Interaction between antioxidants in assays of total antioxidant capacity

Sub-additivity of antioxidant activities in assays of total antioxidant capacity has been reported previously and ascribed to binding of low-molecular weight antioxidants such as flavonoids by proteins. We demonstrate that this phenomenon is much more common and concerns also interactions between typical low-molecular weight oxidants in the assays of ABTS- decolorization and protection of fluorescein from AAPH-induced bleaching. The subadditive interactions between antioxidants may affect quantitative considerations drawn from in vitro assays of antioxidant capacity of biological samples.     

Self-emulsifying drug delivery system and the applications in herbal drugs

Abstract

Herbal drugs have been used for thousands of years in the east and have had a recent resurgence in popularity among consumers in the west. However, most of herbal drug are poorly soluble and have hydrophobic properties and poor distribution, leading to reduced bioavailability and hence decreased treatment efficacy, requiring repeated administration or increased dose. In the past few decades, considerable attention has been focused on the development of self-emulsifying drug delivery system (SEDDS) for herbal drugs. SEDDS is isotropic and thermodynamically stable solutions consisting of oil, surfactant, co-surfactant and drug that can spontaneously form oil-in-water micro/nanoemulsion when mixed with water under gentle stirring. The formulation can be a viable alternative to classical formulations to take advantage of their lipophilic nature and to solve their problems of poor solubility, poor bioavailability, low oral absorption and instability. The mechanism of self-emulsification, solubility studies, construction of phase diagram, optimization and characterization of herbal drugs-loaded SEDDS formulation and in situ absorption evaluation of herbal drugs in rat intestine are presented in our article.     

固相微提取及其在滥用药物分析中的应用

生物样品中的药物及其代谢物的分析常可分为样品制备和定量测定等方面,其中样品制备包括分析物的提取、纯化和浓缩等步骤.     

Fluorescence lifetime assays: current advances and applications in drug discovery

Introduction: Fluorescence lifetime assays complement the portfolio of established assay formats available in drug discovery, particularly with the recent advances in microplate readers and the commercial availability of novel fluorescent labels. Fluorescence lifetime assists in lowering complexity of compound screening assays, affording a modular, toolbox-like approach to assay development and yielding robust homogeneous assays. Areas covered: To date, materials and procedures have been reported for biochemical assays on proteases, as well as on protein kinases and phosphatases. This article gives an overview of two assay families, distinguished by the origin of the fluorescence signal modulation. Expert opinion: The pharmaceutical industry demands techniques with a robust, integrated compound profiling process and short turnaround times. Fluorescence lifetime assays have already helped the drug discovery field, in this sense, by enhancing productivity during the hit-to-lead and lead optimization phases. Future work will focus on covering other biochemical molecular modifications by investigating the detailed photo-physical mechanisms underlying the fluorescence signal.     

Fluorescence lifetime assays: current advances and applications in drug discovery

Introduction: Fluorescence lifetime assays complement the portfolio of established assay formats available in drug discovery, particularly with the recent advances in microplate readers and the commercial availability of novel fluorescent labels. Fluorescence lifetime assists in lowering complexity of compound screening assays, affording a modular, toolbox-like approach to assay development and yielding robust homogeneous assays.

Areas covered: To date, materials and procedures have been reported for biochemical assays on proteases, as well as on protein kinases and phosphatases. This article gives an overview of two assay families, distinguished by the origin of the fluorescence signal modulation.

Expert opinion: The pharmaceutical industry demands techniques with a robust, integrated compound profiling process and short turnaround times. Fluorescence lifetime assays have already helped the drug discovery field, in this sense, by enhancing productivity during the hit-to-lead and lead optimization phases. Future work will focus on covering other biochemical molecular modifications by investigating the detailed photo-physical mechanisms underlying the fluorescence signal.     

DART-质谱及其在药物分析中的应用

介绍一种非表面接触型大气压解析/离子化质谱新技术—实时直接分析(DART)及其在药物定性、定量分析中的应用。在环境空气条件下,样品表面的化合物经中性或惰性气体(如氮气、氦气或氩气)放电产生的激发态原子瞬间脱附并离子化,以质谱或串联质谱检测。该技术无需样品预处理,或仅需要简单的样品前处理,具有抗基质干扰、无溶剂效应、分析周期短(2～3 s)、直接、原位、无损、快速和现场等特点。文中重点介绍了DART在药品鉴别、药物合成反应监测、药代动力学研究和滥用药物监测等方面的应用,并对该技术在药物分析领域中的应用前景进行了展望。     

