Cardiac dysfunction following acute myocardial infarction (MI) is a major cause of death in the world and there is compelling need for new therapeutic strategies. In this report we demonstrate that a direct cardiac injection of drug-loaded microparticles, formulated from the polymer, poly(cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK), improves cardiac function following MI. Drug delivery vehicles have great potential to improve the treatment of cardiac dysfunction by sustaining high concentrations of therapeutics within the damaged myocardium. PCADK is unique from currently used polymers in drug delivery in that its hydrolysis generates neutral degradation products. We show here that PCADK causes minimal tissue inflammatory response, thus enabling PCADK for the treatment of inflammatory diseases, such as cardiac dysfunction. PCADK holds great promise for treating MI and other inflammatory diseases given its neutral, biocompatible degradation products and its ability to deliver a wide range of therapeutics.The development of drug delivery vehicles that can improve cardiac dysfunction following MI remains a major challenge in the field of biomaterials. Following acute MI, an excessive inflammatory response is initiated in the myocardium causing chronic elevation of inflammatory cytokines and reactive oxygen species, resulting in cardiac dysfunction 1,2,3,4 . A large number of clinically approved small molecule inhibitors have been identified that can suppress inflammation and have great potential for improving cardiac dysfunction. However, delivery remains a challenge as many of these drugs require large doses and daily injections for efficacy and cause toxicity at these high doses 5,6,7 . Thus, drug delivery vehicles that can sustain effective doses of therapeutics within the myocardium for weeks have the potential to slow or halt the progression of cardiac dysfunction 8 . Although biomaterials have been developed for treating cardiac dysfunction, these materials have been designed to deliver protein therapeutics and cells, and are not well suited for the controlled release of hydrophobic drugs, such as small molecule inhibitors, because of their large pore sizes 9 . Polyester-based microparticles do have the potential for delivering hydrophobic anti-inflammatory molecules; however their use in cardiac drug delivery has not been fully investigated.In this work, we demonstrate that microspheres formulated from the polymer, PCADK, which encapsulate the p38-inhibitor SB239063, can improve the treatment of MI. PCADK is a recently developed, acid-sensitive (supplemental Figure 1A) polymer that has great potential for treating inflammatory diseases, such as myocardial infarction, because it degrades into the neutral, excretable, FDA-approved compounds 1,4-cyclohexanedimethanol (approved by the FDA as an indirect food additive) and acetone (an endogenous compound with potential Correspondence should be addressed to: MED(E-mail: michael.davis@bme.emory.edu). antioxidant properties) and thus should not exacerbat...

BackgroundTuberculosis (TB) control is considered primarily a public health concern, and private sector TB treatment has attracted less attention. Thus, the size and characteristics of private sector TB drug sales remain largely unknown.Methodology/Principal FindingsWe used IMS Health data to analyze private TB drug consumption in 10 high burden countries (HBCs), after first mapping how well IMS data coverage overlapped with private markets. We defined private markets as any channels not used or influenced by national TB programs. Private markets in four countries – Pakistan, the Philippines, Indonesia and India – had the largest relative sales volumes; annually, they sold enough first line TB drugs to provide 65–117% of the respective countries' estimated annual incident cases with a standard 6–8 month regimen. First line drug volumes in five countries were predominantly fixed dose combinations (FDCs), but predominantly loose drugs in the other five. Across 10 countries, these drugs were available in 37 (loose drug) plus 74 (FDCs) distinct strengths. There were 54 distinct, significant first line manufacturers (range 2–11 per country), and most companies sold TB drugs in only a single study country. FDC markets were, however, more concentrated, with 4 companies capturing 69% of FDC volume across the ten countries. Among second line drugs, fluoroquinolones were widely available, with significant volumes used for TB in India, Pakistan and Indonesia. However, certain WHO-recommended drugs were not available and in general there were insufficient drug volumes to cover the majority of the expected burden of multidrug-resistant TB (MDR-TB).Conclusions/SignificancePrivate TB drug markets in several HBCs are substantial, stable, and complicated. This calls for appropriate policy and market responses, including expansion of Public-Private Mix (PPM) programs, greater reach, flexibility and appeal of public programs, regulatory and quality enforcement, and expansion of public MDR-TB treatment programs.

No abstract

We have designed a promising contact scheme to p-GaN, where Au/Ni/Au layers are deposited on p-GaN and annealed in air for 30 min at 470 °C to produce low-resistivity ohmic contacts. The Au layer in contact with p-GaN grows epitaxially via domain matching epitaxy, which acts as a template for NiO growth via lattice matching epitaxy. The 〈111〉 oriented gold rotates 30° in the basal (0001) plane of GaN by 30° with the following orientation relationship: [111]Au//[0001]GaN; [112̄]Au//[21̄1̄0]GaN. As a result, we can create epitaxial NiO–Au composite, where Au as well as NiO are in contact with p-GaN. This epitaxial composite structure is envisaged to be important in achieving low-resistivity ohmic contacts in p-GaN. We present the details of atomic structure, epitaxial relationship, chemistry, and electrical properties of ohmic contacts.