Treatment of otitis media by transtympanic delivery of antibiotics.

Otitis media is the most common reason U.S. children receive antibiotics.

Synthesis, characterization, and in vivo efficacy of shell cross-linked nanoparticle formulations carrying silver antimicrobials as aerosolized therapeutics.

The use of nebulizable, nanoparticle-based antimicrobial delivery systems can improve efficacy and reduce toxicity for treatment of multi-drug-resistant bacteria in the chronically infected lungs of cystic fibrosis patients. Nanoparticle vehicles are particularly useful for applying broad-spectrum silver-based antimicrobials, for instance, to improve the residence time of small-molecule silver carbene complexes (SCCs) within the lung. Therefore, we have synthesized multifunctional, shell cross-linked knedel-like polymeric nanoparticles (SCK NPs) and capitalized on the ability to independently load the shell and core with silver-based antimicrobial agents.

Shell crosslinked knedel-like nanoparticles for delivery of cisplatin: effects of crosslinking.

Polymeric micelles and shell crosslinked knedel-like (SCK) nanoparticles were loaded with up to 48% (w/w) cisplatin. These spherical cisplatin-loaded nanoparticles displayed sustained platinum release over 5 days in PBS, enhanced stability over free cisplatin in aqueous milieu, and significant antitumor activity in vitro against two cancer cell lines.

Facile Synthesis of Clickable, Water-soluble and Degradable Polyphosphoesters.

"Click" chemistry is a library of efficient and reliable reactions, which have been used to functionalize various classes of bio- and synthetic macromolecular systems for the incorporation of designed properties and functions. In this report, azide-alkyne Huisgen cycloaddition and thiol-yne reactions, two classical "click" chemistries, were employed to functionalize biodegradable, clickable polyphosphoester homopolymers and their water-soluble copolymers. A stable alkyne-functionalized phospholane monomer was synthesized, its organocatalyzed polymerization kinetics were evaluated, and the resulting (co)polymers were utilized to develop this facile method that provides the synthesis of clickable, water-soluble and degradable polyphosphoesters, which can be adapted for various applications.

Paclitaxel-loaded SCK nanoparticles: an investigation of loading capacity and cell killing abilities in vitro.

Block copolymer nanoparticles having two different hydrodynamic diameters (120 nm vs 50 nm) and core diameters (60 nm vs 20 nm) with variable paclitaxel loading (5 to 20 wt % with respect to polymer weight, 4.4 μg/mL to 21.7 μg/mL paclitaxel concentrations in ultrapure water) were prepared for their in vitro cytotoxicity evaluation.

Synthetic polymer nanoparticles conjugated with FimH(A) from E. coli pili to emulate the bacterial mode of epithelial internalization.

Amphiphilic block copolymer nanoparticles are conjugated with uropathogenic Escherichia coli type 1 pilus adhesin FimH(A) through amidation chemistry to enable bladder epithelial cell binding and internalization of the nanoparticles in vitro.

Multicompartment polymer nanostructures with ratiometric dual-emission pH-sensitivity.

Pyrazine-labeled multicompartment nanostructures are shown to exhibit enhanced pH-responsive blue-shifted fluorescence emission intensities compared to their simpler core-shell spherical analogs. An amphiphilic linear triblock terpolymer of ethylene oxide, N-acryloxysuccinimide, and styrene, PEO(45)-b-PNAS(105)-b-PS(45), which lacks significant incompatibility for the hydrophobic block segments and undergoes gradual hydrolysis of the NAS units, underwent supramolecular assembly in mixtures of organic solvent and water to afford multicompartment micelles (MCMs) with a narrow size distribution. The assembly process was followed over time and found to evolve from individual polymer nanodroplets containing internally phase segregated domains, of increasing definition, and ultimately to dissociate into discrete micelles.

Evaluation of Isoprene Chain Extension from PEO Macromolecular Chain Transfer Agents for the Preparation of Dual, Invertible Block Copolymer Nanoassemblies.

Two RAFT-capable PEO macro-CTAs, 2 and 5 kDa, were prepared and used for the polymerization of isoprene which yielded well-defined block copolymers of varied lengths and compositions. GPC analysis of the PEO macro-CTAs and block copolymers showed remaining unreacted PEO macro-CTA. Mathematical deconvolution of the GPC chromatograms allowed for the estimation of the blocking efficiency, about 50% for the 5 kDa PEO macro-CTA and 64% for the 2 kDa CTA.

Tuning core vs. shell dimensions to adjust the performance of nanoscopic containers for the loading and release of doxorubicin.

Detailed studies were performed to probe the effects of the core and shell dimensions of amphiphilic, shell crosslinked, knedel-like polymer nanoparticles (SCKs) on the loading and release of doxorubicin (DOX), a widely-used chemotherapy agent, in aqueous buffer, as a function of the solution pH. Effects of the nanoparticle composition were held constant, by employing SCKs constructed from a single type of amphiphilic diblock copolymer, poly(acrylic acid)-b-polystyrene (PAA-b-PS). A series of four SCK nanoparticle samples, ranging in number-average hydrodynamic diameter from 14-30 nm, was prepared from four block copolymers having different relative block lengths and absolute degrees of polymerization.

Tunable dual-emitting shell-crosslinked nano-objects as single-component ratiometric pH-sensing materials.

Dual-emitting photonic nano-objects that can sense changes in the environmental pH are designed based on shell-crosslinked micelles assembled from amphiphilic block copolymers and crosslinked with pH-insensitive chromophores. The chromophoric crosslinkers are tetra-functionalized pyrazine molecules that bear a set of terminal aliphatic amine groups and a set of anilino amine groups, which demonstrate morphology-dependent reactivities towards the poly(acrylic acid) shell domain of the nano-objects. The extent to which the anilino amine groups react with the nano-object shell is shown to affect the hypsochromic shift (blue-shift).