ABSTRACT
OBJECTIVES: Although transdermal drug delivery system (TDDS) has been successfully used for delivering small molecules, its application in the delivery of diagnostic antibodies has been limited due to their large size. In this study, we aim to obtain a broad insight in the dynamics of TRITC-conjugated Goat Anti-Mouse IgG (T-IgG) uptake in fractional Er:YAG laser pretreated skin and provide a new technical option for detecting lupus erythematosus (LE) in mice. METHODS: The skins of SD and MRL/lpr mice were treated by fractional Er:YAG laser followed by external application of T-IgG. The classic Franz diffusion method was used to observe the effects of different fractional fluences, densities and antibody concentrations on transdermal delivery of T-IgG at different time points (2, 4, 6, 8, 20, and 24 hours). Frozen tissue sections and confocal microscopy were used to observe the distribution of T-IgG on the sagittal and coronal planes of murine skin. RESULTS: Increased laser fluence (12.5 J/cm2 to 37.5 J/cm2 ) within 24 hours resulted in the obvious increase in transdermal amounts of T-IgG during the early stage (before 8 hours). However, increasing laser density (100 pores/cm2 to 200 pores/cm2 ) produced a significant increase in T-IgG permeation during the late stage (20 and 24 hours). Unlike fluence and density, increase in T-IgG loading concentration (0.5 to 2 µg/µl) led to continuous increase in the whole process of transdermal delivery. T-IgG appeared in the micro-pores of SD mice skin within 4 hours after treatment in vivo. After 24 hours, it was observed in the skin. In MRL/lpr mice, positive lupus band testing (LBT) could be found on the skin lesion after laser and T-IgG external application. CONCLUSIONS: Fractional Er:YAG laser can help antibodies (150 kDa) to implement effective and controllable transdermal delivery. LBT can be achieved in MRL/lpr mice using TDDS in vivo, which may contribute to the minimally invasive diagnosis of LE. Lasers Surg. Med. 51:268-277, 2019. © 2018 Wiley Periodicals, Inc.
Subject(s)
Immunoglobulin G/administration & dosage , Lasers, Solid-State , Lupus Erythematosus, Cutaneous/diagnosis , Administration, Cutaneous , Animals , Disease Models, Animal , Drug Delivery Systems , Fluorescent Antibody Technique , Mice , Mice, Inbred MRL lpr , Rats, Sprague-DawleyABSTRACT
For superficial skin tumors (SST) with high incidence, surgery and systemic therapy are relatively invasive and possible to cause severe side effect, respectively. Yet, topical therapy is confronted with the limited transdermal capacity because of the stratum corneum barrier layer of skin. Therefore, it is crucial to develop a highly effective and minimally invasive alternative transdermal approach for treating SST. Here, we developed gold nanocage (AuNC)- and chemotherapeutic drug doxorubicin (DOX)-loaded hyaluronic acid dissolving microneedle (MN) arrays. The loaded AuNCs are not only reinforcers to enhance the mechanical strength of the MNs, but also effective agents for photothermal therapy to obtain effective transdermal therapy for SST. The resultant MNs can effectively penetrate the skin, dissolve in the skin and release cargoes within the tumor site. Photothermal effect of AuNCs initiated by near-infrared laser irradiation combined with the chemotherapy effect of DOX destroyed tumors synergistically. Moreover, we verified the potent antitumor effects of the DOX/AuNC-loaded MNs after four administrations to SST-bearing mice without obvious side effects. Therefore, the drug/AuNC-loaded dissolving MN system provides a promising platform for effective, safe, minimally invasive combined treatment of SST.
