Journal: Molecular Therapy. Nucleic Acids

Article Title: Gene Silencing in Skin After Deposition of Self-Delivery siRNA With a Motorized Microneedle Array Device

doi: 10.1038/mtna.2013.56

Figure Lengend Snippet: Handheld motorized microneedle array device . ( a ) The inner reservoir of the motorized microneedle array cartridge contains 300 µl of a red dye solution for visualization. ( b ) The needles can be adjusted for penetration depth and are set here at 0.1 mm to protrude slightly beyond the edge of the chamber. ( c ) Channels located between the needles allow flow of solution onto the surface of the skin during treatment.

Article Snippet: Microneedles represent an efficient way to deliver large charged cargos including siRNAs across the primary barrier, the stratum corneum, and are generally regarded as less painful than conventional hypodermic needles., , Motorized “stamp type” microneedle devices, including the motorized microneedle array (MMNA) device used in this study, have been shown to be safe in hairless mice studies and cause little or no pain as evidenced by (i) widespread use in the cosmetic industry and (ii) limited testing in which nearly all volunteers found use of the device to be much less painful than a flushot (TransDerm, data on file), suggesting siRNA delivery using this device will result in much less pain than was experienced in the previous clinical trial using hypodermic needle injections.

Techniques:

Journal: Molecular Therapy. Nucleic Acids

Article Title: Gene Silencing in Skin After Deposition of Self-Delivery siRNA With a Motorized Microneedle Array Device

doi: 10.1038/mtna.2013.56

Figure Lengend Snippet: Cy3-labeled sd-siRNA distribution in mouse and human skin . Mouse or human skin was treated with the motorized microneedle array device loaded with 50 µl of 0.1 mg/ml Cy3-labeled sd-siRNA and intradermally injected as described below. After a 1-hour incubation, skin was collected, frozen in optimum cutting temperature (OCT) compound, and sectioned (10 µm). ( a ) Sections of hairless mouse flank skin in which breaches in the epidermis are shown in their entirety using a ×5 objective. Intradermally injected skin (16 µl of 0.1 mg/ml Cy3-labeled sd-siRNA) was sectioned to the center of the injection site and similarly displayed. The individual images were stitched together using ICE software. ( b ) Magnification (×10) of treated skin. ( c ) Further magnification of images from ( b ) shows diffusion of the Cy3-labeled sd-siRNA in the epidermis originating from the needle penetration site (arrow). Left panels: 4′,6-diamidino-2-phenylindole and Cy3 overlay; right panels: Cy3 alone. ( d ) Distribution of fluorescently labeled sd-siRNA in human abdominoplasty skin. Skin breaches due to penetration of the motorized microneedles are seen in their entirety using a ×5 objective. Intradermally injected skin (50 µl of 0.1 mg/ml Cy3-labeled sd-siRNA) was similarly sectioned and imaged. ( e ) Magnification of treated skin. ( f ) Further magnification of the images from ( e ) shows diffusion of the Cy3-labeled sd-siRNA in the epidermis originating from the needle penetration site (arrow), whereas low levels of fluorescence are observed in the epidermis following intradermal injection. Left panels: 4′,6-diamidino-2-phenylindole, and Cy3 overlay; right panels: Cy3 alone. Nuclei are visualized by DAPI (blue). Scale bar = 200 µm.

Article Snippet: Microneedles represent an efficient way to deliver large charged cargos including siRNAs across the primary barrier, the stratum corneum, and are generally regarded as less painful than conventional hypodermic needles., , Motorized “stamp type” microneedle devices, including the motorized microneedle array (MMNA) device used in this study, have been shown to be safe in hairless mice studies and cause little or no pain as evidenced by (i) widespread use in the cosmetic industry and (ii) limited testing in which nearly all volunteers found use of the device to be much less painful than a flushot (TransDerm, data on file), suggesting siRNA delivery using this device will result in much less pain than was experienced in the previous clinical trial using hypodermic needle injections.

Techniques: Labeling, Injection, Incubation, Software, Diffusion-based Assay, Fluorescence

Journal: Molecular Therapy. Nucleic Acids

Article Title: Gene Silencing in Skin After Deposition of Self-Delivery siRNA With a Motorized Microneedle Array Device

doi: 10.1038/mtna.2013.56

Figure Lengend Snippet: Confocal fluorescence imaging of Cy3-labeled sd-siRNA in human skin. Following motorized microneedle array delivery (30–60 minutes) of 100 µl of 0.5 mg/ml Cy3-labeled sd-siRNA (in phosphate-buffered saline) to excised human facial skin, siRNA distribution was imaged (reflectance and red fluorescence) with a modified Lucid VivaScope (see Materials and Methods). ( a ) Reflectance imaging at 29-µm depth shows the primary penetration site for this individual needle (note arrow). ( b ) Fluorescence imaging at 59-µm depth shows the diffusion of labeled sd-siRNA through the epidermis. ( c ) Magnification of the boxed region in ( b ) shows the interaction of the labeled sd-siRNA with individual cells. Scale bar = 100 µm.

