From Microscale to Macroscale: Nine Orders of Magnitude for a Comprehensive Modeling of Hydrogels for Controlled Drug Delivery

Abstract

Because of their inherent biocompatibility and tailorable network design, hydrogels meet an increasing interest as biomaterials for the fabrication of controlled drug delivery devices. In this regard, mathematical modeling can highlight release mechanisms and governing phenomena, thus gaining a key role as complementary tool for experimental activity. Starting from the seminal contribution given by Flory–Rehner equation back in 1943 for the determination of matrix structural properties, over more than 70 years, hydrogel modeling has not only taken advantage of new theories and the increasing computational power, but also of the methods offered by computational chemistry, which provide details at the fundamental molecular level. Simulation techniques such as molecular dynamics act as a “computational microscope” and allow for obtaining a new and deeper understanding of the specific interactions between the solute and the polymer, opening new exciting possibilities for an in silico network design at the molecular scale. Moreover, system modeling constitutes an essential step within the “safety by design” paradigm that is becoming one of the new regulatory standard requirements also in the field-controlled release devices. This review aims at providing a summary of the most frequently used modeling approaches (molecular dynamics, coarse-grained models, Brownian dynamics, dissipative particle dynamics, Monte Carlo simulations, and mass conservation equations), which are here classified according to the characteristic length scale. The outcomes and the opportunities of each approach are compared and discussed with selected examples from literature.

Poly(vinyl alcohol) Hydrogels: The Old and New Functional Materials

“…With the swelling of the hydrogels due to the Donnan potential, the releasing time of drugs can be greatly prolonged while the dosage of the drug can be reduced [63,64]. Since PVA is stable to environmental stimulus, the releasing mechanism of drugs from PVA gels is proved and calculated as zero-order releasing mode [39,62,65,66]. As can be seen in Figure 4(a), PEG/PVA hydrogel system could perform stable releasing of aspirin under different pH buffer solutions [50].…”

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

“…[ 24,31 ] Concurrently, molecular self‐assemblies in peptides and proteins are moving from modulating cellular functionality in 3D context to the predictive creation of new biomimetic nanomaterials by bioengineering strategies at the molecular or atomic levels. [ 29,32 ] All in all, based on bottom‐up bioengineering strategies the predictive design and biomimetic capacity of designer self‐assembling peptide hydrogels would enhance the development of more physiological and reliable 3D cell models and help the biomedical industry to develop better molecular or cellular therapy approaches in tissue engineering, regenerative medicine, cancer management, or other biomedical applications.…”

Universal description of steric hindrance in flexible polymer gels

“…1 In many instances, the accurate prediction of drug release kinetics from gels and microgels also relies on the precise knowledge of the diffusion coefficient of the solute. [2][3][4] On the other hand, biopolymer-based hydrogels such as mucus or the extracellular matrix act as protective barriers against pathogens and toxic agents. 5 In spite of their relevance, the physical mechanisms that explain why only certain particles can permeate such barriers are not fully understood yet.…”