Melatonin nanoemulgel for dermal applications: from formulation to in vivo imaging validation

Radiation-induced dermatitis is a prevalent side effect of radiotherapy worldwide. Conventional treatment strategies often fall short of achieving optimal therapeutic efficacy, primarily due to inadequate retention on the skin surface. This limitation has motivated research to find new nanotechnology-based treatment approaches to enhance therapeutic outcomes. Nanoformulations have emerged as a promising solution, offering improved therapeutic outcomes. In this study, authors investigated a combination therapy consisting of melatonin (MLT), vitamin E (VE), and N-acetyl cysteine (NAC). MLT is a naturally occurring hormone that has anti-inflammatory and antioxidant properties that may help treat cancer. It plays a crucial part in protecting healthy tissues by neutralizing various free radical scavengers generated by IR pro-oxidant enzymes that are triggered after exposure to IR. VE and NAC also depict radiomitigator properties. In the present study, nanoemulgel was formulated with Carbopol®940, which acts as a gelatinizing agent to facilitate effective delivery of these therapeutic agents at the target site. Pseudoternary phase diagrams were prepared to classify the area of nanoemulsion region. Globule size and zeta potential of optimized nanoemulsion formulation were observed to be 113.84 ± 0.648 nm and 34.2 ± 0.907 mV, respectively. Further, in vitro skin release studies showed 49.94 ± 3.01% cumulative release of MLT from nanoemulgel a time frame of 24 h. And the formulation followed Korsmeyer-Peppas model, which indicates that drug release is non-fickian. An FTIR analysis confirmed that MLT's characteristic peaks were preserved in the formulations, demonstrating that no interaction occurred between the constituents. The DSC thermogram of MLT nanoemulgel showed no sharp melting peak, suggesting molecular dispersion in oil phase. Additionally, gamma scintigraphy evaluation confirmed the formulation's long-term skin retention. In experimental results, nanoemulsion gel showed enhanced permeability and retention, making it a promising transporter for topical deliveries of bioactives for radiation-induced dermatitis prevention.