Synthesis and characterization of paclitaxel-imprinted nanoparticles for recognition and controlled release of an anticancer drug

Imprinted nanoparticles as drug delivery carriers have been considered because owing to their cross-linked network, they act as the drug reservoir for controlled release. In this study, selective MIPs nanoparticles of paclitaxel (PTX) were successfully developed for application in the biological molecular recognition and in the design of new anticancer drug delivery systems. The MIPs nanoparticles prepared by miniemulsion polymerization technique using methacrylic acid (MAA) and methyl methacrylate as non-covalent functional monomer, ethylene glycol dimethacrylate and trimethylolpropane trimethacrylate (TRIM) as cross-linker agent, azobisisobutyronitrile as initiator, and hexadecane as hydrophobic agent. In order to prepare of MIP nanoparticles, the synthesis conditions and effective parameters, such as: cross-linker agent, different molar ratios of template–functional monomer–cross-linker agent, were investigated. In addition, the effect of different molar ratios of template and monomers on polymers binding and morphology were characterized. Structure and thermal properties of MIPs were confirmed by FT-IR spectroscopy and thermogravimetric analysis. Imprinted nanoparticles showed significant drug loading and encapsulation efficiency, 17.8 and 100 %, respectively. The particle size of MIP nanoparticles varies between 187 and 726 nm, according the SEM images and laser light scattering data. The imprinted nanoparticles showed satisfactory affinity (84 %) to PTX with a binding of 12 times higher than non-imprinted nanoparticles in biological samples when MAA and TRIM were used as functional and cross-linker monomer, respectively. Results from release experiments of MIPs showed a very slow and controlled release of PTX which would be helpful for sustained drug delivery.     

Dipyridamole recognition and controlled release by uniformly sized molecularly imprinted nanospheres

We used novel synthetic conditions of precipitation polymerization to obtain uniformly sized molecularly imprinted nanospheres of dipyridamole for application in the design of new drug delivery systems. In addition, the morphology, drug release, and binding properties of molecularly imprinted polymers (MIPs) were studied, and the effects of morphology on other properties were investigated. The MIPs prepared by acetonitrile/chloroform (19:1, v/v) were uniformly sized nanospheres with an average mean diameter of approximately 88 nm at a wetted state, 50 nm at a dry state, and a polydispersity index of 0.062. The imprinted nanospheres showed excellent binding properties and had 62.7% of template binding compared with 17.1% of its blank polymer. The imprinted nanospheres with 67.5 (mg template/of polymer) of binding capacity had better imprinting efficiency than the 50.5% of binding capacity shown by irregularly shaped MIP particles that were prepared by chloroform. The molecular binding abilities of imprinted nanospheres in human serum were evaluated by HPLC analysis (binding about 77% of dipyridamole). Results from release experiments of MIPs showed a very slow, controlled, and satisfactory release of dipyridamole. The loaded drug was released up to 99% in 17 days for nanospheres and 22 days for irregularly shaped particles.     

Preparation of nanocrystalline MgO by surfactant assisted precipitation method

Nanocrystalline magnesium oxide with high surface area was prepared by a simple precipitation method using pluronic P123 triblock copolymer (Poly (ethylene glycol)-block, Poly (propylene glycol)-block, Poly (ethylene glycol)) as surfactant and under refluxing conditions. The prepared samples were characterized by X-ray diffraction (XRD), N₂ adsorption (BET) and scanning and transmission electron microscopies (SEM and TEM). The obtained results revealed that the refluxing time and temperature and the molar ratio of surfactant to metal affect the structural properties of MgO, because of the changes in the rate and extent of P123 adsorption on the prepared samples. The results showed that the addition of surfactant is effective to prepare magnesium oxide with high surface area and affects the morphology of the prepared samples. With increasing the P123/MgO molar ratio to 0.05 the pore size distribution was shifted to larger size. The sample prepared with addition of surfactant showed a plate-like shape which was completely different with the morphology of the sample prepared without surfactant. The formation of nanoplate-like MgO was related to higher surface density of Mg ions on the (0 0 1) plane than that on the other planes of the Mg(OH)₂ crystal. The (0 0 1) plane would be blocked preferentially by the adsorbed P123 molecules during the growing process of Mg(OH)₂ nanoentities and the growth on the (0 0 1) plane would be markedly restricted, and the consequence is the generation of nanoplate-like MgO. In addition, increase in refluxing temperature and time increased the specific surface area of the prepared MgO samples.     

