VivoSight Imaging and Measurements for Microneedle Optimization

Visualize micro-channel creation and insertion depth. Monitor the time course of needle degradation or swelling and skin and vascular changes at the insertion site

 

VivoSight provides unique microneedle (MN) imaging and measurements to optimize:

  • Performance of MN-based drug delivery
  • MN insertion and retention consistency
  • Long-term safety of repeated MN applications
  • Development of standards for MN design, manufacturing and quality control

 VivoSight real-time in-vivo imaging of MNs

VivoSight Dx capabilities to advance your MN development include:

  • VivoSight Dx capabilities to advance your MN development include: In-vivo imaging of microneedles in real time
  • Measure microneedle dimensions, penetration depth, dissolution and swelling
  • Measure inflammatory response via vascular changes
  • Understand morphology of device created skin defects
  • Measure kinetics of pore closure and skin recovery
  • Verify reproducibility, consistency of results
VivoSight OCT image with vascular overlay. Microneedle penetrates 800 μm deep
VivoSight image with vascular overlay. Microneedle penetrates 800 μm deep [2]

“VivoSight OCT is essential for our microneedle research and for the development of related devices and applications. The ability to visualize polymeric microneedles in-vivo allows for measurement of the exact depth of penetration. Moreover, OCT allows us to monitor swelling and dissolution kinetics of biodegradable needles. It is an indispensable tool to advance and optimize Microneedle Array Patch (MAP) research and product development”. [1, 3]

Ryan F. Donnelly, PhD, School of Pharmacy, Queen’s University Belfast, UK

In-Vivo Structural Analysis of Microneedle Array Patches (MAPs)

VivoSight pixel resolution of 4.4 μm can identify the details of most microneedle arrays

Geometry of Microneedles with VivoSight OCT
Image stacks can contain up to 500 frames, which is sufficient detail to capture the geometries of most MAPs

The patch in this image has a 400 μm thick substrate with MN dimensions of 500 μm long and 300 μm in diameter

Varying air gaps in microneedles. Imaged with VivoSight OCT
Magnified in-vivo view of MAP. Note varying air gap and needle penetration

Polymer MAPs reflect light differently than skin allowing them to be identified in-vivo

MAP measures via OCT:

  • Needle dimensions
  • Needle penetration depth
  • Pore diameter
  • Air gap
  • Substrate thickness
  • Dissolution and swelling behavior
Varying air gaps in microneedles. Imaged with VivoSight OCT

Relevance of MAP measurements [3]

VivoSight 6 mm x 6 mm field of view encompasses a large portion of an array

VivoSight image stack can be viewed frame by frame to focus on areas of interest for measurements like consistent penetration depth

VivoSight allows you to monitor and measure needle length and insertion depth over time

Microneedle Penetration chat VivoSight OCT

VivoSight allows you to monitor and measure pore size, swelling and dissolution over time

Proportion of needle affected increases linearly with time
OCT visualizes change of polymer state as it hydrates (turns from grey to black)
Pore size shown to slightly reduce with time as the needle dissolves
Pore size shown to slightly reduce with time as the needle dissolves

Real-time, in-vivo time course of structural change

MAP in-vivo dynamics can impact performance and inform patch design

0 minutes after insertion
4.5 minutes
11 minutes
19 minutes
23 minutes
34 minutes

Measure and Monitor Tissue Response After MAP Removal

VivoSight produces 3-D surface images to monitor hole closure after MAP removal

Microneedle Patch imaged with OCT Top Down view
45 min after MAP removal
21 hours after MAP removal

Hole closure time can inform safety and cosmesis

Immediately after MAP removal
21 hrs after MAP removal

Tissue in 3D, 21 hrs after MAP removal

In-Vivo Vascular Analysis

VivoSight detects blood flow producing 3-D images and vessel measurements

Vascular changes in response to MAP application can be visualized and measured

MAP impact on vascular changes can be monitored over time

Polymer MAP with no therapeutic compound:

 

  • Initial rapid and dramatic response
  • Response subsides over first 20-35 minutes
  • Polymer material, needle geometry, array configuration, needle drug load, may all affect response time course

VivoSight can monitor the inflammatory response over time after MAP removal

Skin blood flow returns to normal after about 25 min
Modal vessel diameter decreasing by about 30%
Plexus depth increase to normal levels

Summary 

VivoSight OCT: visualize, measure and monitor in-vivo to optimize MAPs

  • Penetration depth
  • Swelling
  • Dissolution
  • Inflammatory response
  • Vascular plexus depth
  • Vessel diameter
  • Vascular density
  • Skin recovery
  • Geometry optimization
  • Material optimization
  • Local drug response

References:

1. R.F. Donnelly et al. Optical coherence tomography is a valuable tool in the study of the effects of microneedle geometry on skin penetration characteristics and in-skin dissolution. Journal of Controlled Release 147 (2010) 333–341

2. S. Sharma, et al., Rapid, low cost prototyping of transdermal devices for personal healthcare monitoring, Sensing and Bio-Sensing Research (2016), http://dx.doi.org/10.1016/j.sbsr.2016.10.004

3. R.F. Donnelly et al. Evaluation of the clinical impact of repeat application of hydrogel-forming microneedle array patches. Drug Delivery and Translational Research (Feb 2020). https://doi.org/10.1007/s13346-020-00727-2

4. E. Kim et al., Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development, EBioMedicine (2020), https://doi.org/10.1016/j.ebiom.2020.102743

5. M. R. Prausnitz, Engineering Microneedle patches for vaccination and drug delivery to skin. Annu. Rev. Chem. Biomol. 8, 177–200 (2017).

6. J. W. Lee, J. H. Park, M. R. Prausnitz, Dissolving microneedles for transdermal drug delivery. Biomaterials 29, 2113–2124 (2008).

7. Banzhaf CA, Wind BS, Mogensen M, Meesters AA, Paasch U, Wolkerstorfer A, Haedersdal M. Spatiotemporal Closure of Fractional Laser-Ablated Channels Imaged by Optical Coherence Tomography and Reflectance Confocal Microscopy, Lasers Surg Med. 2016 Feb;48(2):157-65