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.
Microneedle (MN) technology offers a powerful approach for transdermal delivery enabling painless injection and facilitating self‐administration without the need for professional assistance. However, the weak mechanical strength of MNs can lead to inefficient drug delivery and serious skin irritation if the MNs fracture during administration and leave fragments under the skin. Thus, the MNs need to be mechanically robust to avoid fracture during penetration through the skin while maintaining efficient drug delivery. Herein, the polymer‐based MNs with layer‐by‐layer (LbL) films of silica (SiO2) nanoparticles (NPs) and a polycation (poly(diallyldimethylammonium chloride) (PDADMAC)) followed by hydrothermal calcination are reinforced. The mechanical strength of the MNs is significantly improved after LbL assembly and shows lower threshold pressure to penetrate skins. Moreover, their drug loading and releasing properties are significantly enhanced due to an increase in the surface area and interfacial interaction. These SiO2nanoparticle‐containing LbL thin films have great potential for the surface modification of 3D microstructured devices such as MNs, as evidenced by their enhanced mechanical strength and drug coating efficiency that result in a promising MN drug delivery model.
more » « less- Award ID(s):
- 1945841
- PAR ID:
- 10516534
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Materials Interfaces
- ISSN:
- 2196-7350
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Objective The objective of the present study was to enhance the bioavailability of cannabidiol (CBD) using 3D Digital Light Processing (DLP)-printed microneedle (MN) transdermal drug delivery system.
Methods CBD MN patch was fabricated and optimized using 3D DLP printing using CBD (8% w/v), Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) (0.49% w/v), distilled water (20% w/v), and poly (ethylene glycol) dimethacrylate 550 (PEGDAMA 550) (up to 100% w/v). CBD MNs were characterized for their morphology, mechanical strength, in vitro release study, ex vivo permeation study, and in vivo pharmacokinetic (PK) profile.
Key findings Microscopic images showed that sharp CBD MNs with a height of ~800 μm, base diameter of ~250 μm, and tip with a radius of curvature (RoC) of ~15 μm were successfully printed using optimized printing parameters. Mechanical strength studies showed no significant deformation in the morphology of CBD MNs even after applying 0.5N/needle force. Ex vivo permeation study showed significant (P < .0001) permeation of CBD in the receiving media as compared to CBD patch (control). In vivo PK study showed significantly (P < .05) enhanced bioavailability in the case of CBD MN patch as compared to CBD subcutaneous inj. (control).
Conclusion Overall, systemic absorption of CBD was significantly enhanced using 3D-printed MN drug delivery system.
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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
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Microneedles (MNs) are micrometer-sized arrays that can penetrate the skin in a minimally invasive manner; these devices offer tremendous potential for the transdermal delivery of therapeutic molecules. Although there are many conventional techniques for manufacturing MNs, most of them are complicated and can only fabricate MNs with specific geometries, which restricts the ability to adjust the performance of the MNs. Herein, we present the fabrication of gelatin methacryloyl (GelMA) MN arrays using the vat photopolymerization 3D printing technique. This technique allows for the fabrication of high-resolution and smooth surface MNs with desired geometries. The existence of methacryloyl groups bonded to the GelMA was verified by 1 H NMR and FTIR analysis. To examine the effects of varying needle heights (1000, 750, and 500 µm) and exposure times (30, 50, and 70 s) on GelMA MNs, the height, tip radius, and angle of the needles were measured; their morphological and mechanical properties were also characterized. It was observed that as the exposure time increased, the height of the MNs increased; moreover, sharper tips were obtained and tip angles decreased. In addition, GelMA MNs exhibited good mechanical performance with no breakage up to 0.3 mm displacement. These results indicate that 3D printed GelMA MNs have great potential for transdermal delivery of various therapeutics.more » « less
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