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Advances in Drug Development
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Journal of Bioanalysis & Biomedicine

ISSN: 1948-593X

Open Access

Advances in Drug Development

Special Issue Article

Pages: 1 - 6

Defensins: More than Nature’s Anti-bug Spray?

Erik de Leeuw

DOI:

DOI: 10.4172/1948-593X.S8-001

Human defensins were originally identified as natural antimicrobial peptides that protect the host from infections. More recently, novel biological functions of these peptides have been described, expanding their role as natural antimicrobials. Here, our current understanding of this expanding role of human α-defensins is reviewed, with emphasis on antibacterial killing, bacterial toxin neutralization and immunity.

Editorial

Pages: 1 - 1

A Perspective on Antivirals

Erik de Leeuw

DOI:

DOI: 10.4172/1948-593X.S8-e001

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Review Article

Pages: 1 - 14

Phage Therapy: Emergent Property Pharmacology

Andrew J. Curtright and Stephen T. Abedon

DOI:

DOI: 10.4172/1948-593X.S6-002

Phage therapy is the application to bodies of bacteriophages – the viruses of bacteria. This is done to combat bacterial infections. In this article we combine three themes, phage therapy, pharmacology, and the concept of emergent properties. We do this to explore what is unique along with what is not so unique about phage therapy, as viewed from a pharmacological standpoint. At the same time, we consider the place of phage therapy, and drugs generally, within the larger scheme that is biology. We make these latter considerations predominantly in terms of emergent properties, which are system characteristics that exist, qualitatively, at ‘higher’ but not ‘lower’ levels of organization. The latter is a relevant consideration especially in exploring the pharmacology of ‘living’ antibacterials, as are phages, which at lower levels can be viewed as collections of numerous molecules and biochemical pathways but which at higher levels become organized into somewhat complex entities that are capable of ‘self amplification’. Emergent properties are also prominently relevant to pharmacology, more generally, as they give rise to requirements for animal along with clinical testing to identify otherwise unexpected drug characteristics. Our broader goal is to stimulate a better integration of issues of phage therapy and pharmacology, predominantly in light of the substantial complexity of phages in comparison with chemical drugs and towards furthering the rational development of phagebased antibacterial strategies. Our chief conclusion is that while phages, due to their complexity, potentially possess numerous emergent properties when compared with less-complex antibacterials, in fact other aspects of phages – including their relative benignness, environmental ubiquity, and that their antibacterial properties are products of evolution – can allow for certain simplifications to pharmacological development. These simplifications are not as readily achieved by chemical drugs, such as antibiotics, which can possess negative properties that are difficult to predict.

Research Article

Pages: 1 - 18

Purity profiling of Peptide Drugs

Sylvia Van Dorpe, Mathieu Verbeken, Evelien Wynendaele and Bart De Spiegeleer

DOI:

DOI: 10.4172/1948-593X.S6-003

The quality of a peptide drug mainly depends on its impurity profile, with the emphasis on the related impurities. These impurities may be biomedically active, alter the desired efficacy or induce unwanted toxicity, an aspect which is termed the “functional quality” of the peptide drug. Therefore, regulatory authorities have set up guidances or have legally established specification limits to assure a consistent purity of these peptide drugs. For the active pharmaceutical ingredients (APIs), the pharmacopoeial monographs are legally binding. Additional information can be found in regional and international guidelines. For the finished pharmaceutical drug products (FDPs) containing peptide active ingredients, only general guidelines are available. The construction of a complete related-impurity profile is very challenging due to the wide availability of different protecting groups, coupling agents and additives that may be used during peptide synthesis. In addition, chemical degradation, occurring during synthesis, formulation or at storage, may occur as well, including not only so-called pure chemical degradation but interaction with excipients as well. This review provides an update of the regulatory and scientific rationales behind the related impurities in peptide drugs.

 

Review Article

Pages: 1 - 3

The Anticancer Activity of Hypericin in Photodynamic Therapy

K Maduray and LM Davids

DOI:

DOI: 10.4172/1948-593X.S6-004

Photodynamic therapy (PDT) is a cancer treatment that requires the interaction of a photosensitizer (PS), light and oxygen. A PS is characterised as a non-toxic drug or dye which is excited using light from a laser source at a specific wavelength. The excited PS will react with oxygen present in biological tissue to produce reactive oxygen species (ROS) that destroys cancerous cells by inducing cell death. The PS uptake by cancerous tissue in combination with localised light delivery makes PDT an effective oncology treatment that prevents damage to surrounding normal healthy tissue. To date, most photosensitizers (PSs) for PDT have been chemically synthesized and modified to satisfy the demands for an ideal PS. However, a naturally occurring red plant pigment (Hypericin) has drawn increased interest recently as a new generation PDT drug. It is known to have high quantum yields, tumor selectivity and low production costs. Other beneficial properties of hypericin include low photobleaching, low cytotoxicity in the absence of light and no mutagenicity. Several in vitro and in vivo studies have established its anticancer potential upon irradiation with laser light.