Potential applications of ferrocene as a structural feature in antioxidants

Comparing with the wide usage of ferrocene in novel materials, ferrocene was unusually applied to be a structural feature in designing drugs even though some researchers pointed out that ferrocene and its derivatives possessed potential pharmacological applications. This was due to that low polarity limited bioavailability of ferrocene in vivo. Since ferrocene was inert to the oxidation at atmosphere, it was deduced that synthetic derivatives of ferrocene may be a novel kind of antioxidant, in which other organic groups may enhance the bioavailability of ferrocene, or large conjugated system formed among ferrocenyl and other organic groups may increase the antioxidant effectiveness. Thus, synthetic derivatives of ferrocene were divided into nonconjugated and conjugated ones in this review. For nonconjugated ferrocenyl derivatives, carbon chain or simple group attached one or two cyclopentadienyl rings in ferrocene to form a novel molecule with ferrocenyl group. The aim of synthesis of nonconjugated ferrocenyl compounds was to increase the bioavailability of ferrocene in vivo. On the other hand, the conjugated ferrocenyl derivatives referred to introduce other group to form a conjugated system with the cyclopentadienyl ring in ferrocene. The large conjugated system was beneficial for the single electron to dispense among the whole molecule while forming radicals, and enhanced the antioxidant capacity of the whole molecule. This review summarized the potential usage of ferrocene in antioxidants.     

A comparative study of stabilising effect and antioxidant activity of different antioxidants on levodopa-loaded liposomes

The aim of this study was to evaluate the stability of levodopa liposomes co-loaded with three different antioxidants (curcumin, ascorbic acid, and superoxide dismutase (SOD)). For this purpose, multilamellar liposomes were prepared. Curcumin was added into the lipid bilayer while ascorbic acid and SOD were placed into the aqueous phase. The influence of preparation technique and surface charge were also investigated. Vesicles were characterised and free radical scavenging potential was determined. From stability study, ascorbic acid showed better stabilising effect. These co-loaded liposomes also exhibited potential radical scavenging activity where ascorbic acid played a key role. From the study of different preparation techniques and charge, we concluded that cationic liposomes made by Thin Layer Evaporation following extrusion offered the best physicochemical and stability properties. A dual mechanism of these liposomes implies the chemical stabilisation of levodopa (dose reduction) and the antioxidant effect, with a preventive effect on Parkinson’s disease.     

pH and its applications in targeted drug delivery

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Polypharmacy (herbal and synthetic drug combination): a novel approach in the treatment of type-2 diabetes and its complications in rats

The aim of present study was to evaluate the effect of aqueous leaf extract of Annona squamosa with Glipizide in a high fat diet and streptozocin-induced type-2 diabetes. Nine groups (n = 6) of male Sprague-Dawley rats were used for the study, with. Basal blood glucose, urine volume, and body weights were measured and the rate were kept on a high fat diet. After 15 days, streptozocin in sub-diabetic dose (35 mg/kg) was administered to the animals to induce diabetes. With 1 week of consistent hyperglycemia, treatment was initiated. Aqueous extract of Annona squamosa was administered orally at 350 mg/kg body weight alone and in combination with reduced and reducing dose combinations of Glipizide. Blood glucose, body weight, urine volume were measured every 10th day. The elevated blood-glucose level in diabetic rats was controlled better with combination therapy compared with the synthetic drug alone or the herbal stand-alone drug. All the results were statistically significant (P < 0.001). A combination of Annona squamosa along with Glipizide may be helpful in dose reduction of Glipizide up to 50 %, reducing the risk of the onset of insulin therapy.     

肝脏灌流技术及其在药物研究中的应用进展

肝脏灌流技术在药物研究的应用已有几十年历史。与其他体外方法相比 ,肝脏灌流具有显著的优点 ,是研究药物代谢与生物转化、药物相互作用、药物对肝脏作用的理想模型 ,至今仍在药物研究中发挥重要作用。该文对该技术及其在药物研究中的应用进展进行了综述     

Orlistat: its current status as an anti-obesity drug

Orlistat is a non-centrally acting anti-obesity agent that acts locally in the gastrointestinal tract to inhibit lipase, an enzyme that is crucial for the digestion of long-chain triglycerides. At the recommended dose of 120 mg three times daily, orlistat inhibits dietary fat absorption by about 30%. Over a 1-year period, obese patients taking orlistat in combination with a hypocaloric diet show a reduction of 2–5 kg over the weight decrease with placebo. When continued for a second year in combination with a weight maintenance diet, orlistat reduces weight regain compared to placebo-treated patients. Orlistat in combination with dietary intervention is also associated with beneficial effects on cardiovascular risk factors including total and low-density lipoprotein cholesterol, blood pressure and plasma glucose. It is not known if orlistat has any impact on clinical outcomes such as myocardial infarction, stroke and sudden death. Orlistat has not been compared with other anti-obesity agents.     