Article Snippet: Microneedles represent an efficient way to deliver large charged cargos including siRNAs across the primary barrier, the stratum corneum, and are generally regarded as less painful than conventional hypodermic needles., , Motorized “stamp type” microneedle devices, including the motorized microneedle array (MMNA) device used in this study, have been shown to be safe in hairless mice studies and cause little or no pain as evidenced by (i) widespread use in the cosmetic industry and (ii) limited testing in which nearly all volunteers found use of the device to be much less painful than a flushot (TransDerm, data on file), suggesting siRNA delivery using this device will result in much less pain than was experienced in the previous clinical trial using hypodermic needle injections.

Techniques: Fluorescence, Imaging, Labeling, Saline, Modification, Diffusion-based Assay

Journal: Molecular Therapy. Nucleic Acids

Article Title: Gene Silencing in Skin After Deposition of Self-Delivery siRNA With a Motorized Microneedle Array Device

doi: 10.1038/mtna.2013.56

Figure Lengend Snippet: Delivery of sd-siRNA strongly inhibits targeted reporter gene expression. Hairless tg-CBL/hMGFP mouse flank skin ( n = 3) was treated on days 0, 2, 4, 6, 8, and 10 with the MMNA device loaded with 100 µl of 5 mg/ml CBL3 sd-siRNA or nonspecific control sd-siRNA (sd-TD101). The mouse skin was marked to allow the same area of the flank to be treated for each administration. On day 11, the mice were killed and the treated skin was excised for RTqPCR analysis and fluorescence imaging. ( a ) Total RNA was isolated from the epidermis of the excised skin, reverse transcribed, and reporter (CBL/hMGFP) mRNA levels (relative to K14) were quantified in triplicate by qPCR. Bars indicate standard error. ( b ) Representative fluorescence images (bottom) with bright field overlay (top) of frozen skin sections (10 µm) prepared from treated mice show inhibition of hMGFP fluorescence signal in the skin treated with specific sd-siRNA over control sd-siRNA. Nuclei are visualized by DAPI (blue). Scale bar is 100 µm.

Article Snippet: Microneedles represent an efficient way to deliver large charged cargos including siRNAs across the primary barrier, the stratum corneum, and are generally regarded as less painful than conventional hypodermic needles., , Motorized “stamp type” microneedle devices, including the motorized microneedle array (MMNA) device used in this study, have been shown to be safe in hairless mice studies and cause little or no pain as evidenced by (i) widespread use in the cosmetic industry and (ii) limited testing in which nearly all volunteers found use of the device to be much less painful than a flushot (TransDerm, data on file), suggesting siRNA delivery using this device will result in much less pain than was experienced in the previous clinical trial using hypodermic needle injections.

Techniques: Gene Expression, Control, Fluorescence, Imaging, Isolation, Reverse Transcription, Inhibition

Journal: ACS Omega

Article Title: Machine Learning-Enabled Optimization of Interstitial Fluid Collection via a Sweeping Microneedle Design

doi: 10.1021/acsomega.3c01744

Figure Lengend Snippet: Parameters Defining the Geometry of a Single Microneedle and Number of Variations Used in COMSOL Multiphysics

Article Snippet: A single default design for a microneedle was created in a COMSOL environment with the dimensions shown in Figure .

Techniques: Control

Journal: Pharmaceutics

Article Title: Potential of Microneedle Systems for COVID-19 Vaccination: Current Trends and Challenges

doi: 10.3390/pharmaceutics14051066

Figure Lengend Snippet: Comparison of syringe and MN vaccination.

Article Snippet: 7. , Nanopass (Microjet TM ) , Silicon microneedles , Influenza, Polio, Varicella-Zoster, cancers, Hepatitis B, and COVID-19.

