A Novel Tropically Stable Oral Amphotericin B Formulation (iCo-010) Exhibits Efficacy against Visceral Leishmaniasis in a Murine Model

Visceral leishmaniasis (VL) is a systemic form of a vector-borne parasitic disease caused by obligate intra-macrophage protozoa of the genus Leishmania. VL is always fatal in humans if left untreated and treatment options are limited. Amphotericin B (AmB), a polyene antibiotic, is the most active antileishmanial agent that currently exists. Liposomal AmB (AmBisome) is used as first-line treatment in developed countries [1], [7], [8], [9], [10]; however, the requisite parenteral administration and the high cost of the liposomal formulation prevents this treatment from reaching the majority of patients in developing nations [3]. A stable, efficacious oral treatment for VL that is able to withstand the rigors of tropical climates would overcome many of the current barriers to treatment that exist in countries with large VL-infected patient populations. In this study we have developed an oral formulation of AmB that is stable in tropical conditions and exhibits significant antileshimanial activity in mice

Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines

There has been an escalating interest in the medicinal use of Cannabis sativa in recent years. Cannabis is often administered orally with fat-containing foods, or in lipid-based pharmaceutical preparations. However, the impact of lipids on the exposure of patients to cannabis components has not been explored. Therefore, the aim of this study is to elucidate the effect of oral co-administration of lipids on the exposure to two main active cannabinoids, ?9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In this study, oral co-administration of lipids enhanced the systemic exposure of rats to THC and CBD by 2.5-fold and 3-fold, respectively, compared to lipid-free formulations. In vitro lipolysis was conducted to explore the effect of lipids on the intestinal solubilisation of cannabinoids. More than 30% of THC and CBD were distributed into micellar fraction following lipolysis, suggesting that at least one-third of the administered dose will be available for absorption following co-administration with lipids. Both cannabinoids showed very high affinity for artificial CM-like particles, as well as for rat and human CM, suggesting high potential for intestinal lymphatic transport. Moreover, comparable affinity of cannabinoids for rat and human CM suggests that similar increased exposure effects may be expected in humans. In conclusion, co-administration of dietary lipids or pharmaceutical lipid excipients has the potential to substantially increase the exposure to orally administered cannabis and cannabis-based medicines. The increase in patient exposure to cannabinoids is of high clinical importance as it could affect the therapeutic effect, but also toxicity, of orally administered cannabis or cannabis-based medicines

Which New Approaches to Tackling Neglected Tropical Diseases Show Promise?

This PLoS Medicine Debate examines the different approaches that can be taken to tackle neglected tropical diseases (NTDs). Some commentators, like Jerry Spiegel and colleagues from the University of British Columbia, feel there has been too much focus on the biomedical mechanisms and drug development for NTDs, at the expense of attention to the social determinants of disease. Burton Singer argues that this represents another example of the inappropriate “overmedicalization” of contemporary tropical disease control. Peter Hotez and colleagues, in contrast, argue that the best return on investment will continue to be mass drug administration for NTDs

Discovery and Development of Toll-Like Receptor 4 (TLR4) Antagonists: A New Paradigm for Treating Sepsis and Other Diseases

Abstract. Sepsis remains the most common cause of death in intensive care units in the USA, with a current estimate of at least 750,000 cases per year, and 215,000 deaths annually. Despite extensive research still we do not quite understand the cellular and molecular mechanisms that are involved in triggering and propagation of septic injury. Endotoxin (lipopolysaccharide from Gram-negative bacteria, or LPS) has been implicated as a major cause of this syndrome. Inflammatory shock as a consequence of LPS release remains a serious clinical concern. In humans, inflammatory responses to LPS result in the release of cytokines and other cell mediators from monocytes and macrophages, which can cause fever, shock, organ failure and death. A number of different approaches have been investigated to try to treat and/or prevent the septic shock associated with infections caused by Gram-negative bacteria, including blockage of one or more of the cytokines induced by LPS. Recently several novel amphipathic compounds have been developed as direct LPS antagonists at the LPS receptor, TLR4. This review article will outline the current knowledge on the TLR4-LPS synthesis and discuss the signaling, in vitro pre-clinical and in vivo clinical evaluation of TLR4 antagonists and their potential use in sepsis and a variety of diseases such as atherosclerosis as well as hepatic and renal malfunction. KEY WORDS: drug discovery; LPS; sepsis; toll-like receptor antagonists

Effects of climate change on soil health resulting in an increased global spread of neglected tropical diseases.

