Subcutaneous Administration of a Zwitterionic Chitosan-Based Hydrogel for Controlled Spatiotemporal Release of Monoclonal Antibodies.

Subcutaneous (SC) administration of monoclonal antibodies (mAbs) is a proven strategy for improving therapeutic outcomes and patient compliance. The current FDA-/EMA-approved enzymatic approach, utilizing recombinant human hyaluronidase (rHuPH20) to enhance mAbs SC delivery, involves degrading the extracellular matrix's hyaluronate to increase tissue permeability. However, this method lacks tunable release properties, requiring individual optimization for each mAb. Seeking alternatives, physical polysaccharide hydrogels emerge as promising candidates due to their tunable physicochemical and biodegradability features. Unfortunately, none have demonstrated simultaneous biocompatibility, biodegradability, and controlled release properties for large proteins (≥150 kDa) after SC delivery in clinical settings. Here, a novel two-component hydrogel comprising chitosan and chitosan@DOTAGA is introduced that can be seamlessly mixed with sterile mAbs formulations initially designed for intravenous (IV) administration, repurposing them as novel tunable SC formulations. Validated in mice and nonhuman primates (NHPs) with various mAbs, including trastuzumab and rituximab, the hydrogel exhibited biodegradability and biocompatibility features. Pharmacokinetic studies in both species demonstrated tunable controlled release, surpassing the capabilities of rHuPH20, with comparable parameters to the rHuPH20+mAbs formulation. These findings signify the potential for rapid translation to human applications, opening avenues for the clinical development of this novel SC biosimilar formulation.

Feasibility study and direct extraction of endogenous free metallic cations combining hemodialysis and chelating polymer.

In this article, we report the conception and the use of dialysis-based medical device for the extraction of metals. The medical device is obtained by addition in the dialysate of a functionalized chitosan that can chelate endogenous metals like iron or copper. This water-soluble functionalized chitosan is obtained after controlled reacetylation and grafting of DOTAGA. Due to the high mass of chitosan, the polymer cannot cross through the membrane and the metals are trapped in the dialysate during hemodialysis. Copper extraction has been evaluated in vitro using an hemodialysis protocol. Feasibility study has been performed on healthy sheep showing no acute toxicity througout the entire dialysis procedure and first insights of metallic extraction even on healthy animals.

Design of Hybrid PAH Nanoadsorbents by Surface Functionalization of ZrO2 Nanoparticles with Phosphonic Acids.

This study focuses on the preparation of innovative nanocomposite materials based on surface modification of commercial nano-ZrO2 optimized from Brønsted acid-base surface reactions. This surface modification was carried out by direct grafting of suitable phosphonic acids bearing a vinylic or phenylic substituent in aqueous solution. Different loading quantities of the anchoring organophosphorus compounds were applied for each materials synthesis. The resulting nanohybrids were thoroughly characterized by infrared spectroscopy (DRIFT), solid-state nuclear magnetic resonance (NMR), nitrogen adsorption-desorption (BET), thermogravimetric analysis (TG), and X-ray photoelectron spectroscopy (XPS), demonstrating the reliability and efficient tunability of the surface functionalization based on the starting Zr/P ratio. Our nanocomposite materials exhibited a high specific surface area as well as complex porosity networks with well-defined meso-pore. The as-prepared materials were investigated for the adsorption of a mixture of 16 polycyclic aromatic hydrocarbons (PAHs) at 200 ng·mL-1 in an aqueous solution. Adsorption kinetics experiments of each individual material were carried out on the prepared PAHs standard solution for a contact time of up to 6 h. Pretreatments of the adsorption test samples were performed by solid-phase extraction (SPE), and the resulting samples were analyzed using an ultrasensitive GC-orbitrap-MS system. The pseudo-first-order and the pseudo-second-order models were used to determine the kinetic data. The adsorption kinetics were best described and fitted by the pseudo-second-order kinetic model. The correlation between the nature of the substituent (vinylic or phenylic) and the parameters characterizing the adsorption process were found. In addition, an increase of PAHs adsorption rates with phosphonic acid loading was observed.