Compartmental Modeling for Nanoparticle Drug Delivery Optimization How NovaMechanics developed a compartmental modelling platform for optimizing nanoparticle drug delivery efficiency through kinetic simulation and sensitivity analysis of PEG-coated gold nanoparticles. RSC Sustainability • 2025 Optimizing Nanoparticle Drug Delivery Nanoparticle-based drug delivery systems face a fundamental challenge: most administered NPs end up in off-target organs rather than the intended tissue. Only a fraction reaches the target cells, and even fewer are internalized. Optimizing delivery efficiency requires understanding the kinetic processes governing NP distribution, degradation, and excretion — and identifying which parameters most influence therapeutic outcome. 5 Kinetic compartments modelled 0.88 SODI achieved for PEG-Au NPs 10.5 nm PEG-coated Au NP diameter Five-Compartment Kinetic Model Developed a compartmental model with five physiological compartments: administration site, target cell vicinity, cell interior, off-target sites, and excreta. Each compartment connected by rate constants governing NP transport and fate. Extended Reversible Kinetics Implemented reversible transfer kinetics between compartments alongside irreversible processes (degradation, excretion). This captures the bidirectional movement of NPs between blood/tissue and accounts for NP release from cellular uptake. PEG-Coated Au NP Case Study Validated the model using PEG-coated gold nanoparticles (10.5 nm diameter) administered intravenously for lung targeting. Fitted model predictions against experimental biodistribution data, achieving a Sum of Deviations Index (SODI) of 0.88 (AAFE = 1.78). Sensitivity Analysis for Optimization Performed comprehensive sensitivity analysis to identify which kinetic parameters most strongly influence delivery efficiency. This enables rational design of NP formulations by highlighting the most impactful parameters for optimization. Cloud Deployment with REST API Deployed as a web application on the CompSafeNano Cloud Platform with RESTful API for programmatic access, enabling integration into NP design and optimization workflows. 0.88 Model Accuracy Sum of Deviations Index for PEG-Au NPs 5 Kinetic Framework Administration to excreta pathway 1.78 Fold Error Average absolute fold error vs. experimental IV → Lungs Delivery Route Intravenous to lung targeting validated Sensitivity Parameter Analysis Key parameters for delivery optimization REST API CompSafeNano Cloud-deployed with programmatic access
