Functional Polycarbonate of a d‑Glucal-Derived Bicyclic Carbonate via Organocatalytic Ring-Opening Polymerization

Herein, we demonstrate the synthesis of a bicyclic carbonate monomer of a d-glucal derivative, which originated from the natural product d-glucose, in an efficient three-step procedure and its ring-opening polymerization (ROP), initiated by 4-methylbenzyl alcohol, via organocatalysis. The ROP behavior was studied as a function of time, catalyst type, and catalyst concentration by using size exclusion chromatography (SEC) and nuclear magnetic resonance (NMR) spectroscopy. Using a cocatalyst system of 1,8-diazabicyclo[5.4.0]­undec-7-ene and 1-(3,5-bis­(trifluoromethyl)­phenyl)-3-cyclohexyl-2-thiourea (5 mol %) afforded poly­(d-glucal-carbonate) (PGCC) with almost complete monomer conversion (ca. 99%) within 1 min, as analyzed by ¹H NMR spectroscopy, and a monomodal SEC trace with dispersity of 1.13. The resulting PGCCs exhibited amorphous characteristics with a relatively high glass transition temperature at ca. 69 °C and onset decomposition temperature at ca. 190 °C, as analyzed by differential scanning calorimetry and thermogravimetric analysis, respectively. This new type of potentially degradable polymer system represents a reactive functional polymer architecture

Holistic Assessment of Covalently Labeled Core–Shell Polymeric Nanoparticles with Fluorescent Contrast Agents for Theranostic Applications

The successful development of degradable polymeric nanostructures as optical probes for use in nanotheranostic applications requires the intelligent design of materials such that their surface response, degradation, drug delivery, and imaging properties are all optimized. In the case of imaging, optimization must result in materials that allow differentiation between unbound optical contrast agents and labeled polymeric materials as they undergo degradation. In this study, we have shown that use of traditional electrophoretic gel-plate assays for the determination of the purity of dye-conjugated degradable nanoparticles is limited by polymer degradation characteristics. To overcome these limitations, we have outlined a holistic approach to evaluating dye and peptide–polymer nanoparticle conjugation by utilizing steady-state fluorescence, anisotropy, and emission and anisotropy lifetime decay profiles, through which nanoparticle–dye binding can be assessed independently of perturbations, such as those presented during the execution of electrolyte gel-based assays. This approach has been demonstrated to provide an overall understanding of the spectral signature–structure–function relationship, ascertaining key information on interactions between the fluorophore, polymer, and solvent components that have a direct and measurable impact on the emissive properties of the optical probe. The use of these powerful techniques provides feedback that can be utilized to improve nanotheranostics by evaluating dye emissivity in degradable nanotheranostic systems, which has become increasingly important as modern platforms transition to architectures intentionally reliant on degradation and built-in environmental responses

Preparation and <i>in Vitro</i> Antimicrobial Activity of Silver-Bearing Degradable Polymeric Nanoparticles of Polyphosphoester-<i>block</i>-Poly(l‑lactide)

The development of well-defined polymeric nanoparticles (NPs) as delivery carriers for antimicrobials targeting human infectious diseases requires rational design of the polymer template, an efficient synthetic approach, and fundamental understanding of the developed NPs, <i>e.g.,</i> drug loading/release, particle stability, and other characteristics. Herein, we developed and evaluated the <i>in vitro</i> antimicrobial activity of silver-bearing, fully biodegradable and functional polymeric NPs. A series of degradable polymeric nanoparticles (dNPs), composed of phosphoester and l-lactide and designed specifically for silver loading into the hydrophilic shell and/or the hydrophobic core, were prepared as potential delivery carriers for three different types of silver-based antimicrobials–silver acetate or one of two silver carbene complexes (SCCs). Silver-loading capacities of the dNPs were not influenced by the hydrophilic block chain length, loading site (<i>i.e.</i>, core or shell), or type of silver compound, but optimization of the silver feed ratio was crucial to maximize the silver loading capacity of dNPs, up to <i>ca.</i> 12% (w/w). The release kinetics of silver-bearing dNPs revealed 50% release at <i>ca.</i> 2.5–5.5 h depending on the type of silver compound. In addition, we undertook a comprehensive evaluation of the rates of hydrolytic or enzymatic degradability and performed structural characterization of the degradation products. Interestingly, packaging of the SCCs in the dNP-based delivery system improved minimum inhibitory concentrations up to 70%, compared with the SCCs alone, as measured <i>in vitro</i> against 10 contemporary epidemic strains of Staphylococcus aureus and eight uropathogenic strains of Escherichia coli. We conclude that these dNP-based delivery systems may be beneficial for direct epithelial treatment and/or prevention of ubiquitous bacterial infections, including those of the skin and urinary tract