Elucidating the role of hyaluronic acid in the structure and morphology of calcium oxalate crystals

Recent surge in reports describing new additives that inhibiting the growth and nucleation of calcium oxalate (CaOx), the most common component of renal calculi or kidney stones, have rekindled interest in CaOx crystallization. In this in vitro study, the effect of hyaluronic acid (HA), a protein commonly found in urine, on the morphology and phase of the CaOx crystals is investigated. CaOx crystals were crystallized at pH 5.8 and 37 °C with a [Ca²⁺]:[C₂O₄^2-] ratio of 20:1, which is close to physiological conditions, in aqueous solution and artificial urine media. The obtained crystals were characterized structurally, morphologically and in terms of their surface charge. The crystals precipitated in aqueous solution without the HA additive were pure phase calcium oxalate monohydrate (COM) crystals with typical hexagonal morphology. The addition of HA partially promotes the transformation of COM into calcium oxalate dihydrate (COD) in aqueous solution. However, the only solid phase to form in artificial urine media with and without HA was identified as COD with tetragonal bipyramidal morphology. The results of this investigation will contribute to the understanding of the role HA plays on the morphology, structure, and thermal characteristics of CaOx and ultimately facilitate the development of effective treatments for kidney stones.     

Bilayered HA/CS/PEGDA hydrogel with good biocompatibility and self-healing property for potential application in osteochondral defect repair

The fabrication of osteochondral tissue engineering scaffolds comprised of different layers is a big challenge. Herein, bilayers comprised of double network hydrogels with or without nano hydroxyapatite (HAp) were developed by exploiting the radical reaction of poly(ethylene glycol) diacrylate (PEGDA) and the Schiff-base reaction of N-carboxyethyl chitosan (CEC) and oxidized hyaluronic acid sodium (OHA) for osteochondral tissue engineering. The bilayered osteochondral scaffold was successfully fabricated based on the superior self-healing property of both hydrogels and evaluated by scanning electron microscopy, macroscopic observation and mechanical measurements. In addition, the hydrogels exhibited good biocompatibility as demonstrated by the in vitro cytotoxicity and in vivo implantation tests. The results indicated that the bilayered hydrogel had great potential for application in osteochondral tissue engineering.     

An in vitro evaluation of fenugreek mucilage as a potential excipient for oral controlled-release matrix tablet

A polysaccharide mucilage derived from the seeds of fenugreek, Trigonella foenum-graceum L (family Fabaceae) was investigated for use in matrix formulations containing propranolol hydrochloride. Methocel^® hypomellose K4M was used as a standard controlled release polymer for comparison purposes. In this study the effect of lactose on the release behaviour of propranolol hydrochloride from matrices formulated to contain the fenugreek mucilage also was investigated. An increase in concentration of the mucilage in matrices resulted in a reduction in the release rate of propranolol hydrochloride comparable to that observed with hypomellose matrices. The rate of release of propranolol hydrochloride from fenugreek mucilage matrices was mainly controlled by the drug:mucilage ratio. However, the mechanism of release from matrices containing drug:mucilage ratios of 1:1, 1:1.25, 1:1.5, and 1:2 remained the same. The kinetics of release, utilising the release exponent n, showed that the values of n were between 0.46-0.57 indicating that the release from fenugreek mucilage matrices was predominantly by diffusion. The presence of lactose in matrices containing mucilage increased the release rate of propranolol hydrochloride. This is due to a reduction in tortuoisity and increased pore size of channels caused by lactose through which propranolol diffuses and therefore diffusion of water into the tablet is facilitated.     

