Novel 40 µm spot size 3050/3200 nm DFG laser versus CO₂ laser for laser-assisted drug delivery

The use of ablative fractional lasers to enhance the delivery of topical drugs through the skin is known as laser-assisted drug delivery. Here, we compare a novel 3050/3200 nm difference frequency generation (DFG) fiber laser (spot size: 40 µm) to a commercially used CO₂ laser (spot size: 120 µm). The objective is to determine whether differences in spot size and coagulation zone (CZ) thickness influence drug uptake.

Fractional ablation was performed on ex-vivo human abdominal skin with the DFG (5 mJ) and CO₂ (12 mJ) lasers to generate 680 µm deep lesions. To evaluate drug delivery, 30 kDa encapsulated fluorescent dye was topically applied to the skin and histologically analyzed at skin depths of 100, 140, 200, 400, and 600 µm. Additionally, transcutaneous permeation of encapsulated and 350 Da nonencapsulated dye was assessed using Franz Cells.

The DFG laser generated smaller channels (diameter: 56.5 µm) with thinner CZs (thickness: 22.4 µm) than the CO₂ laser (diameter: 75.9 µm, thickness: 66.8 µm). The DFG laser treated group exhibited significantly higher encapsulated dye total fluorescence intensities after 3 h compared to the CO₂ laser treated group across all skin depths (p < 0.001). Permeation of nonencapsulated dye was also higher in the DFG laser treated group vs the CO₂ laser treated group after 48 h (p < 0.0001), while encapsulated dye was not detected in any group.

The DFG laser treated skin exhibited significantly higher total fluorescence uptake compared to the CO₂ laser. Additionally, the smaller spot size and thinner CZ of the DFG laser could result in faster wound healing and reduced adverse effects while delivering similar or greater amount of topically applied drugs.