Multiscale Computational Framework for the Liquid-Liquid Phase Separation of Intrinsically Disordered Proteins.

The reversible assembly of intrinsically disordered proteins (IDPs) to form membraneless organelles (MLOs) is a fundamental process involved in the spatiotemporal regulation in living cells. MLOs formed via liquid-liquid phase separation (LLPS) serve as molecule-enhancing hubs to regulate cell functions. Owing to the complexity and dynamic nature of the protein assembly via a network of weak inter- and intra-molecular interactions, it is challenging to describe and predict the LLPS behavior.

Stochastic Lattice-Based Modeling of Macromolecule Release from Degradable Hydrogel.

A three-dimensional lattice-based model has been developed to describe the release of a macromolecular drug encapsulated in a degradable hydrogel. The degradation-induced network heterogeneity is considered by assigning varying diffusion coefficients to the lattice sites based on the fitted exponential node-diffusivity relationship. As time passes, due to the degradation of crosslink nodes, diffusivity values in lattice sites progress to higher values.

Controllable multi-phase protein release from in-situ hydrolyzable hydrogel.

Using hydrogels to control the long-term release of protein remains challenging, especially for in-situ forming formulations. The uncontrollable burst release in the initial phase, the halted release in the subsequent phase, and the undesired drug dumping at the late stage are some obstacles hydrogel-based depots commonly encounter. In this study, we report hydrolyzable dextran-based hydrogels crosslinked by Michael addition to demonstrate a systematic solution to solve these problems.

Dual-Diffusivity Stochastic Model for Macromolecule Release from a Hydrogel.

A three-dimensional model has been developed to describe the multiphase release of macromolecular drugs encapsulated in a hydrogel. The heterogeneity of network mesh size was considered by assigning varying diffusion coefficients to the network lattices randomly. Using a stochastic approach, the random nature of diffusion of drug molecules was captured within the network.

Local environment-dependent kinetics of ester hydrolysis revealed by direct H NMR measurement of degrading hydrogels.

We have demonstrated the use of a simple H NMR spectrometry-based method to directly measure the pseudo first-order hydrolytic cleavage rate constant (k) of methacrylate-derived ester crosslinkers in hydrogels composed of PEG, dextran, carboxymethyl dextran (CM-dextran) and hyaluronic acid (HA). Using this technique, we systematically examined how the local environment in the hydrogel influenced the rate of ester hydrolysis. Within the formulations being studied, the esters in the crosslinked polymer network (gel state) degraded 1.

Controlled release technology for anti-angiogenesis treatment of posterior eye diseases: Current status and challenges.

Antiangiogenic therapeutics, such as corticosteroids, VEGF targeting antibodies and aptamers have been demonstrated effective in controlling retinal and choroidal neovascularization related vision loss. However, to manage the chronic conditions, it requires long term and frequent intravitreal injections of these drugs, resulting in poor patient compliance and suboptimal treatment. In addition, emerging drugs such as tyrosine kinase inhibitors and siRNAs received much expectations, but the late stage clinical trials encountered various obstacles.