Combined site-specific release retardant mini-matrix tablets (C-SSRRMT) for extended oral delivery of dexketoprofen trometamol: in vitro evaluation and single versus multiple doses pharmacokinetic study in human volunteers

Abstract

Development of extended release oral formulations of dexketoprofen trometamol (DT), a rapidly eliminated drug with high solubility, poses a great challenge especially when a portion of the dose is to be absorbed from the colon. In this study, site-specific release-retardant mini-matrix tablets (SSRRMTs) were developed and functionally coated with pH-responsive materials to achieve a site-specific delivery of DT at the duodenojejunal (DSRRMT) and ileocecal (ISRRMT) regions. Stomach-specific coated mini-tablets (SSCMTs) were manufactured for immediate release of about 16% of the daily dose of DT in the stomach. The SSCMT, DSRRMT, and ISRRMT were combined into a solid dosage form (C-SSRRMT tablets or capsules) to achieve the required linear release profile for once daily administration of DT. The SSRRMT and C-SSRRMT formulations were evaluated for the physical properties, in vitro-disintegration and in vitro dissolution and proved to be consistent with the pharmacopeial specifications. The in vitro release profiles of both C-SSRRMT tablets and capsules showed a constant release rate of about 6?mg/h and were similar to that of the theoretical target linear release profile. The pharmacokinetic study using human volunteers showed the bioequivalence of a single oral dose of C-SSRRMT capsules compared to three-successive oral doses of the immediate release market tablets with less ups and downs in the drug levels. The C-SSRRMT capsules formulation, may therefore, constitute an advance in the extended oral delivery of DT without the lack of efficacy and the adverse events frequently encountered in multiple daily dosing of the immediate release tablets.     

A pH-dependent colon-targeted oral drug delivery system using methacrylic acid copolymers. II. Manipulation of drug release using Eudragit L100 and Eudragit S100 combinations

Tablets containing mesalazine as a model drug were coated using various combinations of two methacrylic acid copolymers, (Eudragit® L100 and Eudragit S100) by spraying from aqueous systems. The Eudragit L100-Eudragit S100 (w/w) combinations studied were 1:0, 4:1, 3:2, 1:1, 2:3, 1:4, 1:5, and 0:1. The coated tablets were tested in vitro for their suitability for pH-dependent colon-targeted oral drug delivery. The dissolution profiles of the drug obtained from the studied tablets demonstrate that the release of the drug could be manipulated by changing the Eudragit L100-Eudragit S100 ratios in the combinations within the pH range between 6.0 and 7.0 in which the individual polymers are soluble, and a coating formulation consisting of a combination of the two polymers can overcome the issue of high gastrointestinal (GI) pH variability among individuals. The results also demonstrate the feasibility of using aqueous dispersions of Eudragit L100-Eudragit S100 combinations for coating tablets for colon-targeted delivery of drugs, and that the formulation can be adjusted to deliver drug(s) at any other desirable site of the intestinal region of the GI tract in which pH of the fluid is within the range 6.0 to 7.0. For colon-targeted delivery of drugs, the proposed combination system is superior to tablets coated with either Eudragit L100 or Eudragit S100 alone.     

Multiparticulate systems containing 5-aminosalicylic acid for the treatment of inflammatory bowel disease

Background: In recent years, many achievements have been realized in the therapy of inflammatory bowel disease (IBD) although its etiology remains unknown. Thus IBD treatment is symptomatic and targets general inflammatory mechanisms. Oral formulations containing 5-aminosalicylic acid (5-ASA) have become the standard therapy for mild-to-moderate IBD.

Objective: This article is a review of recently published research dealing with new 5-ASA dosage forms. Thus promising candidates for IBD treatment evaluated in vitro are reported; systems tested in vivo in trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats are mentioned; and 5-ASA formulations used in clinical studies are presented. Moreover, all oral dosage forms containing 5-ASA or its prodrugs are reviewed; their characteristics and utilization in IBD treatment are discussed.

Conclusion: In several clinical studies, it has been shown that multiparticulates such as pellets offer more advantages as compared with single unit forms, that is, coated tablets. Prolonged presence close to the site of the action, improved drug bioavailability, and easier administration of large drug doses belong to the benefits of pellets.     

