Linking interfacial behavior to thermo-diffusive cisplatin release in biopolymeric nanogels

Cisplatin-loaded biopolymeric nanogels are promising carriers for sustained anticancer drug delivery; however, establishing physically interpretable links between formulation structure, transport behavior, and temperature-dependent release remains challenging. Here, mucilage-alginate-coated chitosan (MACC) nanogels were developed and evaluated using an integrated framework combining empirical kinetic analysis, mechanistic thermo-diffusive modeling, and complementary interfacial characterization. Basil seed mucilage was incorporated as a hydrophilic shell modifier to tune nanogel physicochemical behavior and release performance. The optimized MACC₂ formulation showed stable core-shell morphology, an average particle size of 75 ± 12 nm, and an encapsulation efficiency of 46.85%. In vitro assays demonstrated high compatibility with normal fibroblast cells and dose-dependent inhibition of MCF-7 breast cancer cells, supporting controlled cisplatin delivery. Drug release in PBS (pH 7.4) followed a biphasic profile with an initial burst stage and a sustained diffusion-dominated regime. Temperature-dependent studies at 35-39 °C showed accelerated release, with effective diffusion coefficients increasing from 2.0 × 10^-21 to 3.6 × 10^-21 m² s^-1, while Arrhenius analysis supported thermally activated transport within the hydrated polymeric matrix. Empirical kinetic modeling further indicated predominantly diffusion-controlled release with secondary polymer-relaxation contributions. Air-water interfacial tensiometry showed reduced interfacial activity for mucilage-containing nanogels, consistent with increased aqueous affinity and formulation-dependent physicochemical behavior. These measurements were interpreted as complementary descriptors rather than direct evidence of hydration or bulk diffusion. Overall, this integrated empirical-mechanistic-interfacial framework provides a physically interpretable approach for analyzing thermo-diffusive cisplatin transport in hydrated biopolymeric nanogels.