急性冠脉综合征患者D31阳性CD42阴性内皮微粒的检测及其临床意义

目的 研究血浆CD31阳性CD42阴性的细胞微粒（CD-31 CD-42EMP）能否作为急性冠状动脉综合征患者危险程度的标志物.方法 收集62例急性冠脉综合征和62例稳定型冠心病患者及62例健康志愿者的血浆,用流式细胞术测定CD＋31 CD-42EMP水平,同时测定血浆超敏C-反应蛋白的水平.结果 与健康志愿者组比较,稳定型冠心病组患者CD＋31 CD-42EMP水平和超敏C-反应蛋白的水平明显升高,差异有显著性;与稳定型冠心病组患者及健康志愿者组比较,急性冠脉综合征组患者的CD＋31 CD-42EMP水平和超敏C-反应蛋白的水平明显升高,差异具有显著性.结论 CD＋31 CD-42EMP水平能作为急性冠脉综合征危险程度的标志物,且与超敏C-反应蛋白的水平有明显相关性.     

Layered lipid microcapsules for mesalazine delayed-release in children

The goal was to make available a delayed-release dosage form of mesalazine to be dispersed in water to facilitate swallowing in adults and children. Mesalazine microparticles containing carnauba wax were prepared by spray-congealing technique. A second step of spray-congealing of carnauba microparticles dispersed in liquefied stearic acid gave rise to mesalazine lipid microcapsules in which several carnauba microparticles remained embedded as cores in a reservoir structure. In order to favor their water dispersion, the lipid microcapsules were dry coated by tumbling them with different ratios of mannitol/lecithin microparticles prepared by spray-drying. Release rate measurements showed a delayed-release behavior, in particular a pH-dependence with less than 10% of drug released in acidic medium and complete release in phosphate buffer pH 7.4 in 4-5h. The layering with hydrophilic excipient microparticles allowed manufacturing of a pH-dependent dosage form suitable for extemporaneous oral use in adults and children.     

Sustained release and pharmacologic evaluation of human glucagon-like peptide-1 and liraglutide from polymeric microparticles

Abstract

The GLP1-receptor agonists exert regulatory key roles in diabetes, obesity and related complications. Here we aimed to develop polymeric microparticles loaded with homologous human GLP1 (7-37) or the analogue liraglutide. Peptide-loaded microparticles were prepared by a double emulsion and solvent evaporation process with a set of eight polymers based on lactide (PLA) or lactide-glycolide (PLGA), and evaluated for particle-size distribution, morphology, in vitro release and pharmacologic activity in mice. The resulting microparticles showed size distribution of about 30–50?μm. The in vitro kinetic release assays showed a sustained release of the peptides extending up to 30–40?days. In vivo evaluation in Swiss male mice revealed a similar extension of glycemic and body weight gain modulation for up to 25?days after a single subcutaneous administration of either hGLP1-microparticles or liraglutide-microparticles. Microparticles-loaded hGLP1 shows equivalent in vivo pharmacologic activity to the microparticles-loaded liraglutide.     

Magnetic alginate microspheres: system for the position controlled delivery of nerve growth factor

The use of polymeric carriers containing dispersed magnetic nanocrystalline particles for targeted delivery of drugs in clinical practice has attracted the interest of the scientific community. In this paper a system comprised of alginate microparticles with a core of magnetite and carrying nerve growth factor (NGF) is described. The magnetic properties of these microspheres, typical of superparamagnetic materials, allow precise and controlled delivery to the intended tissue environment. Experiments carried out on PC12 cells with magnetic alginate microspheres loaded with NGF have confirmed the induction of cell differentiation which is strongly dependent on the distance from the microsphere cluster. In addition, finite element modelling (FEM) of the release profile from the microspheres in culture, indicated the possibility of creating defined and predictable NGF gradients from the loaded microspheres. These observations on the carriage and release of growth factors by the proposed microparticles open new therapeutic options for both neuronal regeneration and of the development of effective neuronal interfaces.     