Microspheres for the oral delivery of insulin: preparation,evaluation and hypoglycaemic effect in streptozotocin-induced diabetic rats

Insulin-loaded microspheres were prepared by alternating deposition film layers that were composed of insulin and poly(vinyl sulfate) potassium on the surface of poly(lactic acid) (PLA) microspheres. The preparation of the insulin-loaded microspheres was optimized by an orthogonal test design, and the relationship between drug loading (DL) and film layers was studied. The particle size, DL and encapsulation efficiency of the obtained insulin-loaded microspheres with 10 films were 5.25?±?0.15?µm, 111.33?±?1.15?mg/g and 33.7?±?0.19%, respectively. Following this, the physical characteristics of the insulin-loaded microspheres were investigated. The results from scanning electron microscopy and a laser particle size analyzer (LPSA) indicated the spherical morphology, rough surface and increasing particle sizes of the insulin-loaded microspheres, which were compared to those of PLA microspheres. An in vitro release study showed that the insulin-loaded microspheres were stable in HCl solution (pH 1.0) and released insulin slowly in phosphate-buffered solution (pH 6.8). Finally, the drug efficacy of the prepared insulin-loaded microspheres via oral administration was evaluated in rats with diabetes induced by streptozotocin, and an obvious dose-dependent hypoglycemic effect was observed. This preliminary data could illustrate the prospect of using microspheres for the oral delivery of insulin.     

Precursor system of liquid crystalline phase containing propolis microparticles for the treatment of periodontal disease: development and characterization

Precursor systems of liquid crystalline phase were prepared using the surfactant PPG-5-Ceteth-20, isopropyl myristate, and water; gelatin microparticles containing propolis were then added into these systems. Homogeneity of dispersion, the in-system microparticle morphology, and sedimentation behavior of each formulation were evaluated. The rheological and mechanical properties (hardness, compressibility, and adhesiveness), the work of syringing, and the propolis release profile were also evaluated. All the formulations exhibited pseudoplastic flow and thixotropy, and they displayed storage modulus, loss modulus, dynamic viscosity, and loss tangent that depended on temperature, frequency, and composition. Mechanical properties varied significantly among the formulations being affected by changes in the composition and temperature. Raising the concentration of surfactant and adding propolis microparticles significantly decreased the work of syringing. The drug release was non-Fickian (anomalous) and there was no significant difference between the tested systems in the times required for 10%, 30%, and 50% release of the initial drug loading.     

A novel application of iron oxide nanoparticles for detection of hydrogen peroxide in acid rain

Determining the concentration of hydrogen peroxide (H₂O₂) is of great importance in food, pharmaceutical, environmental and clinical analyses. Horseradish peroxidase (HRP), an enzyme specifically catalyzing the oxidative reaction of H₂O₂ to develop color reaction, has been widely used for measuring H₂O₂ concentration. However, owing to the instability and high cost of this enzyme, discovering efficient mimics of peroxidase has been important to conquer these disadvantages of protein catalyst. Recently we have found that Fe₃O₄ magnetic nanoparticles (Fe₃O₄ MNPs) possess intrinsic peroxidase-like activity, which can catalyze oxidation of various peroxidase substrates in the presence of H₂O₂. Based on this finding, we developed a spectrometric method using Fe₃O₄ MNPs as a catalyst to determine H₂O₂ in rainwater. Our data show that the Fe₃O₄ MNPs are efficient catalysts to determine H₂O₂ in rainwater. Compared to HRP, the Fe₃O₄ MNPs are reusable and economical and these characteristics make the particles a board range of applications in determining H₂O₂ in the rainwater.     

Is there the potential for an epidemic of variant Creutzfeldt–Jakob disease via blood transfusion in the UK?