Green fluorescent protein (GFP): applications in cell-based assays for drug discovery

Green fluorescent protein (GFP) is a powerful tool for cell-based assays owing to the intrinsic fluorescence of this protein that allows real-time analysis of molecular events in living cells. A number of GFP variants have been developed with optimal properties for both high-throughput screening and high-content screening. The author discusses advances in basic GFP technology, including the discovery of fluorescent proteins from divergent bioluminescent species, as well as the development of various GFP biosensors suited to the drug discovery process.     

Dendrimers as versatile platform in drug delivery applications

About forty percent of newly developed drugs are rejected by the pharmaceutical industry and will never benefit a patient because of poor bioavailability due to low water solubility and/or cell membrane permeability. New delivery technologies could help to overcome this challenge. Nanostructures with uniform and well-defined particle size and shape are of eminent interest in biomedical applications because of their ability to cross cell membranes and to reduce the risk of premature clearance from the body. The high level of control over the dendritic architecture (size, branching density, surface functionality) makes dendrimers ideal carriers in these applications. Many commercial small molecule drugs with anticancer, anti-inflammatory, and antimicrobial activity have been successfully associated with dendrimers such as poly(amidoamine) (PAMAM), poly(propylene imine) (PPI or DAB) and poly(etherhydroxylamine) (PEHAM) dendrimers, either via physical interactions or through chemical bonding (‘prodrug approach’). Targeted delivery is possible via targeting ligands conjugated to the dendrimer surface or via the enhanced permeability and retention (EPR) effect. The biocompatibility of dendrimers follows patterns known from other small particles. Cationic surfaces show cytotoxicity; however, derivatization with fatty acid or PEG chains, reducing the overall charge density and minimizing contact between cell surfaces and dendrimers, can reduce toxic effects.     

Quercetin-phospholipid complex: an amorphous pharmaceutical system in herbal drug delivery

Development of amphiphilic drug-lipid complexes is a potential approach for improving therapeutic efficacy of the drugs by increasing solubility, release profile and oral bioavailability. Quercetin (3, 3', 4', 5, 7-pentahydroxyflavone), a polyphenolic flavonoid, shows several biological effects like anti-inflammatory, anti-cancer, antiproliferative, antimutagenic and apoptosis induction but its use is limited due to its low aqueous solubility. To overcome this limitation, a value added phospholipid complex of quercetin was developed to improve its aqueous solubility for better absorption through the gastrointestinal tract and this might result in improved bioavailability. The quercetin-phospholipid complex thus prepared was evaluated for various physico-chemical parameters like infra red spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), scanning electron microscopy (SEM) and solubility study. The In vitro antioxidant activity was also studied. The phospholipid complex of quercetin was found to be fluffy and porous with rough surface in SEM. FTIR, DSC and XRPD data confirmed the formation of phospholipid complex. The water solubility of quercetin was improved by 12 folds (from 3.44 μg/ ml to 36.81 μg/ ml) in the prepared complex. There was no statistical difference between the quercetin complex and quercetin in the In vitro anti-oxidant activity, indicating that the process of complexation did not adversely affect the bioactivity of the active ingredient.     

The androgen receptor and its use in biological assays: looking toward effect-based testing and its applications

Steroid abuse is a growing problem among amateur and professional athletes. Because of an inundation of newly and illegally synthesized steroids with minor structural modifications and other designer steroid receptor modulators, there is a need to develop new methods of detection which do not require prior knowledge of the abused steroid structure. The number of designer steroids currently being abused is unknown because detection methods in general are only identifying substances with a known structure. The detection of doping is moving away from merely checking for exposure to prohibited substance toward detecting an effect of prohibited substances, as biological assays can do. Cell-based biological assays are the next generation of assays which should be utilized by antidoping laboratories; they can detect androgenic anabolic steroid and other human androgen receptor (hAR) ligand presence without knowledge of their structure and assess the relative biological activity of these compounds. This review summarizes the hAR and its action and discusses its relevance to sports doping and its use in biological assays.     

High-content analysis for drug delivery and nanoparticle applications

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The antioxidant response as a drug target in diabetic neuropathy

While increasing antioxidant potential is an attractive treatment strategy for diabetic neuropathy, many years of trials using high-dose oral antioxidants have not produced therapeutic results. An increasing understanding of the innate antioxidant response and the pharmacological agents that can regulate this mechanism may open new avenue for drug development. This review describes the current state of antioxidant trials and the potential for targeting the antioxidant response. In combination with antihyperglycemic agents, agents that regulate the antioxidant response may afford superior protection against cellular oxidative injury in diabetes.