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Cannabidiol (CBD) is viewed as a promising therapeutic agent against a variety of health ailments; however, its efficacy is limited by poor aqueous solubility. Amorphous solid dispersions (ASDs) can enhance the solubility of therapeutics by distributing them throughout a polymer matrix. In consideration of ASD formulations with CBD, we investigate the interactions of CBD with various polymers: poly(vinylpyrrolidone) (PVP), poly(vinylpyrrolidone)/vinyl acetate (PVP/VA) copolymer, hydroxypropyl methylcellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), and poly(methyl methacrylate) (PMMA). Both the experiment and molecular dynamics simulation reveal diverse mixing behavior among the set of polymers. Detailed structural and nanoscale interaction analyses suggest that positive deviations from ideal mixing behavior arise from the formation of stable polymer–CBD hydrogen bonds, whereas negative deviations are associated with disruptions to the polymer–polymer hydrogen bond network. Polymer–water interaction analyses indicate the significance of polymer hydrophobicity that can lead to poor dissolution of CBD. These results have implications for drug dissolution rates based on how CBD and water interact with each polymer. Furthermore, these insights may be used to guide ASD formulations for CBD or other small-molecule therapeutic agents.more » « lessFree, publicly-accessible full text available September 10, 2025
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Free, publicly-accessible full text available February 13, 2025
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Abstract Complex fibrillar networks mediate liquid–liquid phase separation of biomolecular condensates within the cell. Mechanical interactions between these condensates and the surrounding networks are increasingly implicated in the physiology of the condensates and yet, the physical principles underlying phase separation within intracellular media remain poorly understood. Here, we elucidate the dynamics and mechanics of liquid–liquid phase separation within fibrillar networks by condensing oil droplets within biopolymer gels. We find that condensates constrained within the network pore space grow in abrupt temporal bursts. The subsequent restructuring of condensates and concomitant network deformation is contingent on the fracture of network fibrils, which is determined by a competition between condensate capillarity and network strength. As a synthetic analog to intracellular phase separation, these results further our understanding of the mechanical interactions between biomolecular condensates and fibrillar networks in the cell.
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In addition to the repulsive and attractive interaction forces described by Derjaguin–Landau–Verwey–Overbeek (DLVO) theory, many charged colloid systems are stabilized by non-DLVO contributions stemming from specific material attributes. Here, we investigate non-DLVO contributions to the stability of polymer colloids stemming from the intra-particle glass transition temperature ( T g ). Flash nanoprecipitation is used to fabricate nanoparticles (NPs) from a library of polymers and dispersion stability is studied in the presence of both hydrophilic and hydrophobic salts. When adding KCl, stability undergoes a discontinuous decrease as T g increases above room temperature, indicating greater stability of rubbery NPs over glassy NPs. Glassy NPs are also found to interact strongly with hydrophobic phosphonium cations (PR 4 + ), yielding charge inversion and intermediate aggregation while rubbery NPs resist ion adsorption. Differences in the lifetime of ionic structuration within mobile surface layers is presented as a potential mechanism underlying the observed phenomenon.more » « less
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Functionalized cellulosics have shown promise as naturally derived thermoresponsive gelling agents. However, the dynamics of thermally induced phase transitions of these polymers at the lower critical solution temperature (LCST) are not fully understood. Here, with experiments and theoretical considerations, we address how molecular architecture dictates the mechanisms and dynamics of phase transitions for cellulose ethers. Above the LCST, we show that hydroxypropyl substituents favor the spontaneous formation of liquid droplets, whereas methyl substituents induce fibril formation through diffusive growth. In celluloses which contain both methyl and hydroxypropyl substituents, fibrillation initiates after liquid droplet formation, suppressing the fibril growth to a sub-diffusive rate. Unlike for liquid droplets, the dissolution of fibrils back into the solvated state occurs with significant thermal hysteresis. We tune this hysteresis by altering the content of substituted hydroxypropyl moieties. This work provides a systematic study to decouple competing mechanisms during the phase transition of multi-functionalized macromolecules.more » « less