Fabrication of Circular Obelisk-Type Multilayer Microneedles Using Micro-Milling and Spray Deposition

Abstract

In this study we present the fabrication of multilayer microneedles with circular obelisk and beveled-circular obelisk geometries, which have potential applications in implantable drug delivery devices. Micro-milling was adopted as an environmental-friendly and cost-effective way to fabricate primary metal microneedle masters. Polylactic acid (PLA) microneedles with sharp tips were then obtained by micromolding followed by oxygen plasma etching and used for preparing polydimethylsiloxane (PDMS) microneedle molds. A spray deposition process was employed for microneedle fabrication to facilitate the formation of multilayer microneedles while helping in maintenance of drug stability. Multilayer microneedles were successfully formed by sequential spraying of poly(lactic-co-glycolic acid) (PLGA) and polyvinylpyrrolidone (PVP) solutions into the mold. The fabricated PLGA-PVP multilayer microneedles penetrated the pig cadaver skin without breakage and released dyes in the skin at different rates, which reveals the potential for implantable microneedles enabling controlled release. Mechanical testing demonstrated that the obelisk-shaped microneedles were mechanically stronger than a pyramid-shaped microneedle and suggested that strong adhesion between PLGA and PVP layers was achieved as well. Structural stability and functionality of a model drug, horseradish peroxidase (HRP), upon spray deposition was examined using circular dichroism (CD) spectroscopy and enzyme activity assay. HRP retained its secondary structure and activity in PVP, whereas HRP in PLGA showed structural changes and reduced activity. Combination of micro-milling and spray deposition would be an attractive way of fabricating drug-containing polymer microneedles with various geometries while reducing prototyping time and process-induced drug instability.

Micro-Pillar Integrated Dissolving Microneedles for Enhanced Transdermal Drug Delivery

“…Over the past decade, numerous studies have focused on improving the delivery efficiency of DMNs [31,32,33]. Two-layered and arrowhead DMNs, comprised of a non-drug-loaded polymer layer at the bottom and a drug-encapsulated tip, have been introduced to improve drug delivery efficiency compared with traditional DMNs.…”

Progress in Microneedle-Mediated Protein Delivery

“…Then, after mold fabrication, microneedles can be replicated on it. MN masters are usually produced by techniques such as photolithography using deep X-ray lithography of Lithographie Galvanoformung Abformung [13,16] and ultraviolet (UV) lithography [17], laser ablation [18], micromilling and microgrinding [19,20], additive manufacturing [21,22], laser percussion drilling [13,16], and deep reactive ion etching (DRIE) [23]. The produced master can be re-used to make multiple molds, and each mold can be used several times for MN fabrication after appropriate cleaning.…”

“…Long evaporation times may compromise the activity of the protein, in addition to being economically expensive [33]. Alternatively, spray coating can be used to deposit polymer solutions into MN molds [20,34] in a faster and safer way for the protein. Finally, the solution in the mold is left to become dry to ensure complete evaporation of the solvent.…”

Live Vaccinia Virus-Coated Microneedle Array Patches for Smallpox Vaccination and Stockpiling

“…A microneedle master, composed of 97 obelisk microneedles (800 µm height, 370 µm width, 400 µm gap between needles) in a circular base (1 cm diameter), was prepared by micromilling [35]. A microneedle mold was prepared by casting polydimethylsiloxane (PDMS, Sylgard ® 184; Dow Corning, Midland, MI, USA) over the master followed by curing at 70 • C for 1 h. Polymeric microneedles were subsequently replicated through casting polylactic acid (PLA; DURECT Corp., Birmingham, AL, USA) into the mold.…”