Formulation and evaluation of novel tableted chitosan microparticles for the controlled release of clozapine

Controlled release formulations of clozapine microparticulated tablets were prepared by using chitosan. Microparticles were characterized for particle size and size distribution. Microparticles were compressed into tablets using the directly compressible excipients. SEM photographs of the fractured part of the tablet revealed the presence of discrete particles in the tablets, suggesting that the system chosen is ideal for tableting. Drug release from the tableted microparticles exhibited an initial burst effect, but the release decreased with increasing extent of cross-linking. Tablets were coated with chitosan or cellulose acetate, which significantly lowered the initial burst effect when compared to uncoated tablets. Drug release from chitosan-coated tablets was slightly higher than the tablets coated with cellulose acetate. Tablets prepared were effective in delivering clozapine over a period of 12?h.     

Visual working memory and perception speed of 3- to 6-year-old children tested with a Matrix Film Battery Test

In this study the visual working memory (VWM) and perception speed of 60 children between the ages of three and six years were tested with an age-based, easy-to-handle Matrix Film Battery Test (reliability R?=?.71). It was thereby affirmed that the VWM is age dependent (correlation coefficient r?=?.66***) as expected. Furthermore, a significant gender effect was found (partial correlation coefficient r_p?=?.42***) indicating that boys generally have a better VWM: they are able to memorise more items and they can process visual information faster. Given that the test was repeated during a period of eight months, strong learning effects could be detected which show that the VWM can be trained and that the test itself is also a good training tool.     

Single vs multivessel treatment during primary angioplasty: results of the multicentre randomised HEpacoat™ for cuLPrit or multivessel stenting for Acute Myocardial Infarction (HELP AMI) Study

DESIGN: Prospective randomized, multicentre study. RATIONALE: Recanalisation of the culprit lesion is the main goal of primary angioplasty for acute myocardial infarction. With the exception of cardiogenic shock, staged procedures are performed in the presence of multivessel disease. The study hypothesis is that with modern non-thrombogenic stents (heparin coated) complete revascularization with multivessel treatment can be safely achieved during the primary angioplasty procedure with a lower need of subsequent revascularization procedures and at a lower cost. ENDPOINTS: PRIMARY: 12-month incidence of repeat revascularization (any revascularization, infarct related artery as well as non-infarct-related artery). SECONDARY: (1) in hospital repeat revascularization, reinfarction and death; (2) total hospital cost (including a 12 months follow-up period). METHODS: 69 patients with ST elevation Acute Myocardial Infarction (AMI), <12 hours after symptoms onset, undergoing primary angioplasty, with documented multivessel disease and both culprit lesion and 1 to 3 other lesions suitable for stent implantation. Unbalanced randomization between culprit lesion treatment only ( n??=?17) and complete multivessel treatment (n?=?52, with 71 additional lesions treated).RESULTS: The two groups were well balanced in terms of clinical characteristics, number of diseased vessels and angiographic characteristics of the culprit lesion. In the complete multivessel treatment group 2.36?±?0.64 lesions per patient were treated using 2.73?±?0.78 heparin coated stents (1.00 lesions and 1.29?±?0.61 stents in the culprit treatment group, bothp?<?0.001). The duration of the procedure increased from 53?±?21?min (culprit treatment group) to 69?±?32?min (p?=?0.032) and the amount of contrast used from 242?±?102?ml (culprit treatment group) to 341?± 163?ml (multivessel complete treatment),p?=?0.025. A similar low incidence of in-hospital major adverse cardiac events was observed in the 2 groups (0 and 3.8% in culprit and multivessel treatment groups,p?=?0.164). The increase in the incidence of new revascularisation in the culprit treatment group at 12 month follow-up was not significant (35 vs 17%,p?=?0.247) but was sufficient to compensate the initial higher in-hospital cost, with a similar 12 month hospital cost in the 2 groups (€22 330?±?€13 653 vs €20 382?±?€11 671,p?=?0.231).CONCLUSION: Multivessel treatment during primary PTCA was safe in this controlled trial. However, when only the culprit lesion was initially treated, the need for subsequent clinically driven revascularization remained low and no clinical or economical advantages were obtainable with a more aggressive initial approach. In clinical practice, a staged approach to multivessel treatment during primary angioplasty avoids to treat unnecessarily non clinically relevant lesions. (Int J Cardiovasc Intervent 2004; 6: 128-133)     