Impact of weight reduction on production of platelet-derived microparticles and fibrinolytic parameters in obesity

INTRODUCTION: Generation of platelet-derived microparticle (PMP) is implicated in cardiovascular disease (CVD). However, the influence of adiposity and weight reduction on PMP generation remains to be fully elucidated. We compared PMP generation and fibrinolytic parameters between 49 non-diabetic obese (obese group) and 37 age-matched non-obese subjects (control group), and compared the effects of weight reduction on the parameters between a 12-week calorie restricted diet and diet with aerobic exercise in obese subjects. MATERIALS AND METHODS: PMP, plasma levels of plasminogen activator inhibitor-1 (PAI-1) activity and tissue-type plasminogen activator (t-PA) antigen were measured before and after intervention. RESULTS: Before intervention, PMP, PAI-1 activity and t-PA antigen values were elevated in the obese group compared with the control group. In all 86 subjects of both groups, these three parameters correlated with body mass index, waist circumference and fat tissue mass. There was a positive correlation between plasma levels of fibrinolytic parameters and visceral fat area (VFA). PMP values correlated with subcutaneous fat area (SFA). The intervention significantly reduced PMP, PAI-1 activity and t-PA antigen levels. There was a significant correlation between percentages of changes in PMP values and those in BMI, fat tissue mass and VFA in the obese group. No additional effect of exercise on PMP or fibrinolytic parameters was observed. CONCLUSIONS: Overproduction of PMP and fibrinolytic abnormalities may be associated with excessive adipose tissue. Weight reduction by either calorie restriction with or without exercise improves fibrinolytic abnormalities and PMP overproduction, probably through reduction of adipose tissue.     

Evaluation of solid lipid microparticles produced by spray congealing for topical application of econazole nitrate

Objectives The aims of this study were to evaluate the suitability of the spray congealing technique to produce solid lipid microparticles (SLMs) for topical administration and to study the skin permeation of a drug from SLMs compared with solid lipid nanoparticles (SLNs). Methods Econazole nitrate was used as model drug and Precirol ATO 5 as the lipidic carrier. SLMs and SLNs were both prepared at 5: 1, 10: 1 and 12.5: 1 lipid: drug weight ratios and characterised in terms of particle size, morphology, encapsulation efficiency and chemical analysis of the particle surface. SLMs and SLNs were also incorporated into HPMC K 100M hydrogels for ex‐vivo drug permeation tests using porcine epidermis. Key findings SLMs had particle sizes of 18–45 μm, while SLNs showed a mean diameter of 130–270 nm. The encapsulation efficiency was 80–100%. Permeation profiles of econazole nitrate were influenced by both particle size (significant difference until 9 h) and the amount of lipid. Conclusions The results confirm the usefulness of SLNs as carriers for topical administration and suggest the potential of SLMs for the delivery of drugs to the skin.     

Prospective randomized controlled study of a Chinese herbal medicine compound Tangzu Yuyang Ointment for chronic diabetic foot ulcers: a preliminary report

Aim of the study

The purpose of this study was to evaluate the efficacy and safety of a topical Chinese herbal medicine (CHM) compound Tangzu Yuyang Ointment (TYO) for treatment of chronic diabetic foot ulcers.

Materials and methods

This multi-center, prospective, randomized, controlled and add-on clinical trial was conducted at seven centers in the China mainland. Fifty-seven patients with chronic diabetic foot ulcers of Wagner's ulcer grade 1-3 were enrolled in this study. Patients who were randomly assigned to the control group (n = 28) received standard wound therapy (SWT), whereas those randomized to the treatment group (n = 28) received SWT plus topical TYO. Only 48 patients who finished 24 weeks of observations were entered for data analysis.

