The physical mechanism relies on the creation of superficial microchannels via low-energy Ablative Fractional Laser (AFL). By precisely ablating tissue only down to the mid-epidermis, these settings generate micro-cavities that serve as physical reservoirs. This allows large antibody molecules (approximately 150 kDa) to bypass the skin's natural barrier and diffuse horizontally into the dermis for effective localized therapy.
By physically breaching the stratum corneum with mid-epidermal microchannels, this method circumvents the "500 Dalton rule," transforming the skin into a permeable matrix for the uniform distribution of large macromolecules.
Breaking the Barrier: The Physics of Ablation
Bypassing the 500 Dalton Rule
Intact skin is an incredibly effective barrier designed to keep foreign substances out. Under normal conditions, the "500 Dalton rule" applies, meaning molecules heavier than 500 Daltons cannot penetrate the skin.
Large molecular antibodies are significantly heavier, weighing in at approximately 150,000 Daltons (150 kDa).
To deliver these payloads, chemical enhancers are insufficient. You must use a physical method to disrupt the stratum corneum and create a direct pathway for entry.
Precision Depth Control
The success of this mechanism depends on the use of low-energy settings.
High-energy lasers drill deep, but for this specific application, the ablation is confined to the mid-epidermis.
This shallow depth creates the necessary opening without causing unnecessary trauma to the deeper dermal layers, striking a balance between permeability and tissue preservation.
The Micro-Channel as a Delivery System
Creating a Reservoir
The microchannels created by the laser do not merely act as funnels; they function as reservoirs.
Once the laser creates these micro-cavities, they can be filled with the antibody solution.
Because the stratum corneum has been ablated, the solution sits directly in contact with the viable epidermal tissue, protected within these tiny wells.
Achieving Uniform Distribution
The ultimate goal is not just entry, but distribution.
Once the antibodies are seated in the micro-channel reservoirs, they begin to diffuse horizontally.
This lateral movement is critical. It ensures that the medication spreads evenly throughout the dermis, resulting in a uniform distribution rather than a concentrated spot of medication at the injection site.
Understanding the Trade-offs
Depth vs. Efficacy
The limitation of this mechanism is defined by its low-energy nature. Because the channels only extend to the mid-epidermis, this method is strictly optimized for localized therapy.
It creates a path for large molecules to enter the skin, but it does not drive them deep into the bloodstream for systemic circulation immediately.
The mechanism relies entirely on passive diffusion from the reservoir, meaning the speed of delivery is dictated by the diffusion rate of the molecule, not active injection pressure.
Optimizing Delivery for Therapeutic Goals
The use of low-energy AFL represents a targeted approach to transdermal delivery. Here is how to view this mechanism in the context of your clinical objectives:
- If your primary focus is delivering macromolecules (>500 Daltons): You must utilize physical ablation to breach the stratum corneum, as chemical enhancers will fail with molecules of this mass (150 kDa).
- If your primary focus is uniform dermal coverage: You should rely on the horizontal diffusion capabilities of the micro-channel reservoirs to spread the therapy evenly across the treatment area.
By controlling the depth of ablation, you convert the skin’s protective barrier into a controlled delivery matrix.
Summary Table:
| Feature | Mechanism Detail | Impact on Delivery |
|---|---|---|
| Physical Breach | Ablation of Stratum Corneum | Bypasses the 500 Dalton rule for 150 kDa molecules |
| Energy Level | Low-energy AFL settings | Ensures mid-epidermal depth with minimal tissue trauma |
| Reservoir Effect | Micro-channel formation | Creates physical cavities to hold antibody solutions |
| Diffusion Mode | Horizontal lateral movement | Achieves uniform distribution throughout the dermis |
| Treatment Focus | Localized therapy | Optimized for targeted, even dermal coverage |
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References
- Rikke Louise Christensen, Uffe H. Olesen. Optical Imaging Visualizes a Homogeneous and Horizontal Band-Like Biodistribution of Large- and Small-Size Hydrophilic Compounds Delivered by Ablative Fractional Laser. DOI: 10.3390/pharmaceutics14081537
This article is also based on technical information from Belislaser Knowledge Base .
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