Impact of Hydroxypropyl Methylcellulose Acetate Succinate Critical Aggregation Concentration on Celecoxib Supersaturation.

Polymers play an important role in amorphous solid dispersions (ASDs), enhancing stability in the solid state and maintaining supersaturation in aqueous solutions of intrinsically low-water-soluble drug candidates. Hydroxypropyl methylcellulose acetate succinate (HPMCAS) is widely used in ASDs due to its hydrophobic/hydrophilic balance and ionizability of the substituent functionalities. While colloid formation of HPMCAS in solution due to this hydrophobic/hydrophilic balance has been studied, the impact of the polymer conformation (random coil vs aggregated) on drug supersaturation of ASDs is not well understood. To our knowledge, this is the first report where the critical aggregation concentration for three grades of HPMCAS (HF/MF/LF) has been determined via fluorescence spectroscopy using the environment-sensitive probe pyrene. The specific impact of polymer conformation (random coil vs aggregate) on the model drug celecoxib (CLX) has been elucidated with fluorescence quenching and nuclear magnetic resonance (NMR) spectroscopy. A negative deviation of the Stern-Volmer plot indicated that aggregated HPMCAS effectively blocked the quencher's access to CLX. This is further supported by NMR observations, where NMR spectra indicate a larger change of chemical shift of the -NH group of CLX when HPMCAS is above its aggregated concentration, suggesting strong H-bonding interactions between aggregated HPMCAS and CLX. Finally, the supersaturation-precipitation study shows that all three grades of HPMCAS in the aggregated state significantly enhanced CLX supersaturation compared to the nonaggregated state, indicating that polymer aggregation plays a critical role in maintaining drug supersaturation.

Effects of Stereochemistry and Hydrogen Bonding on Glycopolymer-Amyloid-ß Interactions.

Saccharide stereochemistry plays an important role in carbohydrate functions such as biological recognition processes and protein binding. Synthetic glycopolymers with pendant saccharides of controlled stereochemistry provide an attractive approach for the design of polysaccharide-inspired biomaterials. Acrylamide-based polymers containing either ß,d-glucose or ß,d-galactose pendant groups, designed to mimic GM1 ganglioside saccharides, and their small-molecule analogues were used to evaluate the effect of stereochemistry on glycopolymer solution aggregation processes alone and in the presence of Aß42 peptide using dynamic light scattering, gel permeation chromatography-multiangle laser light scattering, and fluorescence assays. Fourier transform infrared and nuclear magnetic resonance (NMR) were employed to determine hydrogen bonding patterns of the systems. The galactose-containing polymer displayed significant intramolecular hydrogen bonding and self-aggregation and minimal association with Aß42, while the glucose-containing glycopolymers showed intermolecular interactions with the surrounding environment and association with Aß42. Saturation transfer difference NMR spectroscopy demonstrated different binding affinities for the two glycopolymers to Aß42 peptide.

Aqueous RAFT Synthesis of Low Molecular Weight Anionic Polymers for Determination of Structure/Binding Interactions with Gliadin.

Gliadin, a component of gluten and a known epitope, is implicated in celiac disease (CeD) and results in an inflammatory response in CeD patients when consumed. Acrylamide-based polyelectrolytes are employed as models to determine the effect of molecular weight and pendent group on non-covalent interaction modes with gliadin in vitro. Poly(sodium 2-acrylamido-2-methylpropane sulfonate) and poly(sodium 3-methylpropyl-3-butanoate) are synthesized via aqueous reversible addition fragmentation chain transfer (aRAFT) polymerization and characterized by gel permeation chromatography-multiangle laser light scattering. The polymer/gliadin blends are examined via circular dichroism, zeta potential measurements, 8-anilinonaphthalene-1-sulfonic acid fluorescence spectroscopy, and dynamic light scattering. Acrylamide polymers containing strong anionic pendent groups have a profound effect on gliadin secondary structure and solution behavior below the isoelectric point, while polymers containing hydrophobic character only have a minor impact. The polymers have little effect on gliadin secondary structure and solution behavior at the isoelectric point.

Enhanced Surface Properties of Branched Poly(ether sulfone) from Semifluorinated Polyhedral Oligomeric Silsequioxanes.

Hybrid systems in which poly(ether sulfone) (PESU) chains are grafted to semifluorinated polyhedral oligomeric silsesquioxane (POSS) cores are expected to integrate the advantages of both fluoropolymers and POSS into the polymer system to yield excellent surface properties. For that purpose, we synthesized a novel octa-functional perfluorocyclopentenyl-POSS (PFCP-POSS), which was used as a "core" grafting point. Commercial PESU was successfully grafted to PFCP-POSS via the nucleophilic addition-elimination reaction between the phenolic chain ends and reactive PFCP moieties to yield a hybrid branched polymer possessing a semifluorinated POSS core. X-ray photoelectron spectroscopy, neutron reflectivity, and atomic force microscopy indicated that the preparation of nanostructured polymer surfaces occurs by migration of the low surface energy components (PFCP-POSS molecules), while POSS aggregation is suppressed by covalent attachment to the long PESU chains. The resulting PFCP-POSS modified PESU films were highly transparent and yielded hydrophobic surfaces with low surface energy and high modulus for potential applications in high performance coatings and composites.