Nanoscopic gel particle for intra-articular injection formulation.

Hyaluronic acid (HA) based nanogels showed effective intracellular delivery efficacy for anti-cancer and anti-inflammatory drugs, characterized by their ability targeting relevant cell receptors. In the present study, we demonstrate the ability of hyaluronic acid-polyethyleneimine (HA-PEI) nanogels as a promising dual-functional interfacial active for intra-articular injection to intervene arthritis. Nanomechanical measurements on both model substrates and human cartilage samples confirm that the HA-PEI nanogels can significantly improve interfacial lubrication, in comparison to HA molecules, or silica-based nanoparticles. We show that the Coefficient of Friction significantly decreases with a decreasing nanogel size. The exceptional lubricating performance, coupled with the proven drug delivery capability, evidences the great potential of nanoscopic hydrogels for early-stage arthritis treatment. The flexibility in choosing the chemical nature, molecular architecture, and structural characteristics of nanogels makes it possible to modulate both drug delivery kinetics and interfacial lubrication, thus representing an innovative approach to treat degenerative joint diseases.

Diversity-induced decoherence.

We analyze the effect of small-amplitude noise and heterogeneity in a network of coupled excitable oscillators with strong timescale separation. Using mean-field analysis, we uncover the mechanism of a nontrivial effect-diversity-induced decoherence (DIDC)-in which heterogeneity modulates the mechanism of self-induced stochastic resonance to inhibit the coherence of oscillations. We argue that DIDC may offer one possible mechanism via which, in excitable neural systems, generic heterogeneity and background noise can synergistically prevent unwanted resonances that may be related to hyperkinetic movement disorders.

Droplet-based microfluidic synthesis of nanogels for controlled drug delivery: tailoring nanomaterial properties via pneumatically actuated flow-focusing junction.

Conventional batch syntheses of polymer-based nanoparticles show considerable shortcomings in terms of scarce control over nanomaterials morphology and limited lot-to-lot reproducibility. Droplet-based microfluidics represents a valuable strategy to overcome these constraints, exploiting the formation of nanoparticles within discrete microdroplets. In this work, we synthesized nanogels (NGs) composed of hyaluronic acid and polyethyleneimine using a microfluidic flow-focusing device endowed with a pressure-driven micro-actuator. The actuator achieves real-time modulation of the junction orifice width, thereby regulating the microdroplet diameter and, as a result, the NG size. Acting on process parameters, NG hydrodynamic diameter could be tuned in the range 92-190 nm while preserving an extremely low polydispersity (0.015); those values are hardly achievable in batch syntheses and underline the strength of our toolbox for the continuous in-flow synthesis of nanocarriers. Furthermore, NGs were validated in vitro as a drug delivery system in a representative case study still lacking an effective therapeutic treatment: ovarian cancer. Using doxorubicin as a chemotherapeutic agent, we show that NG-mediated release of the drug results in an enhanced antiblastic effect vs. the non-encapsulated administration route even at sublethal dosages, highlighting the wide applicability of our microfluidics-enabled nanomaterials in healthcare scenarios.

Hubs, diversity, and synchronization in FitzHugh-Nagumo oscillator networks: Resonance effects and biophysical implications.

Using the FitzHugh-Nagumo equations to represent the oscillatory electrical behavior of ß-cells, we develop a coupled oscillator network model with cubic lattice topology, showing that the emergence of pacemakers or hubs in the system can be viewed as a natural consequence of oscillator population diversity. The optimal hub to nonhub ratio is determined by the position of the diversity-induced resonance maximum for a given set of FitzHugh-Nagumo equation parameters and is predicted by the model to be in a range that is fully consistent with experimental observations. The model also suggests that hubs in a ß-cell network should have the ability to "switch on" and "off" their pacemaker function. As a consequence, their relative amount in the population can vary in order to ensure an optimal oscillatory performance of the network in response to environmental changes, such as variations of an external stimulus.