Characterization of skin blebs from intradermal jet injection: Ex-vivo studies

Simmons, Jonathan A.; Davis, Julie M.; Thomas, James B.; López, Juan Antonio; Blanc, Andrew Le; Allison, Haley; Slook, Haley; Lewis, Paul B.; Holtz, Joshua; Fisher, Paul D.; Broderick, Kate E.; Marston, Jeremy

doi:10.1016/j.jconrel.2019.06.032

Cited by 27 publications

(14 citation statements)

References 49 publications

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“…Unlike other studies that used glycerol for its viscosity increasing properties, we used it as diffusion enhancer due to its use in the pharmaceutical industry as a moisturizer. 16 As measured elsewhere, 46 both solutions behave as Newtonian fluids with measured constant viscosity g aqueous = 0.9 mPa.s and g glyc10% = 1.2 mPa.s. 33 The absorption was measured for both solutions in the spectral range of (300-1000) nm (UV-Visible Spectrophotometer UV-2600, Shimadzu).…”

Section: Liquid Solutionssupporting

confidence: 59%

“…To emulate real-life scenarios, and compensate for the fat removed, 5% agarose slabs were placed under the skin to still mimic the global skin stiffness. 29,46,48 The skin samples were carefully dried with a Kimwipe before each experiment to prevent solution running. On average, all samples were used for experimentation within 2 h after obtaining them from the abattoir.…”

Section: Ex Vivo Porcine Skinmentioning

confidence: 99%

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Delivery Strategies for Skin: Comparison of Nanoliter Jets, Needles and Topical Solutions

Bansal

Mitragotri

et al. 2019

Ann Biomed Eng

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Drug diffusion within the skin with a needle-free micro-jet injection (NFI) device was compared with two wellestablished delivery methods: topical application and solid needle injection. A permanent make-up (PMU) machine, normally used for dermal pigmentation, was utilized as a solid needle injection method. For NFIs a continuous wave (CW) laser diode was used to create a bubble inside a microfluidic device containing a light absorbing solution. Each method delivered two different solutions into ex vivo porcine skin. The first solution consisted of a red dye (direct red 81) and rhodamine B in water. The second solution was direct red 81 and rhodamine B in water and glycerol. We measured the diffusion depth, width and surface area of the solutions in all the injected skin samples. The NFI has a higher vertical dispersion velocity of 3 9 10 5 lm/s compared to topical (0.1 lm/s) and needle injection (53 lm/s). The limitations and advantages of each method are discussed, and we conclude that the micro-jet injector represents a fast and minimally invasive injection method, while the solid needle injector causes notable tissue damage. In contrast, the topical method had the slowest diffusion rate but causes no visible damage to the skin.

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Section: Liquid Solutionssupporting

confidence: 59%

Section: Ex Vivo Porcine Skinmentioning

confidence: 99%

Delivery Strategies for Skin: Comparison of Nanoliter Jets, Needles and Topical Solutions

Bansal

Mitragotri

et al. 2019

Ann Biomed Eng

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“…To investigate EPI parameters, skin-imitating media such as polyacrylamide gel and gelatin phantom have been used previously [10][11][12]. Moreover, EPI of ink followed by skin splitting and macroscopic evaluation, and histology imaging with hematoxylin and eosin (H&E) staining have also been used for optical imaging of EPI [10,11,[13][14][15]. Although transparent media provide a clear view of injected fluid patterns, skin phantoms are currently lacking the technical refinement to mimic the biological complexity of human skin [16].…”

Section: Introductionmentioning

confidence: 99%

Electronic Pneumatic Injection‐Assisted Dermal Drug Delivery Visualized by Ex Vivo Confocal Microscopy

et al. 2020

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Background and Objectives: Electronic pneumatic injection (EPI) is a technique for dermal drug delivery, which is increasingly being used in clinical practice. However, only few studies have been reported on cutaneous drug distribution and related clinical endpoints. We aimed to visualize the immediate cutaneous drug distribution, changes in skin architecture, and related clinical endpoint of EPI. Study Design/Materials and Methods: Acridine orange (AO) solution was administered to ex vivo porcine skin by EPI at pressure levels from 4 to 6 bar with a fixed injection volume of 50 µl and nozzle size of 200 µm. Immediate cutaneous distribution was visualized using ex vivo confocal microscopy (EVCM). Changes in skin architecture were visualized using both EVCM and hematoxylin and eosin-stained cryosections. Results: The defined immediate endpoint was a clinically visible papule formation on the skin. The pressure threshold to consistently induce a papule was 4 bar, achieving delivery of AO to the deep dermis (2319 µm axial and 5944 µm lateral distribution). Increasing the pressure level to 6 bar did not lead to significant differences in axial and lateral dispersion (P = 0.842, P = 0.905; respectively). A distinctively hemispherical distribution pattern was identified. Disruption of skin architecture occurred independently of pressure level, and consisted of subepidermal clefts, dermal vacuoles, and fragmented collagen. Conclusions: This is the first study to relate a reproducible clinical endpoint to EPI-assisted immediate drug delivery using EVCM. An EPI-induced skin papule indicates dermal drug delivery throughout all layers of the dermis, independent of pressure level settings. Lasers Surg. Med.

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“…Besides chemical enhancement methods, the application of several physical technologies (e.g., IP, ultrasound, microneedles, electroporation, a pyro-jet injector, and thermal ablation) has garnered significant attention as a means to facilitate the skin permeation of biological macromolecular drugs [ 42 , 43 , 44 , 45 , 46 , 47 ]. These methods use different types of physical forces that either disrupt or bypass skin barriers.…”

Section: Challenges Of the Noninvasive Transdermal Delivery Of Biolog...mentioning

confidence: 99%

Iontophoresis of Biological Macromolecular Drugs

2022

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Over the last few decades, biological macromolecular drugs (e.g., peptides, proteins, and nucleic acids) have become a significant therapeutic modality for the treatment of various diseases. These drugs are considered superior to small-molecule drugs because of their high specificity and favorable safety profiles. However, such drugs are limited by their low oral bioavailability and short half-lives. Biological macromolecular drugs are typically administrated via invasive methods, e.g., intravenous or subcutaneous injections, which can be painful and induce needle phobia. Noninvasive transdermal delivery is an alternative administration route for the local and systemic delivery of biological macromolecular drugs. However, a challenge with the noninvasive transdermal delivery of biological macromolecular drugs is the outermost layer of the skin, known as the stratum corneum, which is a physical barrier that restricts the entry of extraneous macromolecules. Iontophoresis (IP) relies on the application of a low level of electricity for transdermal drug delivery, in order to facilitate the skin permeation of hydrophilic and charged molecules. The IP of several biological macromolecular drugs has recently been investigated. Herein, we review the IP-mediated noninvasive transdermal delivery of biological macromolecular drugs, their routes of skin permeation, their underlying mechanisms, and their advance applications.

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Characterization of skin blebs from intradermal jet injection: Ex-vivo studies

Cited by 27 publications

References 49 publications

Delivery Strategies for Skin: Comparison of Nanoliter Jets, Needles and Topical Solutions

Delivery Strategies for Skin: Comparison of Nanoliter Jets, Needles and Topical Solutions

Electronic Pneumatic Injection‐Assisted Dermal Drug Delivery Visualized by Ex Vivo Confocal Microscopy

Iontophoresis of Biological Macromolecular Drugs

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