Scaling Laws in the Diffusive Release of Neutral Cargo from Hollow Hydrogel Nanoparticles: Paclitaxel-Loaded Poly(4-vinylpyridine)

Abstract

We study the nonequilibrium diffusive release of electroneutral molecular cargo encapsulated inside hollow hydrogel nanoparticles. We propose a theoretical model that includes osmotic, steric, and short-range polymer−cargo attractions to determine the effective cargo−hydrogel interaction, u eff *, and the effective diffusion coefficient of the cargo inside the polymer network, D eff *. Using dynamical density functional theory (DDFT), we investigate the scaling of the characteristic release time, τ 1/2 , with the key parameters involved in the process, namely, u eff *, D eff *, and the swelling ratio. This effort represents a full study of the problem, covering a broad range of cargo sizes and providing predictions for repulsive and attractive polymer shells. Our calculations show that the release time through repulsive polymer networks scales with q 2 e βu eff * /D eff * for βu eff * ≫ 1. In this case, the cargo molecules are excluded from the shell of the hydrogel. For attractive shells, the polymer retains the cargo molecules on its internal surface and its interior, and the release time grows exponentially with the attraction strength. The DDFT calculations are compared to an analytical model for the mean first passage time, which provides an excellent quantitative description of the kinetics for both repulsive and attractive shells without fitting parameters. Finally, we apply the method to reproduce experimental results on the release of paclitaxel from hollow poly(4-vinylpyridine) nanoparticles and find that the slow release of the drug can be explained in terms of the strong binding attraction between the drug and the polymer.

Amphiphilic and Biocompatible DNA Origami‐Based Emulsion Formation and Nanopore Release for Anti‐Melanogenesis Therapy

“…The binding affinity between the DNA origami and arbutin or coumaric acid attracted them to the binding sites, preventing the burst diffusivity at the initial stage. [48] At this moment, the DNA origami acted as the warehouse of excess arbutin and coumaric acid storage through the binding process. Subsequently, the dissociation process resulted in the sustained release profiles with steady rates.…”

Permeability of Polymer Membranes beyond Linear Response

“…The permeability of polymeric membranes is a key functional property in biology and modern applications utilizing soft materials. Examples of polymer networks important for selective transport in living systems are cytoskeletons, mucus, and extracellular matrices. − Synthetic polymer networks, on the other hand, serve as indispensable building blocks in dialysis, nanofiltration and desalination, drug delivery systems − or stimuli-responsive nanoreactors with applications in controllable nanocatalysis, − and biomedical diagnoses. − The transport embraces nanoscale atoms to sub-micron-scale macromolecules, such as ions, ligands, proteins, and reactants, which we refer to as “penetrants” of the membrane in the following. Particularly important for applications is to utilize solute selectivity in the permeability (“permselectivity”), as prominently found in air filtration or gas separation − and water purification. − …”

Phenol release from pNIPAM hydrogels: scaling molecular dynamics simulations with dynamical density functional theory

“…For an infinitely dilute cargo system, this free energy equals the effective interaction difference between the two bulks and the molecule, u eff , and dictates the partition coefficient (the concentration ratio between two bulks at thermodynamic equilibrium), a central quantity to design capsules and membranes with different materials and purposes. [26][27][28][29][30][31][32][33][34] However, DG trans is a thermodynamic property and does not provide information about how long it takes to load or release the cargo from a given capsule or the mass flux across a membrane. Consequently, we also need a transport property, the diffusion coefficient, D, to access the load (or release) kinetics.…”

“…MD simulations allow us to determine directly DG trans and D. DDFT is a theory able to predict the time evolution of the non-equilibrium density profiles of the cargo concentration, 43 and has been applied successfully to similar problems. 32,33,44,45 We use the values of DG trans and D obtained from MD simulations as the input parameters to obtain the time evolution of the cargo concentration. In particular, we calculate DG trans for several representative small cargo molecules, namely methane, phenol, and 5-fluorouracil (5-FU).…”