Effects of lower alcohols on nanocomposite particles for inhalation prepared using O/W emulsion

BACKGROUND: Inhalable nanocomposite particles using O/W emulsions were studied. The effect of the composition of the dispersed phase on the nanoparticles in the nanocomposite particles was reported, however, the effect on the inhalation characteristics of nanocomposite particles has not been investigated. OBJECTIVE: The aim of this study was to study the effects of lower alcohols in the dispersed phase of O/W emulsions on inhalable nanocomposite particles. METHODS: Nanocomposite particles were prepared using a spray dryer from O/W emulsion. A mixed solution of dichloromethane and lower alcohols in which rifampicin (RFP) and poly(L-lactide-co-glycolide) were dissolved was used as a dispersed phase, and an aqueous solution in which arginine and leucine were dissolved was used as a continuous phase. RESULTS: We succeeded in preparing non-spherical nanocomposite particles with an average diameter of 9.01–10.91 μm. The results of the fine particle fraction (FPF) measurement showed that the higher the hydrophobicity of the lower alcohol mixed in the dispersed phase, the higher the FPF value. The FPF value of the nanocomposite particles was significantly increased by using ethanol and 1-propanol. CONCLUSIONS: The results were revealed that mixing 1-propanol with the dispersed phase increased the amount of RFP delivered to the lungs.

Predictive evaluation of multicomponent direct compress model tablets by integrating sphere UV-Vis spectroscopy and chemometrics

BACKGROUND: Control of the pharmaceutical manufacturing process and active pharmaceutical ingredients (API) is essential to product formulation and bioavailability. OBJECTIVE: The aim of this study is to predict tablet surface API concentration by chemometrics using integrating sphere UV-Vis spectroscopy, a non-destructive and contact-free measurement method. METHODS: Riboflavin, pyridoxine hydrochloride, dicalcium phosphate anhydrate, and magnesium stearate were mixed and ground with a mortar and pestle, and 100 mg samples were subjected to direct compression at a compaction pressure of 6 MPa at 7 mm diameter. The flat surface tablets were then analyzed by integrating sphere UV-Vis spectrometry. Standard normal variate (SNV) normalization and principal component analysis were applied to evaluate the measured spectral dataset. The spectral ranges were prepared at 300–800 nm and 500–700 nm with SNV normalization. Partial least squares (PLS) regression models were constructed to predict the API concentrations based on two previous datasets. RESULTS: The regression vector of constructed PLS regression models for each API was evaluated. API concentration prediction depends on riboflavin absorbance at 550 nm and the excipient dicalcium phosphate anhydrate. CONCLUSION: Integrating sphere UV-Vis spectrometry is a useful tool to process analytical technology.

Ultrasound simulation of blood with different red blood cell aggregations and concentrations

BACKGROUND: Considerable progress of ultrasound simulation on blood has enhanced the characterizing of red blood cell (RBC) aggregation. OBJECTIVE: A novel simulation method aims at modeling the blood with different RBC aggregations and concentrations is proposed. METHODS: The modeling process is as follows: (i) A three-dimensional scatterer model is first built by a mapping with a Hilbert space-filling curve from the one-dimensional scatterer distribution. (ii) To illustrate the relationship between the model parameters and the RBC aggregation level, a variety of blood samples are prepared and scanned to acquire their radiofrequency signals in-vitro. (iii) The model parameters are determined by matching the Nakagami-distribution characteristics of envelope signals simulated from the model with those measured from the blood samples. RESULTS: Nakagami metrics m estimated from 15 kinds of blood samples (hematocrits of 20%, 40%, 60% and plasma concentrations of 15%, 30%, 45%, 60%, 75%) are compared with metrics estimated by their corresponding models (each with different eligible parameters). Results show that for the three hematocrit levels, the mean and standard deviation of the root-mean-squared deviations of m are 0.27 ± 0.0026, 0.16 ± 0.0021, 0.12 ± 0.0018 respectively. CONCLUSION: The proposed simulation model provides a viable data source to evaluate the performance of the ultrasound-based methods for quantifying RBC aggregation.

