Sol-moiety: Discovery of a water-soluble prodrug technology for enhanced oral bioavailability of insoluble therapeutics.

Though conceptually attractive, the use of water-soluble prodrug technology to enhance oral bioavailability of highly insoluble small molecule therapeutics has not been widely adopted. In large part, this is due to the rapid enzymatic or chemical hydrolysis of prodrugs within the gastrointestinal tract, resulting in drug precipitation and no overall improvement in oral bioavailability relative to standard formulation strategies. We reasoned that an optimal water-soluble prodrug could be attained if the rate of prodrug hydrolysis were reduced to favor drug absorption rather than drug precipitation. In doing so, the rate of hydrolysis provides a pharmacokinetic control point for drug delivery. Herein, we report the discovery of a water-soluble promoiety (Sol-moiety) technology to optimize the oral bioavailability of highly insoluble small molecule therapeutics, possessing various functional groups, without the need for sophisticated, often toxic, lipid or organic solvent-based formulations. The power of the technology is demonstrated with marked pharmacokinetic improvement of the commercial drugs enzalutamide, vemurafenib, and paclitaxel. This led to a successful efficacy study of a water-soluble orally administered prodrug of paclitaxel in a mouse pancreatic tumor model.

An Evolving HIV Epidemic in the Middle East and North Africa (MENA) Region: A Scoping Review.

Human immunodeficiency virus (HIV) in the Middle East and North Africa (MENA) region is severely understudied despite the region's increase in new HIV infections since 2010. A key population that is particularly affected, due to the lack of adequate knowledge and proper interventional implementation, includes people who inject drugs (PWID). Furthermore, the paucity of HIV data (prevalence and trends) worsens an already critical situation in this region. A scoping review was conducted to address the scarcity of information and to synthesize the available data on HIV prevalence rates within the key population of PWID throughout the MENA region. Information was sourced from major public health databases and world health reports. Of the 1864 articles screened, 40 studies discussed the various factors contributing to the under-reporting of HIV data in the MENA region among PWID. High and overlapping risk behaviors were cited as the most prevalent reason why HIV trends were incomprehensible and hard to characterize among PWID, followed by lack of service utilization, lack of intervention-based programs, cultural norms, lack of advanced HIV surveillance systems, and protracted humanitarian emergencies. Overall, the lack of reported information limits any adequate response to the growing and unknown HIV trends throughout the region.