Full-surface laser ablation has been shown to efficiently disrupt stratum corneum and facilitate transcutaneous drug delivery, but it is frequently associated with skin damage that hampers its clinic use. We show here that a safer ablative fractional laser (AFL) can sufficiently deliver not only patch-coated hydrophilic drugs but also protein vaccines. AFL treatment generated an array of self renewable microchannels (MCs) in the skin surface, providing free paths for drug and vaccine delivery into the dermis while sustains integrity of the skin by quick healing of the MCs. AFL was superior to tape stripping in transcutaneous drug and vaccine delivery as a much higher amount of sulforhodamine B (SRB), methylene blue (MB) or a model vaccine ovalbumin (OVA) was recovered from AFL-treated skin than tape stripping-treated skin or control skin after patch application. Following entry into the MCs, the drugs or OVA diffused quickly to the entire dermal tissue via the lateral surface of conical-shaped MCs. In contrast, a majority of the drugs and OVA remained on the skin surface, unable to penetrate into the dermal tissue in untreated control skin or tape stripping-treated skin. Strikingly, OVA delivered through the MCs was efficiently taken up by epidermal Langerhans cells and dermal dendritic cells in the vicinity of the MCs or transported to the draining lymph nodes, leading to a robust immune response, in sharp contrast to a weak, though significant, immune response elicited in tape stripping group or a basal immune response in control groups. These data support strongly that AFL is safe and sufficient for transcutaneous delivery of drugs and vaccines.

The pathophysiology of acne vulgaris depends on active sebaceous glands, implying that selective destruction of sebaceous glands could be an effective treatment. We hypothesized that light-absorbing microparticles could be delivered into sebaceous glands, enabling local injury by optical pulses. A suspension of topically applied gold-coated silica microparticles exhibiting plasmon resonance with strong absorption at 800 nm was delivered into human pre-auricular and swine sebaceous glands in vivo, using mechanical vibration. After exposure to 10–50 J cm−2, 30 milliseconds, 800 nm diode laser pulses, microscopy revealed preferential thermal injury to sebaceous follicles and glands, consistent with predictions from a computational model. Inflammation was mild; gold particles were not retained in swine skin 1 month after treatment, and uptake in other organs was negligible. Two independent prospective randomized controlled clinical trials were performed for treatment of moderate-to-severe facial acne, using unblinded and blinded assessments of disease severity. Each trial showed clinically and statistically significant improvement of inflammatory acne following three treatments given 1–2 weeks apart. In Trial 2, inflammatory lesions were significantly reduced at 12 weeks (P=0.015) and 16 weeks (P=0.04) compared with sham treatments. Optical microparticles enable selective photothermolysis of sebaceous glands. This appears to be a well-tolerated, effective treatment for acne vulgaris.

Background Lasers and intense pulsed light sources (IPLS) are proposed for the treatment of many pigmentary disorders. They are sometimes considered as magic tools able to remove any type of lesions. Although being the best option for several hyperpigmented lesions, they can also worsen some conditions and have potential side‐effects. Objective The aim of this review was to give evidence‐based recommendations for the use of lasers and IPLS in the treatment of hyperpigmented lesions. Methods These recommendations were produced for the European Society of Laser Dermatology by a consensus panel made up of experts in the field of pigment laser surgery. Recommendations on the use of lasers and light treatments were made based on the quality of evidence for efficacy, safety, tolerability, cosmetic outcome, patient satisfaction/preference and, where appropriate, on the experts' opinion. Results Lasers and IPLS are very effective for treating many hyperpigmented lesions such as lentigos, dermal hypermelanocytosis or heavy metal depositions. In the other hand, they have to be considered with great caution for other disorders, such as café au lait macules, melasma or postinflammatory hyperpigmentation. After making the correct diagnosis, if lasers or IPLS are indicated, the optimal wavelengths and parameters will be chosen taking into account the skin phototype, origin and depth of the target pigments. Conclusion Although potentially very effective, lasers and IPLS cannot be proposed for all types of hyperpigmented lesions. In all cases, precise recognition of the disorder is mandatory for choosing between these devices and other therapeutic approaches.