Although it is commonly accepted that climate change will increase the range and abundance of neglected tropical diseases (NTDs) through increased rainfall and temperature, the role of soil and influence of soil health on this effect is not well understood. We propose that understanding the influence of climate change on the physical, chemical, and biological characteristics of soils can explain how favourable environmental conditions for NTDs and vectors of NTDs to reproduce form. This, in turn, can assist local public health experts in predicting and managing the spread of NTDs. We also suggest that unlike unpredictable climatic factors, soil health can be directly managed through appropriate land use practices. This viewpoint seeks to start a discussion between soil scientists and healthcare professionals on how to achieve common goals and strategies required to manage the spread of NTDs

Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape—A Summary of This Indispensable Special Issue

Canadian Pharmaceutical Scientists have a rich history of groundbreaking research in pharmacokinetics and drug metabolism undertaken primarily throughout its Pharmacy Faculties and within the Pharmaceutical and Biotechnology industry.[...

Role of lipid and lipoprotein metabolizing enzymes in the development of atherosclerosis

14-25Cardiovascular disease is the primary cause of mortality in developed and  developing  nations. With an increase in the aging population, there is a surge in the incidence of atheroscleortic  cardiovascular diseases. One of the most common and lethal manifestations of athe rosclerosis is coronary heart disease, accounting for 50% of the atherosclerotic cardiovascular diseases in men and women younger than 75 years. Peripheral arterial diseases, manifested mainly as intermittent  claudication  constitute approximately 10% of the atherosclerotic cardiovascular events . According to the American Heart Association 2001 Heart and Stroke Statistical Update, atherosclerosis accounts for 75% of all deaths due to cardiovascular diseases. Therfore, atherosclerosis continues to remain the primary cause of health concern for the population at large. The aim of this review is to discuss the role of enzymes that are involved in the metabolism of lipid and lipoproteins in the development of atherosclerosis

Neglected Populations: Safeguarding the Health of Street-Involved Children in Ghana.

Ensuring the health of street-involved children is a growing public health challenge. These children are vulnerable, neglected, and rarely a priority for basic service providers and governments. Sizable populations of street-involved children are present in major urban areas worldwide and current trends in urbanization suggest these populations will grow in the coming years. Whilst migration offers employment and training opportunities, the health and wellbeing of children is negatively impacted by their interactions with the streets. However, systemic barriers may also prevent these children from achieving an adequate health status. The situation of street-involved children in Ghana, West Africa will be discussed. PUBLISHING NOTE: This is the pre-peer reviewed version of the following article: Neglected Populations: Safeguarding the Health of Street-Involved Children in Ghana, JA Osei-Twum and KM Wasan, Journal of Pharmaceutical Sciences, 101/10, 2012, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/jps.23255/abstract;jsessionid=91506BF55A0444C249D7D0D7276270FD.d03t03.Pharmaceutical Sciences, Faculty ofUnreviewedGraduat

Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape

Canadian Pharmaceutical Scientists have a rich history of ground-breaking research in pharmacokinetics and drug metabolism undertaken throughout its Pharmacy and Medical Schools and within the Pharmaceutical and biotechnology industry. The principle of drug Absorption, Distribution, Metabolism and Excretion (ADME) is the foundational basis of rationale drug-design, and pharmacotherapy. The study of ADME and its descriptive quantitative analysis is the basis of pharmacokinetics. Pharmacokinetics is fundamental in the development of a new chemical entity into a marketable product and is essential in understanding the bioavailability, bioequivalence and biosimilarities of drugs. Pharmacokinetics and drug development studies facilitate an understanding of organ-based functionality. Population pharmacokinetic variability and the modeling of drug concentrations has significant utility in translating individual response in a target patient population. This special issue serves to highlight and capture the contemporary progress and current landscape of pharmacokinetics and drug metabolism within the prevailing Canadian context. We invite articles on all aspects of Pharmacokinetics and Drug Metabolism studies highlighting the world-class research currently undertaken in Canada for this special issue