Brushite bone cement containing polyethylene glycol for bone regeneration

BACKGROUND: Bone cements aid in bone regeneration; however, if the handling time is not well established for the material to harden, complications may arise. OBJECTIVE: This work investigates the effect of using polyethylene glycol (PEG) and characterize it in brushite bone cement in order to obtain desirable handling times as well as its regeneration in vivo to analyse if addition of this polymer may significantly modify its properties. METHODS: PEG 4000 was synthesised with wollastonite by phosphorization reaction in order to form brushite which was further cured by oven drying. They were further characterised and tested in vivo as tibial bone defect model using rabbits. RESULTS: Addition of PEG exhibited handling times of 60 min with a low increase in temperature when curing. Brushite phase of ∼71% was obtained after cement hardening with good compressive strength (25 MPa) and decent values of porosity (33%). In vivo presented that, at 40 days postoperatively, accelerated bone neoformation with partial consolidation at 30 days and total after 60 days when using bone cement. CONCLUSIONS: Addition of PEG does not disrupt the beneficial properties of the bone cement and can be a potential alternative for control the time-temperature profile of hardening these materials.

Role of miR-214 in biomaterial transplantation therapy for osteonecrosis

BACKGROUND: The effectiveness and availability of conservative therapies for osteonecrosis of the femoral head (ONFH) are limited. Transplantation of bone marrow mesenchymal stem cells (BMSCs) combined with Bio-Oss, which is a good bone scaffold biomaterial for cell proliferation and differentiation, is a new potential therapy. Of note, the expression of miRNAs was significantly modified in cells cultured with Bio-Oss, and MiR-214 was correlated positively with osteonecrosis. Furthermore, miR-214 was upregulated in cells exposed to Bio-Oss. OBJECTIVE: To investigate whether targeting miR-214 further improves the transplantation effect. METHODS: We treated BMSCs with agomiR-214 (a miR-214 agonist), antagomiR-214 (a miR-214 inhibitor), or vehicle, followed by their transplantation into ONFH model rats. RESULTS: Histological and histomorphometric data showed that bone formation was significantly increased in the experimental groups (Bio-Oss and BMSCs treated with antagomiR-214) compared with other groups. CONCLUSIONS: miR-214 participates in the inhibition of osteoblastic bone formation, and the inhibition of miR-214 to bone formation during transplantation therapy with Bio-Oss combined with BMSCs for ONFH.

In vivo comparison of the degradation and osteointegration properties of micro-arc oxidation—coated Mg–Sr and Mg–Ca alloy scaffolds

BACKGROUND: Magnesium (Mg) alloy have biodegradation and mechanical properties that are similar to those of human bone, making it a promising candidate material for inclusion in implantable medical devices. OBJECTIVE: The osteointegration effect of Mg alloy scaffolds with different corrosion rates were studied and evaluated in large bone defect models. METHOD: Mg–Sr and Mg–Ca alloy scaffolds with a 20-μm Micro-arc oxidation (MAO) coating were used to repair critical bone defects for subsequent assessment of each alloy’s degradation and osteointegration by X-ray, Micro-CT, fluorescence and histological examination. RESULTS: At 12 weeks post-implantation, each defect was found to be effectively reconstructed by either of the Mg alloys based on X-ray and Micro-CT images. The corrosion rate (CR) of each Mg alloy – as calculated based on micro-computed tomography information – demonstrated that the MAO coating could provide effective protection for only 4 weeks post-surgery. From weeks 8 to 12, the CR of the Mg–Ca alloy scaffold increased from 1.34 ± 0.23 mm/y to 1.57 ± 0.16 mm/y. In contrast, the CR of the Mg–Sr alloy scaffold decreased from 0.58 ± 0.14 mm/y to 0.54 ± 0.16 mm/y. However, fluorescence and histological examination revealed more mature, closely and regularly arranged newborn osteocytes at the Mg–Ca scaffold-fracture interface e from weeks 8 to 12 after surgery. RESULTS: The Mg–Sr scaffold was more corrosion resistant and the Mg–Ca scaffold yielded a better overall repair, which indicates that the CR of magnesium alloys matches the rate of new bone formation and is the key to repair bone defects as a bone substitute.

Comparison of polymerization stresses of dental resin composites evaluated by two indentation fracture methods

BACKGROUND: Polymerization stress is a major problem in dental resin composite restorations. Two indentation fracture methods can be applied to evaluate the stress, however, they often calculate different values. OBJECTIVE: To compare polymerization stresses of dental composites determined by the two methods. METHODS: Glass disks with a central hole were used. Two indentation fracture methods (Methods 1 and 2) were employed to determine the polymerization stresses of low-shrinkage and bulk-fill composites. Method 1: Cracks were made in the glass surface at 300 μm from the hole. The hole was filled with the composite. Polymerization stresses at 30 min after filling were calculated from the lengths of crack extension. Method 2: The hole was filled with the composite. Cracks were introduced in the glass at 1,000 μm from the hole at 30 min after the polymerization and the stresses were calculated from the crack lengths. Stresses at composite-glass bonded interface were calculated from the stress values obtained by the two methods. RESULTS: The bulk-fill composite generated the smallest interfacial stress, and Method 1 revealed lower values than Method 2. CONCLUSIONS: The composites yielded relatively small stresses. Method 1 calculated smaller stress values, possibly affected by the lower threshold stress intensity factor.

