Dynamic OCT imaging objectively measures inflammatory response due to MAP insertion, in-vivo and in real-time.
Research efforts on MAPs are at an all-time high. It is important to understand skin reactions during and after MAP applications, and further gain insights on MAP changes themselves as well. Questions that may arise are:
- What are pertinent MAP geometric parameters?
- What structural changes can be observed between the MAP and skin interface?
- What vascular changes take place?
- What are the implications?
Measuring geometric parameters such as microneedle depth of penetration, deformation, swelling and dissolution have been well described in the literature (Fig.1) [1-3]. We report on two aspects that describe changes in the skin and in more detail outline the dramatic difference of vascular expression upon MAP insertion and removal.
The MAP / Skin Interface
Using “super swelling” hydrogel-forming MAPs, basic insertion tests were carried out. VivoSight OCT imaging visualizes and quantifies areas of interest (Fig.2):
Visualizing the insertion behavior of MAPs and its structural impact on skin provides a good foundation to investigate the ensuing inflammatory reaction.
Strong MAP Impact on Vascular Expression
After MAP insertion, an immediate vascular response is set in motion. The measurable increase in vascular expression is a function of a multitude of parameters such as needle depth, needle spacing, subject predisposition, repeat applications etc…
Understanding these relationships is paramount, as they have a strong impact on the pharmacokinetic availability of active substances over time. Dynamic OCT is useful to analyze the evolving interdependencies, and we present here imaging and measurements of vascular changes due to MAP insertion:
1: Baseline characterization of targeted skin area before MAP insertion:
Bottom: frame “side’ view of vertical skin slice with visible epidermis and red highlighted blood vessels.
Top right: en-face “top down” view of horizontal section at level of selectable depth (thin green line in bottom image). The beginning of the superficial vascular plexus comes into view.
Top left: 3D representation of vascular network at level of horizontal slice.
Global vascular metrics are automatically calculated to quantify the vascular network:
- Superficial vascular plexus depth: 430 μm
- Modal vessel diameter: 36 μm
- Vessel density: 9%
2: Skin area immediately after MAP removal:
A hydrogel-forming MAP was applied to skin and held in place for 34 minutes with Tegaderm.
Vascular expression is more pronounced than without MAP and exhibits significantly different parameters:
- Superficial vascular plexus depth: 241 μm
- Modal vessel diameter: 57 μm
- Vessel density: 40%
(Horizontal cuts are taken at same depth for both cases 1 and 2)
Take Home Message
Drug uptake is impacted by the skin vascular microcirculation and increased influx of immune cells from other parts of the body could possibly enhance an overall immune response to a vaccine deposited in the viable skin layer. Differences in vascular perfusion can be accurately measured in real-time and in-vivo. Quantification provides for objective comparison of vascular profiles and allows for more effective research on:
- How do different MAP designs and usage protocols change vascular perfusion?
- How does vascular perfusion impact the specific purpose of MAPs?
- What are the objective vascular recovery kinetics back to baseline?
Investigating these and related topics will accelerate MAP development and market introduction.
References:
- 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
- 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
- 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
About Professor Ryan Donnelly, PhD:
https://pure.qub.ac.uk/en/persons/ryan-donnelly