Techniques: Comparison

Journal: Pharmaceutics

Article Title: Potential of Microneedle Systems for COVID-19 Vaccination: Current Trends and Challenges

doi: 10.3390/pharmaceutics14051066

Figure Lengend Snippet: dMN manufacturing methods (taken from ) Micromolding with a polydimethylsiloxane (PDMS) mold is the most prevalent method for producing dMNs. Drawing lithography operates by extending two-dimensional polymeric material into a three-dimensional shape. Longitudinal extension of molten polymer by pillaring higher moving plate. In soft lithography , dMNs are produced by (A) heating a polymer sheet and a mold with microcavities. (B) The filled mold is then heated and placed on a flexible, water-soluble substrate. After mold detachment, a dMN patch remains on the substrate. Droplet-born air blowing (DAB) applies a (A) polymer solution and (B) a drug solution to two plates. (C) The upper plate is lowered until the droplets meet, (D)then withdrawn a distance equal to the two dMN lengths of the lower and top plates. (E) Drying the polymer solutions results in a dMN patch on each plate. (F) In addition, fabrication at moderate temperatures (4–25 degrees Celsius) minimizes medication and polymer waste. dMN on an electrospun pillar array (DEPA) is a variant of DAB. (A) The flat plate is replaced with a columnar array covered in a fibrous layer. (B) A PDMS slab is then utilized to draw and stretch polymer formulation droplets, resulting in microneedles. (C) Finally, the movement of air dries off the elongated droplets to form dissolving microneedles.

Article Snippet: 7. , Nanopass (Microjet TM ) , Silicon microneedles , Influenza, Polio, Varicella-Zoster, cancers, Hepatitis B, and COVID-19.

Techniques: Polymer, Produced, Variant Assay, Formulation

Journal: Pharmaceutics

Article Title: Potential of Microneedle Systems for COVID-19 Vaccination: Current Trends and Challenges

doi: 10.3390/pharmaceutics14051066

Figure Lengend Snippet: Fabrication of novel dissolving MNAs with undercut microneedles. ( A ) Finished items according to each stage of the production plan outlined. The scale bar measures 10 mm. ( B – I ). Optical stereomicroscopy was used to verify the geometric quality of the produced MNAs. The scale bars are 250 m in length. ( B ) Three-dimensional direct laser writing was used to generate the master MNA. ( C ) A two-stage micromolding approach was used to generate a replica of the master MNA (elastomer molding combined with UV-curable micromolding). ( D ) Wells formed like microneedles in an MNA manufacturing mold. ( E ) Dissolving CMC/trehalose MNA in the final stage, including a multicomponent vaccine (OVA + Poly(I:C)). ( F ) A closer look at a single undercut microneedle on the 3D-printed master MNA (as in B). ( G ) Magnification of an individual undercut microneedle on a master MNA replica at higher magnification (as in C ). ( H ) Dissolving PVP/PVA microneedle tip filled with Alexa680-labeled OVA at the end. ( I ) A final dissolving CMC/trehalose microneedle tip filled with doxorubicin, a red-colored, chemotherapeutic, small-molecule medication, is shown. (Taken from ).

Article Snippet: 7. , Nanopass (Microjet TM ) , Silicon microneedles , Influenza, Polio, Varicella-Zoster, cancers, Hepatitis B, and COVID-19.

Techniques: Produced, Labeling

Journal: Pharmaceutics

Article Title: Potential of Microneedle Systems for COVID-19 Vaccination: Current Trends and Challenges

doi: 10.3390/pharmaceutics14051066

Figure Lengend Snippet: Companies developing microneedles for vaccine delivery.

Article Snippet: 7. , Nanopass (Microjet TM ) , Silicon microneedles , Influenza, Polio, Varicella-Zoster, cancers, Hepatitis B, and COVID-19.

Techniques: Vaccines

Journal: Scientific Reports

Article Title: Design and optimization of hollow microneedle spacing for three materials using finite element methods

doi: 10.1038/s41598-024-82564-8

Figure Lengend Snippet: Structural parameters of 9 groups of hollow microneedles.

Article Snippet: We conducted structural analysis and skin puncture studies of hollow microneedles using ANSYS for three materials: Hafnium Dioxide (HfO 2 ), Polyglycolic acid (PGA) and Polylactic acid (PLA).

Techniques:

Journal: Scientific Reports

Article Title: Design and optimization of hollow microneedle spacing for three materials using finite element methods

doi: 10.1038/s41598-024-82564-8

Figure Lengend Snippet: Deformation of hollow microneedles of three materials ( a ) HfO 2 material. ( b ) PGA material. ( c ) PLA material.

Article Snippet: We conducted structural analysis and skin puncture studies of hollow microneedles using ANSYS for three materials: Hafnium Dioxide (HfO 2 ), Polyglycolic acid (PGA) and Polylactic acid (PLA).

Techniques: