Mathematical Modeling And Numerical Simulation Of Drug Release Process Using Hydrogels As Carriers

Polymeric hydrogels are three-dimensional polymer networks in which individual hydrophilic polymer chains are connected, either by physical association or chemical bonds. As a typical kind of soft matter, once stimulated by environmental changes, hydrogels are able to respond intelligently and change their physical or chemical states. The macroscopical size and shape of hydrogels are controlled by the interactional forces of the molecules, which are functions of temperature, crosslink density of the polymer, solvent compositions, pH and so on. The intelligent responsiveness can be achieved by adjusting these factors to control the hydrogels change between swollen and collapsed states. Not only are hydrogels intelligent materials, but also they have excellent biocompatibility; all these properties make hydrogels ideal drug carriers for controlled release systems in the pharmaceuticals and biotechnology field.The primary purpose of drug delivery is to achieve efficient pharmacotherapy without side effects. Controlled drug release systems are those in which drug molecules are combined with the carrier materials physically or chemically, and then released at a specific location and a desirable rate, through diffusion or permeation to maximize the pharmacotherapy effect. In comparison with traditional delivery systems, controlled drug release systems provide more stable and desirable release. On one hand, there are smaller fluctuations of drug concentration in plasma and fewer adverse effects; on the other hand, the duration time of drug is elongated to avoid waste.Due to the complexity of the drug release process from polymeric hydrogels, with multi-disciplinary characteristic, it is extremely difficult to quantificationally describe and control the drug release process. Consequently, the mathematical modeling and numerical simulation play important roles in studying the release mechanisms and analyzing the principles of controlled drug release systems. On one side, these further the theoretical development of drug release mechanisms of polymeric hydrogel carriers, which drives the soft matter science to progress; on the other side, these works can provide guidance for the research and application of drug release from polymeric hydrogel carrier systems.In this work, firstly based on the multiphysics theory, a mathematical model of swelling-controlled drug release systems was established, in which the drug release process and the hydrogel swelling process were coupled through the extension of Fick’s law. By means of the finite element method, the effects of the initial drug concentration and other factors on the drug release process were studied and analyzed. In the meantime, a mathematical model of targeted drug delivery systems was established, and the effects of enzyme concentration and reaction rate on the drug release process were discussed. On the basis of continuous volume phase transition theory of polymeric hydrogels, preliminary and exploratory work has been done to simulate the swelling-controlled drug release process with up to150%hydrogels swelling degree. Based on the aforementioned researches, the mechanisms of drug release from polymeric hydrogels were revealed, and the evolution of the main parameters as well as the influences of dominating factors were discussed and analyzed, in the hope of propelling the development and application of polymeric hydrogels as drug carriers in the pharmaceuticals and biotechnology field.