Results

The TYO and SWT groups were comparable for baseline characteristics. Ulcer improvement was 79.2% in the TYO group and 41.7% in the SWT group (P = 0.017) at 12 weeks, and 91.7% vs. 62.5% (P = 0.036) at 24 weeks. The number of ulcers that were completely healed at 4, 12 and 24 weeks was similar in both groups, as were the numbers of adverse events. Healing time was 96 ± 56 days (n = 19) in the TYO group and 75 ± 53 days (n = 14) in the SWT group (P = 0.271).

Conclusion

TYO plus SWT is more effective than SWT in the management of chronic diabetic foot ulcers and has few side-effects.     

Dexamethasone-containing biodegradable superparamagnetic microparticles for intra-articular administration: Physicochemical and magnetic properties, in vitro and in vivo drug release

Compared with traditional drug solutions or suspensions, polymeric microparticles represent a valuable means to achieve controlled and prolonged drug delivery into joints, but still suffer from the drawback of limited retention duration in the articular cavity. In this study, our aim was to prepare and characterize magnetic biodegradable microparticles containing dexamethasone acetate (DXM) for intra-articular administration. The superparamagnetic properties, which result from the encapsulation of superparamagnetic iron oxide nanoparticles (SPIONs), allow for microparticle retention with an external magnetic field, thus possibly reducing their clearance from the joint. Two molecular weights of poly(lactic-co-glycolic acid) (PLGA) were used, 12 and 19 kDa. The prepared batches were similar in size (around 10 μm), inner morphology, surface morphology, charge (neutral) and superparamagnetic behaviour. The SPION distribution in the microparticles assessed by TEM indicates a homogeneous distribution and the absence of aggregation, an important factor for preserving superparamagnetic properties. DXM release profiles were shown to be quite similar in vitro (ca. 6 days) and in vivo, using a mouse dorsal air pouch model (ca. 5 days).     

Composite microparticles with in vivo reduction of the burst release effect

The aim of this study was to develop microparticles containing nanoparticles (composite microparticles) for prolonged drug delivery with reduced burst effect in vitro and in vivo. Such composite microparticles were prepared with hydrophobic and biodegradable polymers [poly(ε-caprolactone), poly(lactic-co-glycolic) acid]. Ibuprofen was chosen as the model drug, and microparticles were prepared by the extraction technique with ethyl acetate as the solvent. Nanoparticles and microparticles and an ibuprofen solution (Pedea^®) were administered subcutaneously at the dose of 1 mg of ibuprofen per kg to overnight-fasted rats (male Wistar). Composite microparticles showed prolonged ibuprofen release and less burst effect when compared to simple microparticles (without nanoparticles inside) or nanoparticles both in vitro (PBS buffer) and in vivo. Moreover, ibuprofen was still detected in the plasma after 96 h with composite microparticles. Consequently, it has been demonstrated that composite microparticles were able to reduce burst release and prolong the release of ibuprofen for a long period of time.     

Towards More Realistic In Vitro Release Measurement Techniques for Biodegradable Microparticles

Purpose  To better understand the importance of the environmental conditions for drug release from biodegradable microparticles allowing for the development of more appropriate in vitro release measurement techniques. Methods  Propranolol HCl diffusion in various agarose gels was characterized by NMR and UV analysis. Fick’s law was used to theoretically predict the mass transport kinetics. Drug release from PLGA-based microparticles in such agarose gels was compared to that measured in agitated bulk fluids (“standard” method). Results  NMR analysis revealed that the drug diffusivity was almost independent of the hydrogel concentration, despite of the significant differences in the systems’ mechanical properties. This is due to the small size of the drug molecules/ions with respect to the hydrogel mesh size. Interestingly, the theoretically predicted drug concentration-distance-profiles could be confirmed by independent experiments. Most important from a practical point of view, significant differences in the release rates from the same batch of PLGA-based microparticles into a well agitated bulk fluid versus a semi-solid agarose gel were observed. Conclusion  Great care must be taken when defining the in vitro conditions for drug release measurements from biodegradable microparticles. The obtained new insight can help facilitating the development of more appropriate in vitro release testing procedures.