Review Article

Pages: 1 - 6

Principles and Scientific Basis of Traditional Chinese Medicine in Cancer Treatment

Bing Hu, Qin Du, Ke-Ping Shen and Ling Xu

DOI:

DOI: 10.4172/1948-593X.S6-005

Traditional Chinese Medicine (TCM) have been used to reduce toxic effects and enhance therapeutic effects of modern cancer therapy, palliate clinical syndrome or improve quality of life, enhance immune function, prevent recurrence and metastasis, and anti-cancer therapy for patients failed in or refuse to conventional treatment. From TCM perspective, the pathogenesis of cancer is related to weakened body resistance, blood stasis, phlegm stagnation and toxicity accumulation, and cancer are recognized as syndrome of blood-stasis, phlegm and toxicity in TCM. Syndrome Differential Treatment is the basic principle for cancer treatment. Anti-cancer effects of Chinese herb are associated with apoptosis, cell senescence, autophagy and other mechanisms. Chinese herbal formula is the major application form of Chinese herb. Most TCM physicians prescribe or combine multiple herbs for a formula or prescription based on TCM principles, pharmacological progression and personal experience. We emphasize application of anti-cancer herb must guided by TCM principles. There is a great need to explore the combination rule of anti-cancer herbs, and establish effective herbal formulas for various situations in cancer treatment.

Research Article

Pages: 1 - 7

Bioanalytical Method Development, Validation and Quantification of Metaxalone in Rat Plasma by Liquid Chromatography Tandem Mass Spectrometry

Karthikeyan Kandasamy, Vasantharaju Surenahalli Gowdra, Hariprabhu Nammalvar and ArulKumaran Kottur S Govindarajan

DOI:

DOI: 10.4172/1948-593X.S6-006

A simple, highly sensitive, precise and accurate high-performance liquid chromatographic (LCMSMS) method with mass detection was developed and validated for the rapid quantification of metaxalone (CAS Registry No, 1665- 48-1) in rat plasma samples. The chromatographic separation was achieved with a reverse phase column Agilent XDB C18 (4.6×100 mm, 5μ) and the mobile phase consisted of methanol and 5 mm ammonium acetate buffer (80:20 v/v) as eluent, at a flow rate of 0.6 mL/min. Phenytoin (CAS Registry no, 57-41-0) was used as an internal standard. The effluence was ionized by positive electrospray ionization and measured by mass spectrometry. The retention time of metaxalone and phenytoin were found to be 1.60 and 1.83 min respectively. The calibration curve was linear (r2 > or = 0.99) ranging from 0.98 to 998 ng/ml and the lower limit of quantification was 0.98 ng/mL. Interday and Intraday precision were lower than 5% (CV) and accuracy ranged from 90 to 110% in terms of percent accuracy. Mean extraction recovery was found to be above 82%. The method was successfully demonstrated for evaluation of pharmacokinetic profile of metaxalone in male Sprague dawley rats and validated for excellent selectivity, accuracy, precision, recovery and stability.

Research Article

Pages: 1 - 5

Validation of a Simple, Rapid and Sensitive LC Method for Quantification of Riluzole in Rat Plasma and its Pharmacokinetic Application

Punna Rao Ravi, Rahul Vats and Kora Upendra Reddy

DOI:

DOI: 10.4172/1948-593X.S6-007

A simple, sensitive and rapid high-performance liquid chromatography method with ultraviolet (UV) detector was developed and validated for the analysis of riluzole (RLZ) in rat plasma. The plasma sample, spiked with nebivolol as an internal standard (IS), was subjected to a single step protein precipitation prior to analysis. Chromatographic separation was achieved on a Phenomenex C18 (250 mm× 4.6 mm, 5 μm) column. A combination of methanol and phosphate buffer (25 mM KH2PO4, pH 3.5), in the ratio of 70:30% v/v was used as the mobile phase in isocratic mode. RLZ and IS were monitored at wavelengths of 264 nm and 280 nm respectively. No interference was observed from plasma components in the analysis of RLZ and IS. The calibration curve was linear over the range of 50–4000 ng/mL (r2 = 0.999). The drug was found to be stable under various processing and storage conditions. The assay provided good reproducibility, accuracy and proved to be suitable for oral pharmacokinetic studies of RLZ in rats.

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