A Parametric COMSOL Study of Drug–Polymer Interactions and Release Dynamics in PLGA Electrospun Carriers

Local chemotherapy using biodegradable polymeric implants offers a promising strategy for increasing intratumoral drug exposure while potentially reducing systemic drug exposure. In this study, we developed a two-dimensional axisymmetric computational model in COMSOL Multiphysics to investigate doxorubicin release from an electrospun poly(lactic-co-glycolic acid) (PLGA) pad implanted on the surface of a solid tumor. The model couples drug diffusion, reversible binding, cellular internalization, intracellular degradation, polymer degradation, porosity evolution, and morphology-dependent transport properties. Drug release from the PLGA matrix was described using a mechanistic framework accounting for dissolution, reprecipitation, autocatalytic degradation, and erosion-induced changes in effective diffusivity. Tumor transport included extracellular diffusion, vascular clearance, reversible binding, and intracellular uptake. We evaluated the influence of key design and transport parameters, including pad size, porosity, drug hydrophobicity, diffusion coefficients, binding kinetics, and mass-transfer characteristics, using a One-Factor-at-a-Time (OFAT) sensitivity analysis. The simulations predicted a characteristic biphasic release profile consisting of an initial burst phase followed by long-term sustained release extending up to ۲۰۰ days. Increased pad porosity, larger implant dimensions, enhanced interfacial mass transfer, and stronger cellular binding increased intracellular drug accumulation and PharmacoKinetic Cellular exposure (PKC) metrics. Polymer degradation progressively increased porosity and effective diffusivity, leading to changes in release behavior over time as porosity and effective diffusivity evolved. The model also demonstrated that intracellular kinetic parameters significantly affect intracellular exposure metrics despite limited influence on extracellular drug concentrations. Overall, the proposed framework provides a mechanistic tool for investigating the interplay between implant design, polymer morphology, and tumor transport processes, supporting the investigation of electrospun PLGA-based local chemotherapy systems.

کلیدواژه ها:

Drug delivery ، Mathematical simulation ، electrospun pad ، Tumor ، COMSOL