De novo Drug Delivery Modalities for Treating Damaged Hearts: Current Challenges and Emerging Solutions

Cardiovascular disease (CVD) is the leading cause of mortality, resulting in approximately one-third of deaths worldwide. Among CVD, acute myocardial infarctions (MI) is the leading cause of death. Current treatment modalities for treating CVD have improved over the years, but the demand for new and innovative therapies has been on the rise. The field of nanomedicine and nanotechnology has opened a new paradigm for treating damaged hearts by providing improved drug delivery methods, specifically targeting injured areas of the myocardium. With the advent of innovative biomaterials, newer therapeutics such as growth factors, stem cells, and exosomes have been successfully delivered to the injured myocardial tissue, promoting improvement in cardiac function. This review focuses on three major drug delivery modalities: nanoparticles, microspheres, and hydrogels, and their potential for treating damaged hearts following an MI.

ASSESSMENT OF DRUG USE FOR INPATIENTS WHO WERE PRESCRIBED CEFTAZIDIME: A RETROSPECTIVE CROSS-SECTIONAL STUDY IN A DISTRICT-LEVEL HOSPITAL

In health facilities, there is a lot of public concern about the irrational use of medications, especially antibiotic misuse. This retrospective cross-sectional study was conducted to assess the utilization of medicines for inpatients using ceftazidime in treatment in a district-level hospital in Vietnam, using 396 medical records. The results showed that there were approximately 6.7 kinds of drugs prescribed for each inpatient, including roughly 1.23 antibiotics. On average, 5.69 days of hospitalization cost an inpatient about 74.31USD, including more than 20USD for medicines (9.22USD for antibiotics) and 54.27USD for other expenses. There were 19.70% of medical records in which found at least one drug-drug interaction. Cardiovascular medicines, corticoids, fluoroquinolones and proton-pump inhibitors were medicine groups involving many found drug-drug interactions. For ceftazidime, indications of this antibiotic were inappropriate for nearly half of inpatients. For 199 inpatients whose indications’ ceftazidime were appropriate, the route of ceftazidime administration was appropriate but its dose per day and dose duration were inappropriate. More importantly, ceftazidime was used with a dosage lower than the recommended dosage (98.99%). In conclusion, there were several problems involving drug use that should be addressed, including curbing major drug-drug interactions and the irrational use of ceftazidime, a watch-group, broad-spectrum antibiotic.

Drug offence detection during the pandemic: a spatiotemporal study of drug markets

Research on COVID-19 and crime has so far shown that most crime types declined, especially in the early months of the pandemic. Illicit drug offences were a notable exception, however few studies have considered changes at specific drug market locations. This study documents how key drug markets were affected during the lockdown. Using a spatiotemporal generalised additive model (GAM), this study examines the pattern of drug offence detection throughout the city of Brisbane, Australia and identifies areas of change during lockdown. Statistical meshblock analysis is used to illustrate discrete changes at key market locations. Contrary to aggregate-level analysis, we show that several of the major drug markets experienced a significant decline in drug offence detections, but that these local changes were offset by a displacement to neighbouring areas. We also find some preliminary evidence of the emergence of new outer-urban markets. Existing drug markets were adversely affected by the COVID-19 lockdown, however drug market activity was likely displaced rather than diminished.

High levels of used syringe use and unsafe sex among people who inject drugs in Kumasi, Ghana: an urgent call for a comprehensive harm reduction approach

Background Drug use is a growing concern in Ghana. People who inject drugs (PWID) are highly vulnerable to HIV and other infectious diseases. Ghana’s National Strategic Plan for HIV/AIDS 2016–2020 identifies PWID as a key population, but efforts to address the needs of PWID have lagged behind those targeting sex workers and men who have sex with men. Lack of information about PWID is a critical barrier to implementing effective HIV prevention and treatment. We aimed to learn more about the vulnerability of the PWID population in order to inform much-needed harm reduction interventions. Methods From April to July 2018, we conducted a mixed methods study in Kumasi, Ghana, to identify all major drug using locations, count the numbers of PWID to obtain rough population size estimations, and administer anonymous surveys to 221 PWID regarding drug use and sexual behavior. We also tested for HIV, HCV, and HBV from syringes used by survey participants. Results Key informants identified five major drug using locations and estimated the total PWID population size to be between 600 and 2000. Enumerators counted between 35 and 61 individuals present at each of the five bases. Sharing syringes and reusing discarded syringes are common practices. Over half of survey participants (59%) reported past-month syringe sharing (34% used a used syringe and 52% gave away a used syringe). Individuals with higher injection frequency (≥ 21 times weekly) and who injected with four or more people had higher odds of syringe sharing. Of the survey participants reporting sex in the last month (23%), most reported having one partner, but only 12% used condoms. Nearly all women (11/13) reported exchanging sex for drugs and 6/13 reported exchanging sex for money in the last six months. Fifteen percent of participants (all men) reported paying for sex using drugs or money. Of the used syringes, prevalence estimates were 3% (HIV), 2% (HCV), and 9% (HBV). Conclusions Our findings confirm the urgent need to implement harm reduction interventions targeting PWID and to build a strong and enabling legal and policy environment in Ghana to support these efforts.