The discovery of three individuals suspected to have contracted variant Creutzfeldt-Jakob disease (vCJD) through blood transfusions has heightened concerns that a secondary epidemic via human-to-human transmission could occur in the UK. The Department of Health responded immediately to this threat by banning those who had received blood transfusions since 1980 from donating blood. In this paper, we conduct a sensitivity analysis to explore the potential size of a blood-borne vCJD epidemic and investigate the effectiveness of public health interventions. A mathematical model was developed together with an expression for the basic reproduction number (R0). The sensitivity of model predictions to unknown parameters determining the transmission of vCJD via infected blood was assessed under pessimistic modelling assumptions. We found that the size of the epidemic (up until 2080) was bounded above by 900 cases, with self-sustaining epidemics (R0>1) also possible; but the scenarios under which such epidemics could arise were found to be biologically implausible. Under optimistic assumptions, public health interventions reduced the upper bound to 250 and further still when only biologically plausible scenarios were considered. Our results support the belief that scenarios leading to large or self-sustaining epidemics are possible but unlikely, and that public health interventions were effective.     

A promising codrug of nicotinic acid and ibuprofen for managing dyslipidemia. I: Synthesis and in vitro evaluation

Nicotinic acid is therapeutically the optimum antihyperlipidemic agent, yet its intolerable cutaneous flushing hinders its wide clinical implication. The codrug of nicotinic acid and ibuprofen (IBP) was synthesized in the aim of overcoming the troublesome side effect of nicotinic acid by blockade of prostaglandin synthesis through released IBP, thus enhance patient’s compliance. The physico-chemical properties of codrug namely solubility, partition coefficient, and pKa were determined. Its solubility in aqueous and organic solvents was highest in 0.1?M HCl and isopropanol, respectively. The kinetics of hydrolysis of the codrug and IBP 2-hydroxyethyl ester was studied in aqueous phosphate buffer solution in pH 1.2, 6.8, and 7.4 at 70°C, 80°C, and 90°C. The hydrolysis was found to be pH dependent and followed Arrhenius equation. The half-life of codrug and IBP 2-hydroxyethyl ester at 25°C in pH 7.4 was 218 days and 3 years, respectively. In vitro enzymatic hydrolysis of codrug and IBP 2-hydroxyethyl ester was studied in human plasma and rat liver homogenate. Codrug and IBP 2-hydroxyethyl ester exhibited faster in vitro enzymatic hydrolysis than in vitro chemical hydrolysis. The pseudo-first-order rate constants were 0.0113, 0.177?min^?1 for codrug and 0.0006, 0.0569?min^?1 for IBP 2-hydroxyethyl ester in human plasma and rat liver homogenate, respectively. Thus, nicotinic acid will be rapidly released from codrug to manage dyslipidemia, followed by the later release of IBP from IBP 2-hydroxyethyl ester to alleviate nicotinic acid cutaneous flushing.     

大菱鲆疾病早期快速检测方法——胶体金免疫层析试纸的研制与建立

使用成分单一的牛血清白蛋白(BSA)为模拟病原,以胶体金标记兔抗血清(即大菱鲆免疫球蛋白多抗)作为检测示踪物,并分别将BSA和葡萄球菌A蛋白印记到硝酸纤维素膜上制成检测线和对照线,通过一系列工艺创制与组装配套,首次成功制备了一套完整的大菱鲆抗体快速检测试纸。采用大菱鲆抗BSA血清作为阳性样本,以健康大菱鲆血清作为阴性样本,用以检验试纸的性能,并与酶联免疫吸附实验(ELISA)法检测结果相比较。结果表明:本试纸检测抗体的特异性与敏感性均很高,与ELISA方法相当,而且使用方便,不需专业技能和额外的试剂与辅助仪器设备,5 min内即可用裸眼获得观察结果,很适合于基层生产操作及户外调研使用。以该实验为基础建立起来的抗体检测试纸,亦可推广应用于其他病害抗体的检测,可为鱼类疾病早期发生提供简易、快捷和操作性强的诊断方法。