Experimental study on co-culture of DiI labeled rat bone marrow mesenchymal stem cells and polycaprolactone film in vitro to make a cell patch

BACKGROUND: In stem cell therapy, due to the lack of an effective carrier, a large number of transplanted stem cells are lost and die. Therefore, finding a suitable carrier has become a further direction of stem cell therapy. OBJECTIVE: In research on the co-culture of polycaprolactone (PCL) with 1,1′-Dioctadecyl-3,3,3′,3′- tetramethylindocarbocyanine perchlorate (DiI) labeled bone marrow mesenchymal stem cells (BMSCs), we observe the effect of materials on the growth and proliferation of DiI labeled stem cells, and the effect of DiI labeling on patch preparation, so as to find a kind of biomaterial suitable for the growth and proliferation of BMSCs, and find a suitable cell carrier for stem cell therapy of myocardial infarction and in vivo tracing. METHODS: Clean grade Sprague Dawley rats were selected as experimental objects, BMSCs were isolated and cultured, and the surface markers were identified by flow cytometry. After the BMSCs were cultured for 3 passages, the BMSCs were stained with DiI dye, and the BMSCs DiI and PCL biomaterial film were co-cultured. After 24 hours, the cell growth was observed under fluorescence microscope, and fixed for scanning under electron microscope. The cell proliferation was detected by CCK-8 at 1, 4, 7, 10 days of culture. The measurement data conforming to normal distribution are expressed in the form of mean ± standard deviation (X¯± s). One way ANOVA was used for comparison among groups, LSD analysis was used for pairwise comparison. The difference was statistically significant (P < 0.05). RESULTS: BMSCs were strongly positive for CD90, CD44H, but negative for CD11b/c, CD45. Under fluorescence microscope, BMSCs DiI showed red light, fusiform or polygonal. Under the scanning electron microscope, the cell patch formed by co-culture of PCL film and DiI-BMSCs had a large number of cells on the surface and normal cell state. CCK-8 assay showed that the OD value on the first day was 0.330 ± 0.025; The OD value was 0.620 ± 0.012 on the 4th day, 1.033 ± 0.144 on the 7th day and 1.223 ± 0.133 on the 10th day. There was significant difference among the time points (P < 0.05). CONCLUSIONS: The cell patch made of PCL film and DiI labeled BMSCs can survive and proliferate on the surface, so it can be used as a scaffold material for stem cell therapy in vivo.

Numerical investigation on the stability of human upper cervical spine (C1–C3)

BACKGROUND: The finite element method (FEM) is an efficient and powerful tool for studying human spine biomechanics. OBJECTIVE: In this study, a detailed asymmetric three-dimensional (3D) finite element (FE) model of the upper cervical spine was developed from the computed tomography (CT) scan data to analyze the effect of ligaments and facet joints on the stability of the upper cervical spine. METHODS: A 3D FE model was validated against data obtained from previously published works, which were performed in vitro and FE analysis of vertebrae under three types of loads, i.e. flexion/extension, axial rotation, and lateral bending. RESULTS: The results show that the range of motion of segment C1–C2 is more flexible than that of segment C2–C3. Moreover, the results from the FE model were used to compute stresses on the ligaments and facet joints of the upper cervical spine during physiological moments. CONCLUSION: The anterior longitudinal ligaments (ALL) and interspinous ligaments (ISL) are found to be the most active ligaments, and the maximum stress distribution is appear on the vertebra C3 superior facet surface under both extension and flexion moments.

Numerical simulation flow dynamics of an intracranial aneurysm

BACKGROUND: Computational fluid dynamics provides a new method for the study of the blood flow characteristics of the formation and development of intracranial aneurysms. OBJECTIVE: To compare blood flow characteristics between the healthy internal carotid artery and normal intracranial aneurysms. METHODS: The internal carotid arteries were simulated to obtain hemodynamic parameters in one patient. RESULTS: The internal carotid artery associated with aneurysm presents low wall shear stress, high oscillatory shear index, and high particle retention time compared with the normal internal carotid artery. CONCLUSIONS: There are differences in blood flow between the normal internal carotid artery and intracranial aneurysm. The vortex of the aneurysm will produce turbulence, indicating that it is unstable, which results in the growth and rupture of the aneurysm.