Interactions in cancer treatment considering cancer therapy, concomitant medications, food, herbal medicine and other supplements

Purpose The aim of our study was to analyse the frequency and severity of different types of potential interactions in oncological outpatients’ therapy. Therefore, medications, food and substances in terms of complementary and alternative medicine (CAM) like dietary supplements, herbs and other processed ingredients were considered. Methods We obtained data from questionnaires and from analysing the patient records of 115 cancer outpatients treated at a German university hospital. Drug–drug interactions were identified using a drug interaction checking software. Potential CAM-drug interactions and food–drug interactions were identified based on literature research. Results 92.2% of all patients were at risk of one or more interaction of any kind and 61.7% of at least one major drug–drug interaction. On average, physicians prescribed 10.4 drugs to each patient and 6.9 interactions were found, 2.5 of which were classified as major. The most prevalent types of drug–drug interactions were a combination of QT prolonging drugs (32.3%) and drugs with a potential for myelotoxicity (13.4%) or hepatotoxicity (10.1%). In 37.2% of all patients using CAM supplements the likelihood of interactions with medications was rated as likely. Food-drug interactions were likely in 28.7% of all patients. Conclusion The high amount of interactions could not be found in literature so far. We recommend running interaction checks when prescribing any new drug and capturing CAM supplements in medication lists too. If not advised explicitly in another way drugs should be taken separately from meals and by using nonmineralized water to minimize the risk for food–drug interactions.

GRK2/3/5/6 knockout: The impact of individual GRKs on arrestin-binding and GPCR regulation

G protein-coupled receptors (GPCRs) comprise the largest family of transmembrane receptors and represent major drug targets. Upon ligand stimulation, GPCRs activate G proteins and undergo a complex regulation by interaction with GPCR kinases (GRKs) and formation of receptor–arrestin complexes. For many GPCRs, this mechanism triggers receptor desensitisation, internalisation, and possibly a second intracellular signalling wave. Here we created eleven different HEK293 knockout cell clones for GRK2, 3, 5, and 6 individually and in combination. These include four single, two double, four triple, and the quadruple GRK knockout. The statistical evaluation of β-arrestin1/2 interactions for twelve different receptors grouped the tested GPCRs into two main subsets: those for which β-arrestin interaction was mediated by either GRK2, 3, 5, or 6 and those that are mediated by GRK2 or 3 only. Interestingly, the overexpression of specific GRKs was found to induce a robust, ligand-independent β-arrestin interaction with the V2R and AT1R. Finally, using GRK knockout cells, PKC inhibitors, and β-arrestin mutants, we present evidence for differential AT1R–β-arrestin2 complex configurations mediated by selective engagement of PKC, GRK2, or GRK6. We anticipate our novel GRK-knockout platform to facilitate the elucidation of previously unappreciated details of GRK-specific GPCR regulation and β-arrestin complex formation.

Strategies to Target ADAM17 in Disease: From Its Discovery to the iRhom Revolution

For decades, disintegrin and metalloproteinase 17 (ADAM17) has been the object of deep investigation. Since its discovery as the tumor necrosis factor convertase, it has been considered a major drug target, especially in the context of inflammatory diseases and cancer. Nevertheless, the development of drugs targeting ADAM17 has been harder than expected. This has generally been due to its multifunctionality, with over 80 different transmembrane proteins other than tumor necrosis factor α (TNF) being released by ADAM17, and its structural similarity to other metalloproteinases. This review provides an overview of the different roles of ADAM17 in disease and the effects of its ablation in a number of in vivo models of pathological conditions. Furthermore, here, we comprehensively encompass the approaches that have been developed to accomplish ADAM17 selective inhibition, from the newest non-zinc-binding ADAM17 synthetic inhibitors to the exploitation of iRhom2 to specifically target ADAM17 in immune cells.

Bacteriophage Therapy of Bacterial Infections: The Rediscovered Frontier

Antibiotic-resistant infections present a serious health concern worldwide. It is estimated that there are 2.8 million antibiotic-resistant infections and 35,000 deaths in the United States every year. Such microorganisms include Acinetobacter, Enterobacterioceae, Pseudomonas, Staphylococcus and Mycobacterium. Alternative treatment methods are, thus, necessary to treat such infections. Bacteriophages are viruses of bacteria. In a lytic infection, the newly formed phage particles lyse the bacterium and continue to infect other bacteria. In the early 20th century, d’Herelle, Bruynoghe and Maisin used bacterium-specific phages to treat bacterial infections. Bacteriophages are being identified, purified and developed as pharmaceutically acceptable macromolecular “drugs,” undergoing strict quality control. Phages can be applied topically or delivered by inhalation, orally or parenterally. Some of the major drug-resistant infections that are potential targets of pharmaceutically prepared phages are Pseudomonas aeruginosa, Mycobacterium tuberculosis and Acinetobacter baumannii.