Parenteral amphotericin B has been considered as first-line therapy in the treatment of systemic fungal and parasitic infections, however its use has been associated with a number of limitations including affordability, accessibility, and an array of systemic toxicities. Until very recently, it has been very challenging to develop a bioavailable formulation of amphotericin B due to its physical chemical properties, limited water and lipid solubility, and poor absorption. This perspective reviews several novel oral Amphotericin B formulations under development that are attempting to overcome these limitations.

The unique properties of chitosan make it a useful choice for various nanoparticulate drug delivery applications. Although chitosan is biocompatible and enables cellular uptake, its interactions at cellular and systemic levels need to be studied in more depth. This review focuses on the various physical and chemical properties of chitosan that affect its performance in biological systems. We aim to analyze recent research studying interactions of chitosan nanoparticles (NPs) upon their cellular uptake and their journey through the various compartments of the cell. The positive charge of chitosan enables it to efficiently attach to cells, increasing the probability of cellular uptake. Chitosan NPs are taken up by cells via different pathways and escape endosomal degradation due to the proton sponge effect. Furthermore, we have reviewed the interaction of chitosan NPs upon in vivo administration. Chitosan NPs are immediately surrounded by a serum protein corona in systemic circulation upon intravenous administration, and their biodistribution is mainly to the liver and spleen indicating RES uptake. However, the evasion of RES system as well as the targeting ability and bioavailability of chitosan NPs can be improved by utilizing specific routes of administration and covalent modifications of surface properties. Ongoing clinical trials of chitosan formulations for therapeutic applications are paving the way for the introduction of chitosan into the pharmaceutical market and for their toxicological evaluation. Chitosan provides specific biophysical properties for effective and tunable cellular uptake and systemic delivery for a wide range of applications.

In a previous analysis, six major threats to at-risk species in Canada were quantified: habitat loss, introduced species, over-exploitation, pollution, native species interactions and natural causes (Venter et al. 2006). Because of rapid environmental change in Canada, and an enhanced understanding of the drivers of species endangerment, we updated the 2005 analysis, and tested for changes in threats up until the end of 2018. We also expanded the scope to acknowledge climate change as a seventh major threat to species, given its increasing importance for reshaping biological communities. Using information on the COSEWIC (Committee on the Status of Endangered Wildlife in Canada) website (http://www.cosewic.ca/index.php/en-ca/), we scored the threats for each of 814 species. Habitat loss remained the most important anthropogenic threat to Canada’s at-risk species, affecting 82% of species, followed by over-exploitation (47%), introduced species (46%) and pollution (35%). Climate change was the least important threat, affecting only 13% of species. However, report writers used less certain language when talking about climate change compared to other threats, so when we included cases where climate change was listed as a probable or future cause, climate change was the fourth most important anthropogenic threat, affecting some 38% of species. The prevalence of threat categories was broadly similar to those for the United States and IUCN listed species. The taxa most affected by climate change included lichens (77%), birds (63%), marine mammals (60%) and Arctic species of all taxa (79%), whereas vascular plants (23%), marine fishes (24%), arthropods (27%), and non-Arctic species (35%) were least affected. A paired analysis of the 188 species with two or more reports indicated that any mention of climate change as a threat increased from 12 to 50% in 10 years. Other anthropogenic threats that have increased significantly over time in the paired analysis included introduced species, over-exploitation, and pollution. Our analysis suggests that threats are changing rapidly over time, emphasizing the need to monitor future trends of all threats, including climate change.

There have been several studies that have linked elevated scavenger receptor class b type 1 (SR-B1) expression and activity to the development and progression of castration-resistant prostate cancer (CRPC). SR-B1 facilitates the influx of cholesterol to the cell from lipoproteins in systemic circulation. This influx of cholesterol may be important for many cellular functions, including the synthesis of androgens. Castration-resistant prostate cancer tumors can synthesize androgens de novo to supplement the loss of exogenous sources often induced by androgen deprivation therapy. Silencing of SR-B1 may impact the ability of prostate cancer cells, particularly those of the castration-resistant state, to maintain the intracellular supply of androgens by removing a supply of cholesterol. SR-B1 expression is elevated in CRPC models and has been linked to poor survival of patients. The overarching belief has been that cholesterol modulation, through either synthesis or uptake inhibition, will impact essential signaling processes, impeding the proliferation of prostate cancer. The reduction in cellular cholesterol availability can impede prostate cancer proliferation through both decreased steroid synthesis and steroid-independent mechanisms, providing a potential therapeutic target for the treatment of prostate cancer. In this article, we discuss and highlight the work on SR-B1 as a potential novel drug target for CRPC management.