Subwavelength Etched Colloidal Monolayers: A Model System for Tunable Antireflective Coatings

Colloidal monolayers represent a versatile material class to fabricate nanostructures with high quality. The length scale of the nanostructured film is given by the size of the colloidal nanoparticles. Importantly, colloidal monolayers, though being of hexagonally close packed symmetry, still embody a high amount of free volume. This reduces the effective refractive index of thin colloidal monolayer films significantly. For particles and periodicities <200 nm, the heterogeneous layer can be approximated by an effective medium theory. The amount of free volume can be further fine‐tuned by a controlled size reduction of the constituting spheres, for instance by plasma etching. This can be utilized to realize an optimum refractive index for the application of colloidal monolayers as antireflective (AR) coatings. In contrast, previously reported >200 nm monolayers demonstrate distinct extinction peaks due to grating diffraction. Rational design by the use of differently sized particles further allows shifting the best performance across the visible spectrum. Colloidal monolayers, though representing single‐layer AR coatings, exhibit broadband AR properties and are ideally suited to demonstrate the influence of refractive index and layer thickness, independently.

     

学龄前儿童口腔中挥发性硫化物的检出情况及其相关因素

目的:了解学龄前儿童口腔中挥发性硫化物的检出情况,分析引起学龄前儿童口臭的主要相关因素,为儿童口臭和相关疾病的预防和治疗提供依据. 方法:对北京市某幼儿园170名4~6岁学龄前儿童口腔中挥发性硫化物( volatile sulfur compounds,VSC)含量和口腔健康状况进行检查,对儿童家长进行问卷调查,挥发性硫化物的检测使用便携式气相色谱仪OralChromaTM. 使用SPSS 13. 0软件包,进行VSC与口腔健康状况和行为等的单因素和多因素分析. 结果:单因素分析结果显示,检出口臭的儿童占全部受检人数的34. 4%. 女童口腔中硫化氢( hydro-gen sulfide,H2S)[(1.59 ±2.41) ng/10 mL]和VSC总量[(2.14 ±4.42) ng/10 mL]高于男童(P<0.05). 舌苔指数高的儿童的H2S[舌苔面积(1.68 ±2.48) ng/10 mL,舌苔厚度(2.18 ±2.69) ng/10 mL)和VSC总量[舌苔面积(2. 26 ± 4. 31) ng/10 mL,舌苔厚度(2. 41 ± 3. 02) ng/10 mL]高于舌苔指数低的儿童(P<0. 01). 简化软垢指数记分值≥2的位点数值与甲硫醇(methyl mercaptan,CH3SH)和二甲基硫[dimethyl sulfide,(CH3)2S]浓度呈正相关(P<0.01);母亲受教育程度在本科及以上的儿童口腔中H2S值[(1.19 ±1.62)ng/10 mL]显著低于母亲教育程度在本科以下的儿童(P<0. 01);甜食进食频率高的儿童H2S浓度[(1. 04 ± 1. 55) ng/10 mL]低于频率低的儿童(P<0. 01);有张口呼吸习惯的儿童CH3SH和(CH3)2S浓度[(0. 29 ± 1. 92) ng/10 mL,(0. 37 ± 2. 06) ng/10 mL]显著高于没有张口呼吸习惯的儿童(P<0. 05). Logistic多因素分析结果显示,舌苔指数高、母亲教育程度低的儿童VSC高于舌苔指数低和母亲教育程度高的儿童. 结论:学龄前儿童口臭检出率高,性别、舌苔指数、软垢指数、母亲教育程度、甜食进食频率、张口呼吸等因素是儿童口臭的相关影响因素,不同影响因素导致不同VSC成分的改变.     

Bioadhesive vaginal drug delivery of nystatin using a derivatized polymer: Development and characterization

Increasing incidence of resistance to azole antifungals has highlighted the importance of the use of alternative therapeutic agents such as nystatin for the treatment of vulvovaginal candidiasis. The aim of the present study was to develop and characterize locally acting, film formulation for the treatment of candidiasis using a derivatized natural polymer. Derivatization of natural polymer was carried out in order to introduce anionic character to an otherwise neutral polymer, so as to enhance its interaction with vaginal mucous membrane along with inheriting the biocompatibility and nonirritant characteristics of its parent polymer. A carboxymethyl derivative of fenugreek gum (CMFG) was prepared, and characterized by DSC, FTIR and X-ray diffraction studies. The derivatized gum was found to possess bioadhesive and film forming properties. A 3² factorial design was employed to formulate vaginal films and a response surface methodological approach was used to study the effect of formulation variables on film properties. Films containing 5% w/v polymer and 2% v/v glycerol exhibited optimum properties in vitro. The optimized drug loaded formulation was able to release 100% drug over a period of 5 h and followed Korsmeyer–Peppas kinetics. It was found to be non-irritant and nontoxic to vaginal mucosa and showed appropriate antifungal properties in vivo.     

