Drug Delivery Mechanisms of Poly(glycerol sebacate): An In-Depth Study of the Energetics at the Molecular Scale

Molecular simulations were carried out to investigate the mechanisms of drug delivery from poly(glycerol sebacate) (PGS). We simulated a number of key stages, from the encapsulation of the active pharmaceutical ingredients (API) in bulk PGS to their release into the water phase through the adsorption processes on the PGS surface. Caffeine, paracetamol, and ibuprofen were the studied APIs. Each stage of the API release was characterized by the calculation of a free energy property related to absorption, adsorption, or association. The free energy of absorption showed that the PGS material is able to accommodate APIs of different polarities and hydration properties due to the presence of hydrophobic and hydrophilic regions in the material. The free energy values of adsorption of the APIs on the PGS surface remain favorable, whereas the free energies of binding between APIs and glycerol, sebacic acid, and prepolymer molecules are weaker, thus indicating a possible release of the APIs into water from an energy viewpoint.