In Vivo Percutaneous Penetration of Dye into IgWAT and IBAT Using Dissolving Microneedle and Iontophoresis

Abstract

Abstract Objectives Browning subcutaneous (subQ) white adipose tissue (WAT) or activating brown adipose tissue (BAT) is a promising approach for combating obesity and its comorbidities. Transdermal delivery of browning compounds efficiently to subQ WAT or BAT via microneedle (MN) and iontophoresis, if successful, will represent a new paradigm for treating obesity and its related metabolic disorders in a much more effective, comfortable, easy and safe regimen. The purpose of this study was to investigate the application of dissolving MN in combination with iontophoresis on the skin of mice for transdermal delivery of dye to inguinal WAT (IgWAT) or interscapular BAT (IBAT). Methods Dissolving MN was fabricated using poly (lactic-co-glycolic acid) (PLGA). C57BL/6 J mice received the following 4 treatments: 1. Control (no MN or iontophoresis), 2. MN alone, 3. Iontophoresis alone and 4. MN plus iontophoresis. The 1,1′-dioctadecyl-3,3,3′,3′- tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate salt (DID) dye was loaded into the MN. Treatments were applied on the skin above IgWAT and IBAT of mice. After 24 hours, dye distribution in the body was imaged using an in vivo imaging system (IVIS). After sacrifice, the IgWAT, IBAT, liver, kidneys, lung, and heart were dissected for further analysis. The IVIS imaging system in this study was used to analyze all fluorescence data. Results The average fluorescent intensity from the treated IgWAT and IBAT area of mice was 2.04 102 and 4.16 102 fold higher in MN plus iontophoresis than MN or iontophoresis alone, respectively. The same pattern was also seen in dissected IgWAT and IBAT with 2.73 102 and 3.57 102 fold higher average fluorescent intensity in MN plus iontophoresis treatment than MN or iontophoresis alone. In summary, mice treated with MN plus iontophoresis had higher fluorescent signals in IgWAT and IBAT than the other groups of mice. No fluorescent signals were detected in other collected organs. Conclusions MN in combination with iontophoresis can synergistically enhance transdermal delivery of dye or browning agents to IgWAT and IBAT mice, which might combat obesity via enhancing subQ WAT browning or increasing BAT activity. Funding Sources NIH 1R15AT010395 and AHA 19AIREA34480011.