Thermodynamics of Polymer Drug Interactions: An Influential Factor for the Development of a Stable Drug Delivery System

Polymer-drug interactions play a pivotal role in the design and optimization of drug delivery systems. Thermodynamic principles, such as enthalpy, entropy and free energy, govern these interactions and significantly influence the stability, efficacy and release profiles of the drug-polymer complexes. In this review we explore the role of thermodynamics in drug-polymer binding, focusing on non-covalent interactions, including van der Waals forces, hydrogen bonding, ionic interactions and hydrophobic effects. These interactions affect the drug encapsulation efficiency, release kinetics and the overall stability of the delivery system. Understanding the balance between the various thermodynamic forces helps in the rational design of advanced drug delivery platforms, such as nanoparticles, micelles and hydrogels, which rely on optimized drug-polymer affinity. Our review further delves into the experimental techniques and modeling approaches used to characterize these interactions, such as isothermal titration calorimetry (ITC), molecular dynamics (MD) simulations and surface plasmon resonance (SPR). By examining these thermodynamic foundations, we believe this article provides insights into developing more efficient and stable drug delivery systems that ensure targeted release, enhanced bioavailability and reduced side effects.