Analyzing polymeric matrix for fabrication of a biodegradable microneedle array to enhance transdermal delivery

Abstract

Traditional drug delivery systems, using invasive, transdermal, and oral routes, are limited by various factors, such as the digestive system environment, skin protection, and sensory nerve stimulation. To improve the drug delivery system, we fabricated a polysaccharide-based, dissolvable microneedle-based array, which combines the advantages of both invasive and transdermal delivery systems, and promises to be an innovative solution for minimally invasive drug delivery. In this study, we designed a reusable aluminum mold that greatly improved the efficiency and convenience of microneedle fabrication. Physical characterization of the polysaccharides, individual or mixed at different ratios, was performed to identify a suitable molecule to fabricate the dissolvable microneedle. We used a vacuum deposition-based micro-molding method at low temperature to fabricate the model. Using a series of checkpoints from material into product, a systematic feedback mechanism was built into the "all-in-one" fabrication step, which helped to improve production yields. The physical properties of the fabricated microneedle were assessed. The cytotoxicity analysis and animal testing of the microneedle demonstrated the safety and compatibility of the microneedle, and the successful penetration and effective release of a model protein.

Advances of Microneedles in Biomedical Applications

“…Hwa et al had determined the appropriate viscosity by observing the flow condition of different concentrations of CMC in the test tubes. After choosing 3% CMC, the solutions were centrifuged, poured into molds and placed in a vacuum (65 °C, 24 h) [ 50 ]. After filling in the mold, vacuum or centrifugation was applied to avoid the constraints of surface tension and viscosity of the solution, which require more steps in the micromolding processes.…”

“…Polymers are highly viscous, not prone to fracture, and are mostly biocompatible and suitable for low-cost mass production [49], which has been extensively used to fabricate microneedles for biomedical applications. Several biocompatible materials have been developed for microneedle fabrication, such as carboxymethyl cellulose (CMC) [50], PVA, polyvinylpyrrolidone (PVP), poly (lactic-co-glycolic acid) (PLGA) [51], hyaluronic acid (HA), methacrylated hyaluronic acid (MeHA) [52] and so on. Mao et al loaded poorly water-soluble rapamycin into PVP MN, as PVP can help rapamycin dissolve quickly in the body.…”

Hydrophobicity Tuning by the Fast Evolution of Mold Temperature during Injection Molding

“…These methods can be applied to a wide range of material, and are suitable for mass production of micro and nano-structured surfaces [15,18]. In particular, the “replica molding” techniques consist in the replication of a master, produced by lithography-based techniques, by hot embossing or injection molding [16,19]. The latter surely presents the advantage of cheaper and faster production [20,21,22,23,24].…”