Controlled release of entrapped nanoparticles from thermoresponsive hydrogels with tunable network characteristics

Abstract

Thermoresponsive hydrogels have been studied intensively for creating smart drug carriers and controlled drug delivery. Understanding the drug release kinetics and corresponding transport mechanisms of nanoparticles (NPs) in a thermoresponsive hydrogel network is the key to the successful design of a smart drug delivery system. To investigate the anomalous NP diffusion in smart hydrogels with tunable network characteristics, we construct an energy-conserving dissipative particle dynamics model of rigid NPs entrapped in a hydrogel network in an aqueous solution, where the hydrogel network is formed by cross-linked semiflexible polymers of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM). By varying the environmental temperature crossing the lower critical solution temperature of PNIPAM we can significantly change the hydrogel network characteristics. We systematically investigate how the matrix porosity of the hydrogel and the nanoparticle size affect the NPs' diffusion process and NPs' release kinetics at different temperatures. Quantitative results on the mean-squared displacement and the van Hove displacement distributions of NPs show that all NPs entrapped in the smart hydrogels undergo subdiffusion at both low and high temperatures. For a coil state and as the system temperature approaches the critical temperature of the coil-to-globule phase transition, both the subdiffusive exponent and the diffusion coefficient of NPs increase due to the increased kinetic energy and the decreased confinement on NPs, while the transport of NPs in the hydrogels can be also enhanced by decreasing the matrix porosity of the polymer network and NPs' size. However, when the solution temperature is increased above the critical temperature, the hydrogel network collapses following the coil-to-globule transition, with the NPs tightly trapped in some local regions inside the hydrogels. Consequently, the NP diffusion coefficient can be reduced by two orders of magnitude, or the diffusion processes can even be completely stopped. These findings provide new insights for designing controlled drug release from stimuli-responsive hydrogels, including autonomously switch on/off drug release to respond to the changes of the local environment.

Dynamics of nanoparticles in polydisperse polymer networks: From free diffusion to hopping

“…2 We note, however, that the two approaches predict qualitatively different behaviors for the relevant dynamical quantities, such as the NP diffusion coefficient as a function of C, see below for details. The importance of the confinement parameter for the description of the diffusion of NPs in polymer networks has also been confirmed in experiments 14,15,[52][53][54][55] and simulations. [42][43][44] However, even recent simulations 43,44 have not explored the strong confinement regime, C 3, due to the extremely slow dynamics that characterizes it and hence the dynamics of the NP in this range of parameters is at present not known.…”

Fractional Modeling in Action: A Survey of Nonlocal Models for Subsurface Transport, Turbulent Flows, and Anomalous Materials

“…We point out interesting research directions that could involve the use of variableand distributed-order differential equations in the multi-scale modeling of materials. Recently, nano-scale simulation studies on trapping of nano-particles in hydrogel networks indicated a time-temperature dependency of the MSD in the evolution of anomalous diffusion regimes, where a subdiffusion regime has been found to be of transitional nature at intermediate time scales, with ballistic/normal diffusion dynamics for short/long time scales [236]. This motivates the study of variable-order models in time to compactly describe the macroscopic rheological evolution of such polymer networks.…”

Smart Polymers for Advanced Applications: A Mechanical Perspective Review

“…Two different mechanisms have been identified for the self-aggregation of temperature-responsive polymers during the coil-to-globule phase transition process, which is found to be dependent on the size of these polymer chains. Such a DPD model has been furthered applied to study the transport mechanisms of nanoparticles (NPs) in a thermoresponsive PNIPAM hydrogel network (Wang et al, 2020). By changing the simulation temperature across the LCTS of PNIPAM, the hydrogel network characteristics can be significantly altered, leading to the controlled release behaviors of entrapped NPs.…”