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

BACKGROUND AND OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Assessment of a 3050/3200 nm fiber laser system for ablative fractional laser treatments in dermatology.

BACKGROUND AND OBJECTIVES: Mid-infrared (IR) ablative fractional laser treatments are highly efficacious for improving the appearance of a variety of dermatological conditions such as photo-aged skin. However, articulated arms are necessary to transmit the mid-IR light to the skin, which restricts practicality and clinical use. Here, we have assessed and characterized a novel fiber laser-pumped difference frequency generation (DFG) system that generates ablative fractional lesions and compared it to clinically and commercially available thulium fiber, Erbium:YAG (Er:YAG), and CO2 lasers. MATERIALS AND METHODS: An investigational 20 W, 3050/3200 nm fiber laser pumped DFG system with a focused spot size of 91 µm was used to generate microscopic ablation arrays in ex vivo human skin. Several pulse energies (10-70 mJ) and pulse durations (2-14 ms) were applied and lesion dimensions were assessed histologically using nitro-blue tetrazolium chloride stain. Ablation depths and coagulative thermal damage zones were analyzed across three additional laser systems. RESULTS: The investigational DFG system-generated deep (>2 mm depth) and narrow (<100 µm diameter) ablative lesions surrounded by thermal coagulative zones of at least 20 µm thickness compared to 13, 40, and 320 µm by the Er:YAG, CO2 , and Thulium laser, respectively. CONCLUSION: The DFG system is a small footprint device that offers a flexible fiber delivery system for ablative fractional laser treatments, thereby overcoming the requirement of an articulated arm in current commercially available ablative lasers. The depth and width of the ablated microcolumns and the extent of surrounding coagulation can be controlled; this concept can be used to design new treatment procedures for specific indications. Clinical improvements and safety are not the subject of this study and need to be explored with in vivo clinical studies.

Ex vivo and animal study of the blue diode laser, Tm fiber laser, and their combination for laparoscopic partial nephrectomy.

BACKGROUND AND OBJECTIVES: To evaluate the feasibility of using a novel blue diode laser (blue laser), a thulium fiber laser (Tm laser), and their combination as a directed-energy surgical tool in laparoscopic partial nephrectomy (LPN). STUDY DESIGN/MATERIALS AND METHODS: The blue laser emitting at 442 nm, the Tm laser emitting at 1,940 nm wavelengths, and the combination of them were tested. First, cutting and coagulative abilities of the lasers were characterized ex vivo on porcine kidney in air and CO2 . Histological staining was performed to assess the efficiency of ablation and coagulation. Next, experimental LPN was performed on a porcine model at zero ischemia. Upper and lower segments of both kidneys were resected. Total operation time and resection time were measured; bleeding and carbonization were evaluated. RESULTS: Ex vivo data show that laser-induced ablation and coagulation processes do not differ substantially between CO2 and air environments. Histological analysis of ex vivo incisions demonstrates that the blue laser produced deep ablation with relatively narrow coagulation zone, whereas Tm laser was less efficient in terms of ablation but possessed excellent coagulative properties. Experimental LPN revealed that the blue laser provided fast cutting with minimal carbonization, whereas Tm laser induced slow cutting with strong carbonization. The combination of the blue and Tm lasers provided the most promising results demonstrating the highest resection rate, almost carbonization free resection surface and clinically acceptable hemostasis enabling LPN without the need for vessel clamping. CONCLUSIONS: The blue laser can be efficiently utilized in LPN. Furthermore, the combination of the blue and Tm lasers into a single modality may be beneficial for further development of successful laser-assisted LPN. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Distribution of thiolated mucoadhesive nanoparticles on intestinal mucosa.

It was the aim of the present study to evaluate and compare the distribution of thiolated mucoadhesive anionic poly(acrylic acid) (PAA) and cationic chitosan (CS) nanoparticles on intestinal mucosa. Modifications of these polymers were achieved by conjugation with cysteine (PAA-Cys) and 2-iminothiolane (CS-TBA). Nanoparticles (NP) were prepared by ionic gelation and labelled with the strong hydrophilic fluorescent dye Alexa Fluor 488 (AF 488) and hydrophobic fluorescein diacetate (FDA). Unmodified and modified CS and PAA NP were examined in vitro in terms of their mucoadhesive and mucus penetrating properties on the mucosa of rat small intestine. To investigate the transport of NP across the mucus layer, their diffusion behaviour through natural porcine intestinal mucus was studied through a new diffusion method developed by our group. Lyophilised particles displayed 526 µmol/g (CS) and 513 µmol/g (PAA) of free thiol groups and a zeta potential of 20 mV (CS) and -14 mV for PAA NP. Nanoparticle distribution on rat intestine suggested that mucoadhesion of thiolated NP is higher than the diffusion into the intestinal mucosa. Modified particles displayed more than a 6-fold increase in mucoadhesion compared to unmodified ones. The rank order with regard to mucoadhesion of all particles was: CS-TBA>PAA-Cys>CS>PAA, whereas CS-TBA showed 2-fold higher mucoadhesive properties compared to PAA-Cys NP. Diffusion through intestinal mucus was much higher for unmodified than for thiolated as well as for anionic compared to cationic particles. Overall, it was shown that thiolated particles of both anionic and cationic polymers have improved mucoadhesive properties and could be promising carriers for mucosal drug delivery.