Fluxgate magnetorelaxometry: a new approach to study the release properties of hydrogel cylinders and microspheres.

Hydrogels are under investigation as long term delivery systems for biomacromolecules as active pharmaceutical ingredients. The release behavior of hydrogels can be tailored during the fabrication process. This study investigates the applicability of fluxgate magnetorelaxometry (MRX) as a tool to characterize the release properties of such long term drug delivery depots. MRX is based on the use of superparamagnetic core-shell nanoparticles as model substances. The feasibility of using superparamagnetic nanoparticles to study the degradation of and the associated release from hydrogel cylinders and hydrogel microspheres was a major point of interest. Gels prepared from two types of photo crosslinkable polymers based on modified hydroxyethylstarch, specifically hydroxyethyl starch-hydroxyethyl methacrylate (HES-HEMA) and hydroxyethyl starch-polyethylene glycol methacrylate (HES-P(EG)(6)MA), were analyzed. MRX analysis of the incorporated nanoparticles allowed to evaluate the influence of different crosslinking conditions during hydrogel production as well as to follow the increase in nanoparticle mobility as a result of hydrogel degradation during release studies. Conventional release studies with fluorescent markers (half-change method) were performed for comparison. MRX with superparamagnetic nanoparticles as model substances is a promising method to analyze pharmaceutically relevant processes such as the degradation of hydrogel drug carrier systems. In contrast to conventional release experiments MRX allows measurements in closed vials (reducing loss of sample and sampling errors), in opaque media and at low magnetic nanoparticle concentrations. Magnetic markers possess a better long-term stability than fluorescent ones and are thus also promising for the use in in vivo studies.

Echocardiographic prediction of patent ductus arteriosus in need of therapeutic intervention.

AIM: To evaluate the efficacy of various echocardiographic markers in predicting a patent ductus arteriosus (PDA) in need of treatment. METHODS: Forty-five preterm infants with a mean (SD) gestational age of 27.7 (1.9) weeks underwent echocardiography at a postnatal age of 24 ± 6 and 72 ± 6 h. Four echocardiographic markers were studied: ductus diameter, ductal flow Doppler curves, the left atrial to aortic root (LA/Ao) ratio and Doppler pixels representing ductal shunting. RESULTS: Twenty-eight infants had a PDA with a detectable left-to-right shunt. Of these, 12 (43%) were treated for a shunt through the PDA. Ductal diameter was the most accurate echocardiographic marker when it came to predicting a significant shunt, with a sensitivity of 89%, a specificity of 70%, a positive likelihood ratio of 2.97 and a negative likelihood ratio of 0.16 at the age of 72 h. The efficacy of the method at 72 h of age was 84%. The corresponding efficacy of the pulsatile Doppler curve was 72%, percentage of green colour pixels 63% and the LA/Ao ratio 53%. CONCLUSION: Ductus diameter appears to be the most important variable in determining the need for therapeutic intervention for PDA in preterm infants.

Fluxgate magnetorelaxometry for characterization of hydrogel polymerization kinetics and physical entrapment capacity.

Hydrogels have the potential for providing drug delivery systems with long release rates. The polymerization kinetics and the physical entrapment capacity of photo-cross-linked hydroxyethyl methacrylate hydroxyethylstarch hydrogels are investigated with a non-destructive method. For this purpose, superparamagnetic nanoparticles as replacements for biomolecules are used as probes. By analyzing their magnetic relaxation behavior, the amounts of physically entrapped and mobile nanoparticles can be determined. The hydrogels were loaded with five different concentrations of nanoparticles. Different methods of analysis of the relaxation curves and the influence of the microviscosity are discussed. This investigation allows one to optimize the UV light irradiation time and to determine the amount of physically entrapped nanoparticles in the hydrogel network. It was found that the polymerization kinetics is faster for decreasing nanoparticle concentration but not all nanoparticles can be physically entrapped in the network.

Giant-cell tumour of soft tissue in two Sprague-Dawley rats.

Two cases of soft tissue giant-cell tumours are reported in Sprague-Dawley rats. The lesions had the characteristic appearance of multinucleate tumour giant cells and were unassociated with bone. A search of the literature failed to reveal any previous report of this lesion in the rat.

Malignant phaeochromocytoma with widespread metastasis in the rat.

Malignant phaeochromocytomas occurring in the adrenals of 2 aged male rats are reported. The primary tumour was unilateral and had metastasized to the other adrenal, pancreas, liver, spleen, lung, kidney and bone marrow. Metastatic deposits were also seen in a co-existing pituitary tumour and in an islet cell carcinoma of the pancreas. The cells, although resembling normal medullary cells, were smaller and had sparse cytoplasm; the nuclei were generally hyperchromatic. The cells were arranged in nests and sometimes in a trabecular pattern. The presence of phaeochromocytomas with widespread metastasis is of interest since, in general, phaeochromocytomas of rats are not prone to metastasize. In addition, invasion into a pancreatic islet cell tumour and into a pituitary tumour was unusual.