Evaluation of drug-eluting nanoparticle coating on magnesium alloy for development of next generation bioabsorbable cardiovascular stents.

Since the introduction of bioabsorbable magnesium alloys into cardiovascular stent technology, many researches have been conducted to improve these metallic scaffolds. Various coatings and different coating techniques, super plastic deformation techniques and synthesizing different Mg-based alloy are examples of such efforts. In this study, a magnesium based alloy (WE43) was coated with dexamethasone loaded polymeric nanoparticles via electrospraying method. Drug release behavior, drug inhibitory effects, surface properties and cell responses to the surface were evaluated. Drug release profile was investigated and compared to drug-loaded nanoparticle on stainless steel as a control. The inhibitory effects of the drug-loaded nanoparticle coatings on smooth muscle cells was evaluated via MTT assay. Endothelial cells response to the surface was investigated by SEM. The results showed that contact angle and roughness of the surface were 131° and 600-800 nm, respectively. Drug release studies showed a burst release less than 30% after 24 h which followed by nearly zero order release kinetic. MTT assay showed that SMCs viability decreased to 60% and 25% after 24 and 72 h, respectively. SEM images indicated proper adhesion and proliferation of endothelial cells on the surface. The findings suggest that nanoparticle-coated surfaces could effectively inhibit SMC proliferation meanwhile provide desirable surface features for adhesion and proliferation of endothelial cell on magnesium alloy based stents.

Assessment of structural, biological and drug release properties of electro-sprayed poly lactic acid-dexamethasone coating for biomedical applications.

The efficacy of an implant is highly depends on its coating characteristics mainly determined by polymer properties and coating technique. Electro-spraying is an inexpensive and versatile coating technique with various advantages for biomedical application. In this study, the efficacy of electro-sprayed (ES) poly lactic acid (PLA)-dexamethasone (DEX) coatings for medical implants was evaluated and compared with spin-coated samples as control. Structural properties of coatings were investigated using X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Confocal and scanning electron microscopy (SEM), contact angle measurement and nanoindentation tests were used to study surface properties. Coating degradation rate and drug release profile were studied for 40 days. Cell viability experiments were also performed on human endothelial (HUVEC) and smooth muscle cells (HUASMC) using MTT assay and SEM. XRD and DSC analysis showed electro-spraying significantly reduce PLA and DEX crystallinity. Surface studies showed ES coatings has significantly higher hydrophobicity and roughness with microbead-nanofiber morphology vs. micro-nanoporous structure of spin-coated samples. Initial burst release of DEX was 22% and 10% after 6 h and total release was 71% and 46% after 40 days for ES and spin-coated samples, respectively. HUVEC viability of ES samples was higher than spin-coated ones after 1 and 4 days. However, dexamethasone release profile reduced HUASMC proliferation in ES PLA-DEX samples in comparison to spin-coated after 1 and 3 days. In conclusion, in vitro results showed potential of ES PLA-DEX as a biocompatible and efficient anti-inflammatory coating with suitable drug release profile for future applications such as coronary drug eluting stents.

Comparative study of different polymeric coatings for the next-generation magnesium-based biodegradable stents.

Development of next-generation bioabsorbable stents based on magnesium alloys is gaining lots of attention. However, finding an appropriate coating in order to enhance its corrosion resistance along with preserving other requirements is still a challenge. In this study, three FDA-approved polymers, namely poly(lactic acid), polycaprolactone and poly(lactic-co-glycolic acid), have been investigated as potential coatings for magnesium-based stents to enhance their corrosion resistance, biocompatibility and haemocompatibility. Potentiodynamic and electrochemical impedance spectroscopy results demonstrated that PLA and PLGA coating performed better in improving corrosion resistance in comparison with uncoated and other coated samples. Although all coated and bare samples displayed desirable results of haemocompatibility assays, PLA-coated samples showed better outcome in terms of biocompatibility. The results revealed that PLA can be considered as a potential coating material to enhance the main characteristics of magnesium-based bioabsorbable stents.

Expression of UBE2Q2, a putative member of the ubiquitin-conjugating enzyme family in pediatric acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is a cancer of the white blood cells most commonly found in childhood with a peak incidence at 2-5 years of age. The ubiquitin degradation pathway facilitates degradation of damaged proteins and regulates the growth and stress response. This pathway is activated in various cancers, including ALL. It has been previously reported that the newly characterized human gene UBE2Q2, a putative member of the ubiquitin-conjugating enzyme family, is over-expressed in the tumor mass and invasive epithelium in head and neck squamous cell carcinoma and breast cancer. METHODS: Here, we have used quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to assess expression of the UBE2Q2 gene in bone marrow samples of 20 children with ALL. Whole blood samples of 20 normal children were used as control specimens.  RESULTS: RT-PCR revealed the expression of UBE2Q2 mRNA in 80% of the bone marrow samples from ALL patients as well as in 85% of leukemic normal peripheral blood cells. According to the results of quantitative RT-PCR, the levels of UBE2Q2 mRNA expression in the bone marrow cells of 11 out of the 20 children with ALL (55%) were significantly higher (> 2-47 fold) than those in blood cells of normal children. CONCLUSION: Our data suggest that the newly characterized human gene, UBE2Q2, may have implications for the pathogenesis of ALL and could be used for molecular diagnosis purposes in the future.

Expression levels of the BDNF gene and histone modifications around its promoters in the ventral tegmental area and locus ceruleus of rats during forced abstinence from morphine.

Brain-derived neurotrophic factor (BDNF) plays a role in mediating molecular, cellular, and behavioral adaptations underlying drug addiction. Here, we examined the influence of withdrawal from repeated morphine treatment on the expression of BDNF mRNA in the ventral tegmental area (VTA) and locus coeruleus (LC) of the rat brain. We also studied whether alternations in mRNA levels of BDNF in these tissues are associated with histone modifications around promoters II and III of the BDNF gene. Thus, chromatin immunoprecipitation (CHIP) and quantitative (q)-PCR were employed to assess acetylation of histone H3 at K9/K14 and trimethylation of histone H3 at K9. Results of qRT-PCR showed that levels of BDNF mRNA in both VTA and LC were significantly increased 7 days rather than 2 h or 24 h following the last injection of morphine. Consistently, CHIP and qPCR analysis revealed that on day 7 of morphine abstinence, both VTA and LC levels of histone methylation at BDNF promoters II and III of morphine treated rats were significantly lower than control animals. Morphine withdrawal caused only a significant increase in H3 acetylation at the promoter II in the LC. These data demonstrate the involvement of histone H3 methylation in the regulation of gene expression in the VTA and LC of rats during forced abstinence of morphine.

Effect of oral resveratrol on the BDNF gene expression in the hippocampus of the rat brain.

Resveratrol is a plant polyphenolic compound. Evidence indicates that resveratrol has beneficial effects against aging and neurodegenerative diseases. The goal of our study was in vivo examination of the effects of resveratrol on the abundance of mRNA encoding Brain Derived Neurotrophic Factor (BDNF) in the hippocampus of rat brain. Rats were administrated orally by different doses (2.5-20 mg/kg bwt) of resveratrol for 3, 10 and 30 days. Saline was used as control and 10% ethanol in saline was used as vehicle for resveratrol. Measurement of BDNF mRNA by Real-time RT-PCR showed that levels of the mRNA for BDNF were significantly and dose dependently elevated in the hippocampal tissues of rats. The findings suggest that the neuroprotective effects of resveratrol may be at least partly due to its inducing effects on the expression levels of the BDNF mRNA.