Aestheticizing the Self-Stabilized Pickering Emulsion of Capecitabine: Harnessing Polysarcosine Nanoparticles for Exquisite Targeted Therapy of Squamous Cell Carcinoma; An Elaborate In Vivo and In Vitro Evaluation

Abstract

This study focuses on the formulation, optimization, and characterization of a water-in-oil (W/O) Pickering emulsion (PE) containing capecitabine (CAP), which is self-stabilized using polysarcosine (Psar) nanoparticles (NPs), to create a topical treatment for squamous cell carcinoma (SCC). The polysarcosine nanoparticles (Psar-NPs) were prepared using the Box-Behnken design and the nanoprecipitation technique. Among 17 different formulations, the F16 formulation was identified as optimal. The particle size, zeta potential, and drug entrapment efficiency of the optimized Psar-NPs were 224 ± 4.4 nm, 21.90 ± 0.90 mV, and 74.30 ± 2.1%, respectively.

The gel incorporating CAP-PsarNPs-PE provided a slow and sustained release of the drug, showing 82.27 ± 5.23% release over 24 h, in comparison to CAP-PsarNPs-PE alone, which released 77.41 ± 4.1% in just 12 h. Stability tests over 90 days confirmed that the emulsion remained uniformly stable, with no signs of droplet coalescence. A series of in vitro tests, including SRB assay, cell cycle analysis, apoptosis detection, ROS estimation, MMP assessment, DNA fragmentation, and scratch assays, demonstrated that CAP-PsarNPs-PE effectively controlled cancer cell growth in NCL-H226 carcinoma cells. Since the low viscosity of the emulsion made it less effective for retention on the skin, it was incorporated into a gel.

The texture profile of the CAP-PsarNPs-PE gel showed enhanced mechanical properties, making it more suitable for topical application. In vivo skin irritation studies on rats confirmed that the gel was non-irritating and safe for topical use, with no significant histopathological changes observed. In conclusion, the CAP-PsarNPs-PE and its gel formulation, offer a promising and efficient treatment option for squamous cell carcinoma, providing targeted, sustained drug delivery for improved therapeutic outcomes.