Tuning and optimization of structure and surface properties of thin and fine hydrophilic nanofibrous substrates through low-pressure heat-press treatment

The properties of electrospun nanofibrous membranes (ENMs), including pore size, surface roughness, and hydrophilicity, significantly affect crosslinking, thickness, and morphology of the polyamide selective layer formed on top of ENM substrate in thin film composite membranes, and, ultimately the performance of membranes. We produced polyamide 66 nanofiber layers with a thickness of 10 μm and a fiber diameter of 55 nm, considerably thinner and finer than usual ENM substrates. We then subjected this thin layer to post-production treatment using the efficient low-pressure heat-press (LPHP) method at a pressure of 3 kPa at three different temperatures and two different time intervals. It was found that the morphology of the nanofiber layer was preserved, and its structural characteristics, including pore structure, surface roughness, wettability, crystallinity, and specific surface area, were favorable with LPHP treatment. The optimal conditions were obtained with treatment at 190°C for 3600 s, in which the roughness of the nanofiber substrate decreased from 64 to 25 nm. Using these substrates offers new, less-explored opportunities for optimizing the LPHP treatment of the substrate. These substrates are proposed for a new generation of TFC membranes in a continuous production line, with the possibility of scaling up for pressure- and osmosis-driven membranes.     

Low-temperature synthesis of mesoporous nanocrystalline magnesium aluminate (MgAl2O4) spinel with high surface area using a novel modified sol-gel method

A simple, template-free and scalable modified sol-gel route was developed for the synthesis of mesoporous flake-like magnesium aluminate spinel (MgAl₂O₄) at low temperature (700 °C) with high surface area (281 m² g^?1). The obtained spinel materials were characterized by means of physicochemical techniques including X-ray diffraction, thermogravimetric analysis, scanning electron microscopy with energy-dispersive X-ray spectroscopy, transmission electron microscopy, Fourier transform infrared spectroscopy and N₂ adsorption-desorption analysis. The propylene oxide was used as gelation and pore forming agent in the sol-gel process. Different morphologies and sizes of flake were generated by the varied synthesis conditions. The result materials reveal that the textural properties of the MgAl₂O₄ product are strongly associated with the nature and amount of addictive solvent and calcination temperatures. It shows that the BET surface area decrease as the increase of calcination temperature and the optimal temperature of 700 °C result in the pure phase of MgAl₂O₄ spinel. This synthesis strategy offers a feasible approach for scalable fabrication of mixed metal oxides for various catalytic reactions or catalyst supports due to the large surface area.     

Lipoprotein(a) and inflammation in human coronary atheroma: association with the severity of clinical presentation

OBJECTIVES: The purpose of this study was the investigation of the in vivo role of lipoprotein(a) [Lp(a)] and inflammatory infiltrates in the human coronary atherosclerotic plaque and their correlation with the clinical syndrome of presentation. BACKGROUND: Lipoprotein(a) is an atherogenic and thrombogenic lipoprotein, and has been implicated in the pathogenesis of acute coronary syndromes. Lipoprotein(a) induces monocyte chemoattraction and smooth muscle cell activation in vitro. Macrophage infiltration is considered one of the mechanisms of plaque rupture. METHODS: This study of atherectomy specimens investigated the in vivo role of Lp(a) at different stages of the atherogenic process, and its relationship with macrophage infiltration. We examined coronary atheroma removed from 72 patients with stable or unstable angina. Specimens were stained with antibodies specific for Lp(a), macrophages (KP-1), and smooth muscle cells (alpha-actin). Morphometric analysis was used to quantify the plaque areas occupied by each of the three antigens, and their colocalization. RESULTS: All specimens had localized Lp(a) staining; the mean fractional area was 58.2%. Ninety percent of the macrophage areas colocalized with Lp(a) positive areas, whereas 31.3% of the smooth muscle cell areas colocalized with Lp(a) positive areas. Patients with unstable angina (n = 46) had specimens with larger mean plaque Lp(a) areas than specimens from stable angina patients (n = 26): 64.4% versus 47.7% (p = 0.004). Unstable angina patients with rest pain (n = 28) had greater mean plaque Lp(a) area than unstable angina patients with crescendo exertional pain (n = 18): 71.1% versus 52.4% (p < 0.001). Mean KP-1 area was 31.2% in unstable rest angina versus 18.3% in stable angina (p = 0.05); alpha-actin area was greater in stable (48.5%) and crescendo exertional angina (48.8%) than in rest angina (30.4%). The strongest correlation between plaque KP-1 and Lp(a) area was in unstable rest angina (r = 0.88, p < 0.001), and between alpha-actin and Lp(a) areas in the crescendo exertional angina (r = 0.62, p < 0.01). CONCLUSIONS: Lipoprotein(a) is ubiquitous in human coronary atheroma. It is detected in larger amounts in tissue from culprit lesions in patients with unstable compared to stable syndromes, and has significant colocalization with plaque macrophages. A correlation of plaque alpha-actin and Lp(a) area suggests a role of Lp(a) in plaque growth.     

