Box–Behnken design–based optimization of Imatinib mesylate PLGA nanoparticle-loaded gel for topical management of Dermatofibrosarcoma Protuberans

Dermatofibrosarcoma Protuberans (DFSP) is a rare, locally aggressive cutaneous sarcoma. Its development is related to the specific PDGFB-COL1A1 fusion gene, which leads to constitutive signaling through tyrosine kinase. While Imatinib Mesylate is known to be effective in targeting this signaling pathway, systemic therapy may cause significant systemic exposure and safety concerns. Thus, in this study, we present a Box–Behnken Design-optimized Imatinib Mesylate PLGA nanogel as a localized topical system for DFSP management. In the experiment, Imatinib-loaded PLGA nanoparticles were prepared through solvent evaporation and optimized using the Box–Behnken design by varying concentrations of PLGA, PVA, and the volume of the organic phase. The optimized nanoparticles were incorporated into Carbopol 940 gel to form a novel nanogel. Physicochemical properties of the nanogel were determined, followed by in vitro release, ex vivo permeation, skin retention, and stability studies. The optimized nanoparticles showed approximately 255 nm particle size, PDI < 0.2, and > 75% entrapment efficiency. The nanogel was characterized by suitable pH, viscosity, spreadability, and drug content. It showed improved drug release, permeation, and much higher skin retention compared with conventional gel. Stability testing showed that physicochemical characteristics were maintained during storage. Addition of nanoparticles contributed to better dermal delivery, while the gel matrix ensured prolonged local residence. Higher skin retention suggests localized drug deposition and may be important for DFSP management.