Hyperbranched polydendrons: a new controlled macromolecular architecture with self-assembly in water and organic solvents

A new macromolecular architecture (hyperbranched polydendrons) is presented. Combining aspects of linear-dendritic hybrids, controlled radical polymerisation and branched vinyl polymerisation, the materials have very high molecular weight (Mw > 1 MDa) and surface functionality. Although dispersities are broad (Đ up to 25) the structures behave with remarkable uniformity upon manipulation of solvent environment. Comparisons of conventional linear-dendritic hybrids and hyperbranched polydendrons are presented, including aspects of their synthesis. Under solvent exchange in organic media, a reversible self-assembly to form monodispersed nanoparticles (PDI as low as 0.013) is observed. Self-assembly and encapsulation is also observed during aqueous nanoprecipitation of the hyperbranched materials, with nanoparticle size (diameters from 60–140 nm) controlled through modification of precipitation conditions and the generation of the ideally branched dendrons at one end of each primary chain. The aqueous nanoparticles are highly stable and offer considerable opportunities for tailored functionality and future advanced applications.</div

Using Dynamic Oral Dosing of Rifapentine and Rifabutin to Simulate Exposure Profiles of Long-Acting Formulations in a Mouse Model of Tuberculosis Preventive Therapy

Administration of tuberculosis preventive therapy (TPT) to individuals with latent tuberculosis infection is an important facet of global tuberculosis control. The use of long-acting injectable (LAI) drug formulations may simplify and shorten regimens for this indication. Rifapentine and rifabutin have antituberculosis activity and physiochemical properties suitable for LAI formulation, but there are limited data available for determining the target exposure profiles required for efficacy in TPT regimens. The objective of this study was to determine exposure-activity profiles of rifapentine and rifabutin to inform development of LAI formulations for TPT. We used a validated paucibacillary mouse model of TPT in combination with dynamic oral dosing of both drugs to simulate and understand exposure-activity relationships to inform posology for future LAI formulations. This work identified several LAI-like exposure profiles of rifapentine and rifabutin that, if achieved by LAI formulations, could be efficacious as TPT regimens and thus can serve as experimentally determined targets for novel LAI formulations of these drugs. We present novel methodology to understand the exposure-response relationship and inform the value proposition for investment in development of LAI formulations that have utility beyond latent tuberculosis infection

Development of branching in living radical copolymerization of vinyl and divinyl monomers

The branching copolymerization of 2-hydroxypropyl methacrylate ( HPMA) with either ethylene glycol dimethacrylate (EGDMA) or bisphenol A dimethacrylate (BPDMA) as the branching agent has been carried out using atom transfer radical polymerization (ATRP) in methanol at 20 C. With EGDMA, soluble branched copolymers were obtained provided that less than one branching agent was incorporated per primary chain: higher levels of EGDMA led to gelation, as expected. Analysis of the changes in the molecular weight and polydispersity of the polymers shows that the formation of highly branched chains occurs only at high (&gt; 90%) conversions. Chain coupling is close to the ideal behavior predicted by the Flory-Stockmayer theory, suggesting that all double bonds are equally reactive and that there is no significant cyclization, in contrast to conventional free radical polymerization. This analysis is confirmed by comparison of the consumption of the EGDMA branching agent with predictions from both theory and simulation. With BPDMA as the branching agent, similar results are obtained although branching is slightly less efficient

POLY 310-Direct Synthesis of Anisotropic Polymer Nanoparticles by ATRP

No abstract available

POLY 310-Direct Synthesis of Anisotropic Polymer Nanoparticles by ATRP

No abstract available

POLY 268-Direct Synthesis of Anisotropic Polymer Nanoparticles

No abstract available

POLY 268-Direct Synthesis of Anisotropic Polymer Nanoparticles

No abstract available