Monitoring film coalescence from aqueous polymeric dispersions using atomic force microscopy: Surface topographic and nano-adhesion studies

The aim of the investigation was to develop the use of topographic and nano-adhesion atomic force microscopy(AFM) studies as a means of monitoring the coalescence of latex particles within films produced from a pharmaceutically relevant aqueous dispersion(Eudragit~?NE30 D). Films were prepared via spin coating and analysed using AFM, initially via tapping mode for topographic assessment followed by force-distance measurements which allowed assessment of site-specific adhesion. The results showed that colloidal particles were clearly observed topographically in freshly prepared samples, with coalescence detected on curing via the disappearance of discernible surface features and a decrease in roughness indices. The effects of temperature and humidity on film curing were also studied, with the former having the most pronounced effect. AFM force measurements showed that the variation in adhesive force reduced with increasing curing time, suggesting a novel method of quantifying the rate of film formation upon curing. It was concluded that the AFM methods outlined in this study may be used as a means of qualitatively and quantitatively monitoring the curing of pharmaceutical films as a function of time and other variables, thereby facilitating rational design of curing protocols.     

Grafting antibiofilm polymer hydrogel film onto catheter by SARA SI-ATRP

Abstract

Catheters are widely used and play an important role in medicine. However, catheter-associated infection is prevalent even under stringent sterile conditions. Biofilms are formed when bacteria populate the surfaces of catheters. This makes the biofilm resistant to antibiotics. Hence, it is imperative for there to be an inherently antifouling and anti-bacterial catheter to mitigate the formation of biofilm. This paper aims to outline the synthesis of non-leachable anti-biofilm and anti-bacterial cationic film coatings through direct polymerization using supplemental activator and reducing agent surface initiated atom transfer radical polymerization (SARA SI-ATRP). Three crosslinked cationic coatings comprising of Diallyl dimethyl ammonium chloride (DADMAC), or ε-poly-L-lysine HCl methacrylic acid (EPL-MA) together with a crosslinker (polyethylene glycol dimethacrylate, PEGDMA) were investigated. These non-leachable covalently linked coatings with DADMAC can achieve more than 2 log reduction (99.0%) with Methicillin-resistant Staphylococcus aureus (MRSA) and 1.25 log reduction (94.4%) with Vancomycin resistant Enterococcus (VRE) in in vitro studies.     

Persistent inhibition of Candida albicans biofilm and hyphae growth on titanium by graphene nanocoating

ObjectivesCandida albicanscolonizes biomaterial surfaces and are highly resistant to therapeutics. Graphene nanocoating on titanium compromises initial biofilm formation. However, its sustained antibiofilm potential is unknown. The objective of this study was to investigate the potential of graphene nanocoating to decrease long-term fungal biofilm development and hyphae growth on titanium.MethodsGraphene nanocoating was deposited twice (TiGD) or five times (TiGV) on grade 4 titanium with vacuum assisted technique and characterized with Raman spectroscopy and atomic force microscope. The biofilm formation and hyphae growth of C. albicans was monitored for seven days by CFU, XTT, confocal, mean cell density and scanning electronic microscopy (SEM). Uncoated titanium was the Control. All tests had three independent biological samples and were performed in independent triplicates. Data was analyzed with one- or two-way ANOVA and Tukey's HSD (α = 0.05).ResultsBoth TiGD and TiGV presented less biofilms at all times points compared with Control. The confocal and SEM images revealed few adhered cells on graphene coated samples, absence of hyphae and no features of a mature biofilm architecture. The increase in number of layers of graphene nanocoating did not improve its antibiofilm potential.SignificanceThe graphene nanocoating exerted a long-term persistent inhibitory effect on the biofilm formation on titanium. The fewer cells that were able to attach on graphene coated titanium were scattered and unable to form a mature biofilm with hyphae elements. The findings open opportunities to prevent microbial attachment and proliferation on implantable materials without the use of antibiotics.