Synthesis, characterization, and in vitro transfection activity of charge-reversal amphiphiles for DNA delivery.

A series of charge-reversal lipids were synthesized that possess varying chain lengths and end functionalities. These lipids were designed to bind and then release DNA based on a change in electrostatic interaction with DNA. Specifically, a cleavable ester linkage is located at the ends of the hydrocarbon chains. The DNA release from the amphiphile was tuned by altering the length and position of the ester linkage in the hydrophobic chains of the lipids through the preparation of five new amphiphiles. The amphiphiles and corresponding lipoplexes were characterized by DSC, TEM, and X-ray, as well as evaluated for DNA binding and DNA transfection. For one specific charge-reversal lipid, stable lipoplexes of approximately 550 nm were formed, and with this amphiphile, effective in vitro DNA transfection activities was observed.

Synthesis and characterization of dendron cross-linked PEG hydrogels as corneal adhesives.

In pursuit of a wound-specific corneal adhesive, hydrogels formed by the reaction of propionaldehyde, butyraldehyde, or 2-oxoethyl succinate-functionalized poly(ethylene glycol) (PEG) with a peptide-based dendritic cross-linker (Lys(3)Cys(4)) were characterized. These macromers react within minutes of mixing to form transparent and elastic hydrogels with in vitro degradation times that range from hours to months based on the type of bonds formed during the cross-linking reaction, either thiazolidine or pseudoproline. The mechanical properties of these materials, determined via parallel plate rheology, were dependent on the polymer concentration, as was the hydrogel adhesive strength, which was determined by lap shear adhesive testing. In addition, these hydrogels were efficacious in closing ex vivo 4.1 mm central corneal lacerations: wounds closed with these hydrogel adhesives were able to withstand intraocular pressure values equivalent to, or in excess of, those obtained by closing the wounds with suturing.

Accuracy of a novel noninvasive transdermal continuous glucose monitor in critically ill patients.

Stress hyperglycemia and hypoglycemia are associated with increased morbidity and mortality in the critically ill. Intermittent, random blood glucose (BG) measurements can miss episodes of hyper- and hypoglycemia. The purpose of this study was to determine the accuracy of the Symphony® continuous glucose monitor (CGM) in critically ill cardiac surgery patients. Fifteen adult cardiac surgery patients were evaluated immediately postoperatively in the intensive care unit. Prelude® SkinPrep prepared the skin and a sensor was applied to 2 test sites on each subject to monitor interstitial fluid glucose. Reference BG was sampled at 30- to 60-minute intervals. The skin at the test sites was inspected for adverse effects. Accuracy of the retrospectively analyzed CGM data relative to reference BG values was determined using continuous glucose-error grid analysis (CG-EGA) and mean absolute relative difference (MARD). Using 570 Symphony CGM glucose readings paired with reference BG measurements, CG-EGA showed that 99.6% of the readings were within zones A and B. BG measurements ranged from 73 to 251 mg/dL. The MARD was 12.3%. No adverse device effects were reported. The Symphony CGM system is able to safely, continuously, and noninvasively monitor glucose in the transdermal interstitial fluid of cardiac surgery intensive care unit patients with accuracy similar to that reported with other CGM systems. Future versions of the system will need real-time data analysis, fast warm-up, and less frequent calibrations to be used in the clinical setting.

Polymer injection therapy to reverse remodel the papillary muscles: efficacy in reducing mitral regurgitation in a chronic ischemic model.

BACKGROUND: Ischemic mitral regurgitation (MR) results from displacement of the papillary muscles caused by ischemic ventricular distortion. Progressive left ventricular (LV) remodeling has challenged therapy. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced LV remodeling. METHODS AND RESULTS: Ten sheep underwent ligation of the circumflex branches to produce chronic ischemic MR over 8 weeks. PVA was injected into the myocardium underlying the infarcted papillary muscle. Two-dimensional and 3D echocardiograms and hemodynamic data were obtained before infarct (baseline), before PVA (chronic MR), and after PVA. PVA injection significantly decreased MR from moderate to severe to trace (MR vena contracta, 5.8±1.2 to1.8±1.3 mm; chronic MR to post-PVA stage; P=0.0003). This was associated with a decrease in infarcted papillary muscle-to-mitral annulus tethering distance (30.3±5.7 to 25.9±4.6 mm, P=0.02), tenting volume (1.8±0.7 to 1.4±0.5 mL, P=0.01), and leaflet closure area (8.8±1.3 cm(2)to 7.6±1.3 cm(2), P=0.004) from chronic MR to post-PVA stages. PVA was not associated with significant decreases in LV ejection fraction (41±3% versus 40±3%, P=NS), end-systolic elastance, τ (82±36 ms to 72±26, P=NS), or LV stiffness coefficient (0.05±0.04 to 0.03±0.01). CONCLUSIONS: PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving tethering and ischemic MR by correcting papillary muscle position.