vivo insertion capacity of the DMAPs using human, porcine, or rodent skin explants that have been previously excised and carefully trimmed.

Clean the skin explant by soaking it in abundant water for one to two minutes. Place the clean skin explant onto an aluminum foil wrapped foam material with the stratum corneum side facing upwards. Proceed with insertion using the same compression conditions previously described.

Leave the DMAPs inserted into the skin until dissolution of the microneedle tips occurs, and observe the device remaining in contact with the skin during dissolution. Determine the ex vivo drug skin deposition and absorption using a Franz-Diffusion cell setup. Prepare the skin explant using the previously described trimming and cleaning procedure, and insert the DMAPs into the skin structure for 30 seconds.

Glue the donor chamber of the Franz-Diffusion cell to the skin using an appropriate amount of cyanoacrylate. Allow the adhesive to dry completely, then attach the skin donor chamber complex to the receptor chamber using a appropriate clamps. Finally, proceed with sampling according to the standard diffusion cell protocol.

Manufactured DMAPs displayed a homogeneous appearance with successful formation of microneedle-like projections, and the color dye was localized within the projections, with the base plate remaining free of drugs. Optical microscopy revealed that microneedle-like projections had sharp tip ends and no deformation before compression. After compression, microneedle-like projections showed visible deformation of structure.

In an artificial skin model, DMAPs successfully penetrated the thermoplastic sheet, creating visible holes. The number of holes created in different layers of the thermoplastic model correlated with microneedle insertion depth. Ex-vivo murine skin explants showed progressive dying of the inner skin layers after insertion, consistent with DMAP dissolution over time.

Histological examination with Eosin hematoxylin staining, confirmed insertion of microneedle-like projections into skin sections. A Franz-Diffusion cell setup was used to evaluate the diffusion of drugs through skin explants, with clear visualization of the donor chamber, skin, and receptor chamber. This protocol provides a foundational guideline for fabricating dissolving microneedle devices, enabling researchers to explore their design, performance and biomedical application potential.

A key challenge is ensuring cargo compatibility with the polymer matrix. Certain cargoes may interfere with the material properties or compromise microneedle performance. Future studies can adapt this protocol to specific drugs and polymers, optimizing microneedles preparation, and expanding applications across therapeutic and biomedical uses.