Conjugates of amphotericin B to resolve challenges associated with its delivery.

INTRODUCTION: Amphotericin B (AmB), a promising antifungal and antileishmanial drug, acts on the membrane of microorganisms. The clinical use of AmB is limited due to issues associated with its delivery including poor solubility and bioavailability, instability in acidic media, poor intestinal permeability, dose and aggregation state dependent toxicity, parenteral administration, and requirement of cold chain for transport and storage, etc. AREAS COVERED: Scientists have formulated and explored various covalent conjugates of AmB to reduce its toxicity with increase in solubility, oral bioavailability, and payload or loading of AmB by using various polymers, lipids, carbon-based nanocarriers, metallic nanoparticles, and vesicular carriers, etc. In this article, we have reviewed various conjugates of AmB with polymers and nanomaterials explored for its delivery to give a deep insight regarding further exploration in future. EXPERT OPINION: Covalent conjugates of AmB have been investigated by scientists, and preliminary in vitro and animal investigations have given successful results, which are required to be validated further with systematic investigation on safety and therapeutic efficacy in animals followed by clinical trials.

Application of a regional hurricane wind risk forecasting model for wood-frame houses.

Hurricane wind risk in a region changes over time due to changes in the number, type, locations, vulnerability, and value of buildings. A model was developed to quantitatively estimate changes over time in hurricane wind risk to wood-frame houses (defined in terms of potential for direct economic loss), and to estimate how different factors, such as building code changes and population growth, contribute to that change. The model, which is implemented in a simulation, produces a probability distribution of direct economic losses for each census tract in the study region at each time step in the specified time horizon. By changing parameter values and rerunning the analysis, the effects of different changes in the built environment on the hurricane risk trends can be estimated and the relative effectiveness of hypothetical mitigation strategies can be evaluated. Using a case study application for wood-frame houses in selected counties in North Carolina from 2000 to 2020, this article demonstrates how the hurricane wind risk forecasting model can be used: (1) to provide insight into the dynamics of regional hurricane wind risk-the total change in risk over time and the relative contribution of different factors to that change, and (2) to support mitigation planning. Insights from the case study include, for example, that the many factors contributing to hurricane wind risk for wood-frame houses interact in a way that is difficult to predict a priori, and that in the case study, the reduction in hurricane losses due to vulnerability changes (e.g., building code changes) is approximately equal to the increase in losses due to building inventory growth. The potential for the model to support risk communication is also discussed.