Surfactant-Polymer Complexation and Competition on Drug Nanocrystal Surfaces Control Crystallinity.

Nanosizing drug crystals has emerged as a successful approach to enabling oral bioavailability, as increasing drug crystal surface area improves dissolution kinetics and effective solubility. Recently, bottom-up methods have been developed to directly assemble nanosized crystals by leveraging polymer and surfactant excipients during crystallization to control crystal size, morphology, and structure. However, while significant research has investigated how polymers and other single additives inhibit or promote crystallization in pharmaceutical systems, there is little work studying the mechanistic interactions of multiple excipients on drug crystal structure and the extent of crystallinity, which can influence formulation performance. This study explores how the structure and crystallinity of a model hydrophobic drug crystal, fenofibrate, change as a result of competitive interfacial chemisorption between common nonionic surfactants (polysorbate 80 and sorbitan monooleate) and a surface-active polymer excipient (methylcellulose). Classical molecular dynamics simulations highlight how key intermolecular interactions, including surfactant-polymer complexation and surfactant screening of the crystal surface, modify the resulting crystal structure. In parallel, experiments generating drug nanocrystals in hydrogel thin films validate that drug crystallinity increases with an increasing weight fraction of surfactant. Simulation results reveal a connection between accelerated dynamics in the bulk crystal and the experimentally measured extent of crystallinity. To our knowledge, these are the first simulations that directly characterize structural changes in a drug crystal as a result of excipient surface composition and relate the experimental extent of crystallinity to structural changes in the molecular crystal. Our approach provides a mechanistic understanding of crystallinity in nanocrystallization, which can expand the range of orally deliverable small molecule therapies.

A Zwitterionic Hydrogel-Based Heterogeneous Fenton Catalyst for Water Treatment.

Persistent organic pollutants (POPs), including xenoestrogens and polyfluoroalkyl substances (PFAS), demand urgent global intervention. Fenton oxidation, catalyzed by iron ions, offers a cost-effective means to degrade POPs. However, numerous challenges like acid dependency, catalyst loss, and toxic waste generation hinder practical application. Efforts to create long-lasting heterogeneous Fenton catalysts, capable of simultaneously eliminating acid requirements, sustaining rapid kinetics, and retaining iron efficiently, have been unsuccessful. This study introduces an innovative heterogeneous zwitterionic hydrogel-based Fenton catalyst, surmounting these challenges in a cost-effective and scalable manner. The hydrogel, hosting individually complexed iron ions in a porous scaffold, exhibits substantial effective surface area and kinetics akin to homogeneous Fenton reactions. Complexed ions within the hydrogel can initiate Fenton degradation at neutral pH, eliminating acid additions. Simultaneously, the zwitterionic hydrogel scaffold, chosen for its resistance to Fenton oxidation, forms strong bonds with iron ions, enabling prolonged reuse. Diverging from existing designs, the catalyst proves compatible with UV-Fenton processes and achieves rapid self-regeneration during operation, offering a promising solution for the efficient and scalable degradation of POPs. The study underscores the efficacy of the approach by demonstrating the swift degradation of three significant contaminants-xenoestrogens, pesticides, and PFAS-across multiple cycles at trace concentrations.

Coarse-grained molecular dynamics simulations of immobilized micelle systems and their interactions with hydrophobic molecules.

Micelles immobilized in polymer materials are of emerging interest in drug delivery, water treatment and other applications. Immobilization removes the need for membrane-based separation to eliminate micelles from the medium, enabling facile extraction and delivery in diverse industries. This work lays out a coarse-grained molecular dynamics simulations framework for the rapid identification of surfactants for use in immobilized micelle systems. Micelles are immobilized by constraining one end of the constituent surfactants in space, mimicking what would occur in a copolymer system. We demonstrate that constraints affect how the micelles interact with small hydrophobic molecules, making it important to account for their effects in various drug-micelle and pollutant-micelle simulations. Our results show that in several systems there is stronger interaction between hydrophobic small molecules and micelles in immobilized systems compared to unconstrained systems. These strengthened interactions can have important implications for the design of new micelle-based extraction and delivery processes.

One-dimensional van der Waals heterostructures.

We present the experimental synthesis of one-dimensional (1D) van der Waals heterostructures, a class of materials where different atomic layers are coaxially stacked. We demonstrate the growth of single-crystal layers of hexagonal boron nitride (BN) and molybdenum disulfide (MoS2) crystals on single-walled carbon nanotubes (SWCNTs). For the latter, larger-diameter nanotubes that overcome strain effect were more readily synthesized. We also report a 5-nanometer-diameter heterostructure consisting of an inner SWCNT, a middle three-layer BN nanotube, and an outer MoS2 nanotube. Electron diffraction verifies that all shells in the heterostructures are single crystals. This work suggests that all of the materials in the current 2D library could be rolled into their 1D counterparts and a plethora of function-designable 1D heterostructures could be realized.