Skin vaccination has gained increasing attention in the last two decades due to its improved potency compared to intramuscular vaccination. Yet, the technical difficulty and frequent local reactions hamper its broad application in the clinic. In the current study, micro-fractional epidermal powder delivery (EPD) is developed to facilitate skin vaccination and minimize local adverse effects. EPD is based on ablative fractional laser or microneedle treatment of the skin to generate microchannel (MC) arrays in the epidermis followed by topical application of powder drug/vaccine-coated array patches to deliver drug/vaccine into the skin. The novel EPD delivered more than 80% sulforhodamine b (SRB) and model antigen ovalbumin (OVA) into murine, swine, and human skin within 1 hour. EPD of OVA induced anti-OVA antibody titer at a level comparable to intradermal (ID) injection and was much more efficient than tape stripping in both delivery efficiency and immune responses. Strikingly, the micro-fractional delivery significantly reduced local side effects of LPS/CpG adjuvant and BCG vaccine, leading to complete skin recovery. In contrast, ID injection induced severe local reactions that persisted for weeks. While reducing local reactogenicity, EPD of OVA/LPS/CpG and BCG vaccine generated a comparable humoral immune response to ID injection. EPD of vaccinia virus encoding OVA induced significantly higher and long-lasting interferon γ-secreting CD8+ T cells than ID injection. In conclusion, EPD represents a promising technology for needle-free, painless skin vaccination with reduced local reactogenicity and improved immunogenicity.

The need for patient-specific photodynamic therapy (PDT) in dermatologic and oncologic applications has triggered several studies that explore the utility of surrogate parameters as predictive reporters of treatment outcome. Although photosensitizer (PS) fluorescence, a widely used parameter, can be viewed as emission from several fluorescent states of the PS (e.g., minimally aggregated and monomeric), we suggest that singlet oxygen luminescence (SOL) indicates only the active PS component responsible for the PDT. Here, the ability of discrete PS fluorescence-based metrics (absolute and percent PS photobleaching and PS re-accumulation post-PDT) to predict the clinical phototoxic response (erythema) resulting from 5-aminolevulinic acid PDT was compared with discrete SOL (DSOL)-based metrics (DSOL counts pre-PDT and change in DSOL counts pre/post-PDT) in healthy human skin. Receiver operating characteristic curve (ROC) analyses demonstrated that absolute fluorescence photobleaching metric (AFPM) exhibited the highest area under the curve (AUC) of all tested parameters, including DSOL based metrics. The combination of dose-metrics did not yield better AUC than AFPM alone. Although sophisticated real-time SOL measurements may improve the clinical utility of SOL-based dosimetry, discrete PS fluorescence-based metrics are easy to implement, and our results suggest that AFPM may sufficiently predict the PDT outcomes and identify treatment nonresponders with high specificity in clinical contexts.

The current study has demonstrated rapid fibrin plug formation after ablative fractional laser procedures. It was shown that the passage through laser created pathways is critically time dependent for in vivo exposures. In contrast, ex vivo exposures do not exhibit such time dependent passage capacity. In particular, drug, substance, and cell delivery studies for ablative fractional laser treatments should take early fibrin plug formation into consideration and further investigate the impact on transdermal delivery.

The tunable laser system provides a useful research tool to investigate specific laser parameters such as wavelength on lesion shape, ablation depth and thermal tissue damage. It also allows for customization of the characteristics of laser lesions and therefore facilitates the selection of suitable laser parameters for optimized fractional laser treatments. Lasers Surg. Med. 50:961-972, 2018.© 2018 Wiley Periodicals, Inc.

Irradiation using an AFR laser may induce the expression of Wnt5a, CYR61, and HSP90 in human skin during the early remodeling phases, suggesting that the induction of proteins may be the preceding event that is associated with the clinical effects of laser treatment.