An official website of the United States government
Microneedles are micron-sized devices that are used for the transdermal administration of a wide range of active pharmaceutics substances with minimally invasive pain. In the past decade, various additive manufacturing technologies have been used for the fabrication of microneedles; however, they have limitations due to material compatibility and bioavailability and are time-consuming and expensive processes. Additive manufacturing (AM), which is popularly known as 3D-printing, is an innovative technology that builds three-dimensional solid objects (3D). This article provides a comprehensive review of the different 3D-printing technologies that have the potential to revolutionize the manufacturing of microneedles. The application of 3D-printed microneedles in various fields, such as drug delivery, vaccine delivery, cosmetics, therapy, tissue engineering, and diagnostics, are presented. This review also enumerates the challenges that are posed by the 3D-printing technologies, including the manufacturing cost, which limits its viability for large-scale production, the compatibility of the microneedle-based materials with human cells, and concerns around the efficient administration of large dosages of loaded microneedles. Furthermore, the optimization of microneedle design parameters and features for the best printing outcomes is of paramount interest. The Food and Drug Administration (FDA) regulatory guidelines relating to the safe use of microneedle devices are outlined. Finally, this review delineates the implementation of futuristic technologies, such as artificial intelligence algorithms, for 3D-printed microneedles and 4D-printing capabilities.
more »
« less
Limpet Tooth‐Inspired Painless Microneedles Fabricated by Magnetic Field‐Assisted 3D Printing
Abstract Microneedle arrays show many advantages in drug delivery applications due to their convenience and reduced risk of infection. Compared to other microscale manufacturing methods, 3D printing easily overcomes challenges in the fabrication of microneedles with complex geometric shapes and multifunctional performance. However, due to material characteristics and limitations on printing capability, there are still bottlenecks to overcome for 3D printed microneedles to achieve the mechanical performance needed for various clinical applications. The hierarchical structures in limpet teeth, which are extraordinarily strong, result from aligned fibers of mineralized tissue and protein‐based polymer reinforced frameworks. These structures provide design inspiration for mechanically reinforced biomedical microneedles. Here, a bioinspired microneedle array is fabricated using magnetic field‐assisted 3D printing (MF‐3DP). Micro‐bundles of aligned iron oxide nanoparticles (aIOs) are encapsulated by polymer matrix during the printing process. A bioinspired 3D‐printed painless microneedle array is fabricated, and suitability of this microneedle patch for drug delivery during long‐term wear is demonstrated. The results reported here provide insights into how the geometrical morphology of microneedles can be optimized for the painless drug delivery in clinical trials.
more »
« less
- PAR ID:
- 10454728
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Functional Materials
- Volume:
- 31
- Issue:
- 5
- ISSN:
- 1616-301X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Microneedle (MN) technology is an optimal choice for the delivery of drugs via the transdermal route, with a minimally invasive procedure. MN applications are varied from drug delivery, cosmetics, tissue engineering, vaccine delivery, and disease diagnostics. The MN is a biomedical device that offers many advantages including but not limited to a painless experience, being time-effective, and real-time sensing. This research implements additive manufacturing (AM) technology to fabricate MN arrays for advanced therapeutic applications. Stereolithography (SLA) was used to fabricate six MN designs with three aspect ratios. The MN array included conical-shaped 100 needles (10 × 10 needle) in each array. The microneedles were characterized using optical and scanning electron microscopy to evaluate the dimensional accuracy. Further, mechanical and insertion tests were performed to analyze the mechanical strength and skin penetration capabilities of the polymeric MN. MNs with higher aspect ratios had higher deformation characteristics suitable for penetration to deeper levels beyond the stratum corneum. MNs with both 0.3 mm and 0.4 mm base diameters displayed consistent force–displacement behavior during a skin-equivalent penetration test. This research establishes guidelines for fabricating polymeric MN for high-accuracy and low-cost 3D printing.more » « less
-
null (Ed.)Microneedles provide a transdermal pathway for drug delivery, cosmetic infusion, vaccine administration, and disease diagnostics. Microneedle fabrication relies on the interplay of several variables which include design parameters, material properties, and processing conditions. In this research, our group explores the effect of design parameters and process variables for laser ablation of microneedles within a Polymethyl methacrylate (PMMA) mold. An Ytterbium laser (200W) was utilized to study the effect of five inputs factors (laser power, pulse width, number of repetitions, laser waveform, and interval time between laser pulses) on two output factors (diameter and height) of the fabricated microneedles. Polydimethylsiloxane (PDMS) polymer was cast within the PMMA microneedle mold. Scanning electron microscopy (SEM) was employed to image topographical features of the microneedles. Further, mechanical testing of the microneedles was conducted to evaluate the buckling load and deformation behavior of the microneedle array. A 20W pulse laser with trapezoidal waveform resulted in optimal microneedle topography with an aspect ratio of 1.2. ANOVA results (α = 0.05) depicted that laser power and number of repetitions were significant factors determining the geometrical features of the microneedle array. This research establishes a framework for the design and manufacturing of customized microneedles for precision medicine.more » « less
-
Biocompatible and biodegradable materials have been used for fabricating polymeric microneedles to deliver therapeutic drug molecules through the skin. Microneedles have advantages over other drug delivery methods, such as low manufacturing cost, controlled drug release, and the reduction or absence of pain. The study examined the delivery of amphotericin B, an antifungal agent, using microneedles that were fabricated using a micromolding technique. The microneedle matrix was made from GantrezTM AN-119 BF, a benzene-free methyl vinyl ether/maleic anhydride copolymer. The GantrezTM AN-119 BF was mixed with water; after water evaporation, the polymer exhibited sufficient strength for microneedle fabrication. Molds cured at room temperature remained sharp and straight. SEM images showed straight and sharp needle tips; a confocal microscope was used to determine the height and tip diameter for the microneedles. Nanoindentation was used to obtain the hardness and Young’s modulus values of the polymer. Load–displacement testing was used to assess the failure force of the needles under compressive loading. These two mechanical tests confirmed the mechanical properties of the needles. In vitro studies validated the presence of amphotericin B in the needles and the antifungal properties of the needles. Amphotericin B GantrezTM microneedles fabricated in this study showed appropriate characteristics for clinical translation in terms of mechanical properties, sharpness, and antifungal properties.more » « less
-
Biodegradable polymer microneedle (MN) arrays are an emerging class of transdermal drug delivery devices that promise a painless and sanitary alternative to syringes; however, prototyping bespoke needle architectures is expensive and requires production of new master templates. Here, we present a new microfabrication technique for MNs using fused deposition modeling (FDM) 3D printing using polylactic acid, an FDA approved, renewable, biodegradable, thermoplastic material. We show how this natural degradability can be exploited to overcome a key challenge of FDM 3D printing, in particular the low resolution of these printers. We improved the feature size of the printed parts significantly by developing a post fabrication chemical etching protocol, which allowed us to access tip sizes as small as 1 μm. With 3D modeling software, various MN shapes were designed and printed rapidly with custom needle density, length, and shape. Scanning electron microscopy confirmed that our method resulted in needle tip sizes in the range of 1–55 μm, which could successfully penetrate and break off into porcine skin. We have also shown that these MNs have comparable mechanical strengths to currently fabricated MNs and we further demonstrated how the swellability of PLA can be exploited to load small molecule drugs and how its degradability in skin can release those small molecules over time.more » « less
