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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.
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Biodegradable 3D printed polymer microneedles for transdermal drug delivery
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.
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- Award ID(s):
- 1654405
- PAR ID:
- 10083668
- Date Published:
- Journal Name:
- Lab on a Chip
- Volume:
- 18
- Issue:
- 8
- ISSN:
- 1473-0197
- Page Range / eLocation ID:
- 1223 to 1230
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract ObjectiveThe 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. MethodsCBD 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 findingsMicroscopic 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). ConclusionOverall, systemic absorption of CBD was significantly enhanced using 3D-printed MN drug delivery system.more » « less
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Purpose This paper aims to study the mass loss of three-dimensional (3D) printed materials at high temperatures. A preconcentration and analysis technique, static headspace gas chromatography-mass spectrometry (SHS-GC-MS), is demonstrated for the analysis of volatile compounds liberated from fused deposition modeling (FDM) and stereolithography (SLA) 3D printed models under elevated temperatures. Design/methodology/approach A total of seven commercial 3D printing materials were tested using the SHS-GC-MS approach. The printed model mass and mass loss were examined as a function of FDM printing parameters including printcore temperature, model size and printing speed, and the use of SLA postprocessing procedures. A high temperature resin was used to demonstrate that thermal degradation products can be identified when the model is incubated under high temperatures. Findings At higher printing temperatures and larger model sizes, the initial printed model mass increased and showed more significant mass loss after thermal incubation for FDM models. For models produced by SLA, the implementation of a postprocessing procedure reduced the mass loss at elevated temperatures. All FDM models showed severe structural deformation when exposed to high temperatures, while SLA models remained structurally intact. Mass spectra and chromatographic retention times acquired from the high temperature resin facilitated identification of eight compounds (monomers, crosslinkers and several photoinitiators) liberated from the resin. Originality/value The study exploits the high sensitivity of SHS-GC-MS to identify thermal degradation products emitted from 3D printed models under elevated temperatures. The results will aid in choosing appropriate filament/resin materials and printing mechanisms for applications that require elevated temperatures.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/c8lc00098k
