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.     

Fabrication of HAp–8YSZ composite layer on Ti/TiO2 nanoporous substrate by EPD/MAO method

Zirconia/Hydroxyapatite composites containing 20–50 wt.% 8YSZ were prepared on Ti/TiO₂ substrates by electrophoretic deposition (EPD)/micro-arc oxidation (MAO) process. Titania, as an inner layer, was grown on the Ti plates using MAO treatment in order to form a strong join between substrate and HAp. These composites were produced by EPD in ethanol containing ZrO₂/HAp particles at 50, 100 and 150 V in 1 min. As-prepared samples were sintered at 900, 1100 and 1300 °C. HAp, β-TCP, CaZrO₃ phases were identified using X-ray diffractometry analysis (XRD). Scanning electron microscopy (SEM) utilized to study the surface morphology indicated a crack free microstructure at 1300 °C.     

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.     

On the formulation design and rheological evaluations of pectin-based functional gels

In the current study, formulation design and development of a novel pectin-based functional gel were investigated. Amidated low methoxyl pectin (ALMP), high methoxyl pectin (HMP), sorbitol, inulin, rebaudioside-A, gardenia, phloridzin, quercetin, apple flavor, and calcium chloride (as its dihydrated salt) were selected as general ingredients. Response surface methodology was applied to design different formulations and to investigate on their experimental responses. The oscillatory tests were carried out in 2 stages with ALMP, HMP, sorbitol, and inulin as the variables of the 1st stage and ALMP and calcium chloride as the variables of the 2nd stage. Results of the 1st stage indicated relatively similar behaviors throughout the frequency range applied for all of the samples studied (true gels). However, magnitudes of the 5 rheological parameters of this study (storage modulus, loss modulus, loss tangent, complex modulus, and complex viscosity) were affected by different variables (ALMP, HMP, inulin, and sorbitol concentrations). Experimental results confirmed that sorbitol could be omitted from the formula while inulin and HMP could be used at their highest levels studied. At the 2nd stage, only 2 formulas indicated a strong gel behavior and other formulas showed typical behaviors of weaker gels or those of the concentrated solutions. At the conclusion of this study, a finished gelled product formula was suggested with the application of the best levels of the ingredients. The resultant gel was found to be set rapidly with no syneresis and showed a potential to be considered as a functional gelled dessert.     

Three dimensional static and dynamic analysis of thick functionally graded plates by the meshless local Petrov–Galerkin (MLPG) method

In this paper, three dimensional (3D) static and dynamic analysis of thick functionally graded plates based on the Meshless Local Petrov–Galerkin (MLPG) is presented. Using the kinematics of a three-dimensional continuum, the local weak form of the equilibrium equations is derived. A weak formulation for the set of governing equations is transformed into local integral equations on local sub-domains using a Heaviside step function as test function. In this case, governing equations corresponding to the stiffness matrix do not involve any domain integration or singular integrals. Nodal points are distributed in the 3D analyzed domain and each node is surrounded by a cubic sub-domain to which a local integral equation is applied. The meshless approximation based on the three-dimensional Moving Least-Square (MLS) is employed as shape function to approximate the field variable of scattered nodes in the problem domain. The Newmark time integration method is used to solve the system of coupled second-order ODEs. Effective material properties of the plate, made of two isotropic constituents with volume fractions varying only in the thickness direction, are computed using the Mori–Tanaka homogenization technique. Numerical examples for solving the static and dynamic response of elastic thick functionally graded plates are demonstrated. As a result, the distributions of the deflection and stresses through the plate thickness are presented for different material gradients and boundary conditions. The effects of the volume fractions of the constituents on the centroidal deflection are also investigated. The numerical efficiency of the proposed meshless method is illustrated by the comparison of results obtained from previous literatures.     

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.     

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.     

Fatty Acid Composition of Sheep Tail-Fats from Five Iranian Native Breeds

Fifteen fat samples provided from 5 sheep of 5 different Iranian native breeds were examined for their fatty acid composition by means of gaschromatography. Over 30 components could be detected in most samples. Fifteen fatty acids occurred in measurable amounts commonly higher than 0.1% up to 53.5% of the total. The saturated part consisted for the major of myristic (2.4–5.5%), pentadecanoic, (0.6–1.0%), palmitic (18.2–23.6%), heptadecanoic (0.9–2.3%), stearic (7.1–22.1%) and arachidic (0.1–0.3%) acids. Myristoleic (0.3–2.1%), palmitoleic (1.4–3.6%), oleic (39.6–53.5%), linoleic (2.1–3.7%) and linolenic (2.2–2.9%) acids were the main unsaturated fatty acids identified in this investigation. The differences in fatty acid composition of fats from sheep of various breeds were considerably high in stearic and oleic acids in some cases. The variation in fatty acid composition of fat samples obtained from different parts of a tail was insignificant in all 5 sheep examined. No conclusion could be made as to whether the above mentioned considerable differences in fatty acid composition of tail fats from various sheep are due to difference in their breed or due to other factors.