Validation of the in vivo intravascular ultrasound measurement of in-stent neointimal hyperplasia volumes

OBJECTIVES: This study was undertaken to validate the in vivo intravascular ultrasound (IVUS) measurement of in-stent neointimal hyperplasia (IH) volumes. BACKGROUND: Because stents reduce restenosis compared to balloon angioplasty, stent use has increased significantly. As a result, in-stent restenosis is now an important clinical problem. Serial IVUS studies have shown that in-stent restenosis is secondary to intimal hyperplasia. To evaluate strategies to reduce in-stent restenosis, accurate measurement of in-stent neointimal tissue is important. METHODS: Using a porcine coronary artery model of in-stent restenosis, single Palmaz-Schatz stents were implanted into 16 animals with a stent:artery ratio of 1.3:1. Intravascular ultrasound imaging was performed at 1 month, immediately prior to animal sacrifice. In vivo IVUS and ex vivo histomorphometric measurements included stent, lumen and IH areas; IH volumes were calculated with Simpson's rule. RESULTS: Intravascular ultrasound measurements of IH (30.4+/-11.0 mm3) volumes correlated strongly with histomorphometric measurements (26.7+/-8.5 mm3, r=0.965, p < 0.0001). The difference between the IVUS and the histomorphometric measurements of IVUS volume was 4.1+/-2.7 mm3 or 15.8+/-11% (standard error of the estimate=0.7). Both histomorphometry and IVUS showed that IH was concentric and uniformly distributed over the length of the stent. Intravascular ultrasound detected neointimal thickening of < or =0.2 mm in 5 of 16 stents. Sample size calculations based on the IVUS measurement of IH volumes showed that 12 stented lesions/arm would be required to show a 50% reduction in IVUS-measured IH volume and 44 stented lesions/arm would be required to show a 25% reduction in IH volume. CONCLUSION: In vivo IVUS measurement of IH volumes correlated strongly with ex vivo histomorphometry. Using volumetric IVUS end points, small sample sizes should be necessary to demonstrate effectiveness of strategies to reduce in-stent restenosis.     

1.7 Volt, DC to 15 GHz Differential Amplifier with Constant Group Delay in InP-HBT Technology

10 dB gain–, 15 GHz-Bandwidth amplifier has been designed andfabricated in InP-HBT technology. Operation of the amplifier was achieved at1.7 V at total current consumption of 40 mA. The amplifier designed to havea Bessel-transfer-function has almost constant group delay up to 30 GHz.Pulse- and eye-diagram- measurements have been performed to verify largesignal operation. At 3.3 V, 24 dB gain and 10 GHz bandwidth was achieved.The 1dB compression point at 1.7 V supply voltage is measured at –10dBm output power.     

Action-Based Causal Reasoning

In this paper we present a causal theory based on aninterventionist conception of causality, i.e., a preference toselect causes among a set of actions which an agent has the abilityto perform or not to perform (free will). The most interestingproposals encountered in the literature, in nonmonotonic reasoning,all revolve around the ordered notion of similarity, abnormality,preference etc... but do not provide a full-fledgedsolution to the problem of the concrete definition of this order. Inour approach we relate the notion of action to norms (what isnormally the case when an action is undertaken, what is normally theoutcome of that action) and considering reasonable assumptions, weshow the existence and uniqueness of the set of voluntary causes foran observed effect (explanation problem). Moreover, the approach advocated in this paper handles ramifications correctly.