Astrocyte swelling in hepatic encephalopathy: molecular perspective of cytotoxic edema

Metabolic Brain Disease - Hepatic encephalopathy (HE) may occur in patients with liver failure. The most critical pathophysiologic mechanism of HE is cerebral edema following systemic...     

Evaluation of Bone Mineral Status in Adolescent Idiopathic Scoliosis

Background

Several reports have suggested low bone mineral density (BMD) in patients with adolescent idiopathic scoliosis (AIS). We determined bone mineral status in patients with AIS to evaluate the effect of brace treatment on BMD.

Methods

BMD was measured in 46 patients (mean age, 17.8 ± 4.9 years) with AIS (17 with brace and 29 without brace) by dual-energy X-ray absorptiometry scan and compared the results to an age-matched (mean age, 16.6 ± 3.9 years) control group (n = 54).

Results

The AIS group had significantly lower bone mass at the lumbar spine (Z-score, -1.500 vs. -0.832) and hip (Z-score, -1.221 vs. -0.754) except at the femoral neck. No difference in BMD was found between patients with AIS who used a brace and those who did not.

Conclusions

The results confirmed that BMD was low in AIS patients and it was not affected by brace treatment.     

The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium

Glucagon like peptide-1 (GLP-1) is an incretin hormone that is in the pipeline for type 2 diabetes mellitus (T2DM) therapy. However, oral administration of GLP-1 is hindered by the harsh conditions of the gastrointestinal tract and poor bioavailability. In this study, three nanosystems composed by three different biomaterials (poly(lactide-co-glycolide) polymer (PLGA), Witepsol E85 lipid (solid lipid nanoparticles, SLN) and porous silicon (PSi) were developed and loaded with GLP-1 to study their permeability in vitro. All the nanoparticles presented a size of approximately 200 nm. The nanoparticles' interaction with the mucus and the intestinal cells were enhanced after coating with chitosan (CS). PSi nanosystems presented the best association efficiency (AE) and loading degree (LD), even though a high AE was also observed for PLGA nanoparticles and SLN. Among all the nanosystems, PLGA and PSi were the only nanoparticles able to sustain the release of GLP-1 in biological fluids when coated with CS. This characteristic was also maintained when the nanosystems were in contact with the intestinal Caco-2 and HT29-MTX cell monolayers. The CS-coated PSi nanoparticles showed the highest GLP-1 permeation across the intestinal in vitro models. In conclusion, PLGA + CS and PSi + CS are promising nanocarriers for the oral delivery of GLP-1.     

Augmented cellular trafficking and endosomal escape of porous silicon nanoparticles via zwitterionic bilayer polymer surface engineering

The development of a stable vehicle with low toxicity, high cellular internalization, efficient endosomal escape, and optimal drug release profile is a key bottleneck in nanomedicine. To overcome all these problems, we have developed a successful layer-by-layer method to covalently conjugate polyethyleneimine (PEI) and poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface of undecylenic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs), forming a bilayer zwitterionic nanocomposite containing free positive charge groups of hyper-branched PEI disguised by the PMVE-MA polymer. The surface smoothness, charge and hydrophilicity of the developed NPs considerably improved the colloidal and plasma stabilities via enhanced suspensibility and charge repulsion. Furthermore, despite the surface negative charge of the bilayer polymer-conjugated NPs, the cellular trafficking and endosomal escape were significantly increased in both MDA-MB-231 and MCF-7 breast cancer cells. Remarkably, we also showed that the conjugation of surface free amine groups of the highly toxic UnTHCPSi-PEI (Un-P) NPs to the carboxylic groups of PMVE-MA renders acceptable safety features to the system and preserves the endosomal escape properties via proton sponge mechanism of the free available amine groups located inside the hyper-branched PEI layer. Moreover, the double layer protection not only controlled the aggregation of the NPs and reduced the toxicity, but also sustained the drug release of an anticancer drug, methotrexate, with further improved cytotoxicity profile of the drug-loaded particles. These results provide a proof-of-concept evidence that such zwitterionic polymer-based PSi nanocomposites can be extensively used as a promising candidate for cytosolic drug delivery.