In vitro dissolution methods for hydrophilic and hydrophobic porous silicon microparticles

Porous silicon (PSi) is an innovative inorganic material that has been recently developed for various drug delivery systems. For example, hydrophilic and hydrophobic PSi microparticles have been utilized to improve the dissolution rate of poorly soluble drugs and to sustain peptide delivery. Previously, the well-plate method has been demonstrated to be a suitable in vitro dissolution method for hydrophilic PSi particles but it was not applicable to poorly wetting hydrophobic thermally hydrocarbonized PSi (THCPSi) particles. In this work, three different in vitro dissolution techniques, namely centrifuge, USP Apparatus 1 (basket) and well-plate methods were compared by using hydrophilic thermally carbonized PSi (TCPSi) microparticles loaded with poorly soluble ibuprofen or freely soluble antipyrine. All the methods showed a fast and complete or nearly complete release of both model compounds from the TCPSi microparticles indicating that all methods described in vitro dissolution equally. Based on these results, the centrifuge method was chosen to study the release of a peptide (ghrelin antagonist) from the THCPSi microparticles since it requires small sample amounts and achieves good particle suspendability. Sustained peptide release from the THCPSi microparticles was observed, which is in agreement with an earlier in vivo study. In conclusion, the centrifuge method was demonstrated to be a suitable tool for the evaluation of drug release from hydrophobic THCPSi particles, and the sustained peptide release from THCPSi microparticles was detected

Radiation-induced accelerated aging of the brain vasculature in young adult survivors of childhood brain tumors

Background. Cranial radiotherapy may damage the cerebral vasculature. The aim of this study was to understand the prevalence and risk factors of cerebrovascular disease (CVD) and white matter hyperintensities (WMHs) in childhood brain tumors (CBT) survivors treated with radiotherapy.Methods. Seventy CBT survivors who received radiotherapy were enrolled in a cross-sectional study at a median 20 years after radiotherapy cessation. The prevalence of and risk factors for CVD were investigated using MRI, MRA, and laboratory testing. Tumors, their treatment, and stroke-related data were retrieved from patients' files.Results. Forty-four individuals (63%) had CVD at a median age of 27 years (range, 16-43 years). The prevalence rates at 20 years for CVD, small-vessel disease, and large-vessel disease were 52%, 38%, and 16%, respectively. Ischemic infarcts were diagnosed in 6 survivors, and cerebral hemorrhage in 2. Lacunar infarcts were present in 7, periventricular or deep WMHs in 34 (49%), and mineralizing microangiopathy in 21 (30%) survivors. Multiple pathologies were detected in 44% of the participants, and most lesions were located in a high-dose radiation area. Higher blood pressure was associated with CVD and a presence of WMHs. Higher cholesterol levels increased the risk of ischemic infarcts and WMHs, and lower levels of high-density lipoprotein and higher waist circumference increased the risk of lacunar infarcts.Conclusions. Treating CBTs with radiotherapy increases the risk of early CVD and WMHs in young adult survivors. These results suggest an urgent need for investigating CVD prevention in CBT patients.</div

Imaging the Impact of Prenatal Alcohol Exposure on the Structure of the Developing Human Brain

Prenatal alcohol exposure has numerous effects on the developing brain, including damage to selective brain structure. We review structural magnetic resonance imaging (MRI) studies of brain abnormalities in subjects prenatally exposed to alcohol. The most common findings include reduced brain volume and malformations of the corpus callosum. Advanced methods have been able to detect shape, thickness and displacement changes throughout multiple brain regions. The teratogenic effects of alcohol appear to be widespread, affecting almost the entire brain. The only region that appears to be relatively spared is the occipital lobe. More recent studies have linked cognition to the underlying brain structure in alcohol-exposed subjects, and several report patterns in the severity of brain damage as it relates to facial dysmorphology or to extent of alcohol exposure. Future studies exploring relationships between brain structure, cognitive measures, dysmorphology, age, and other variables will be valuable for further comprehending the vast effects of prenatal alcohol exposure and for evaluating possible interventions