15 research outputs found
Formulation, stabilisation and encapsulation of bacteriophage for phage therapy
Against a backdrop of global antibiotic resistance and increasing awareness of the importance of the
human microbiota, there has been resurgent interest in the potential use of bacteriophages for
therapeutic purposes, known as phage therapy. A number of phage therapy phase I and II clinical
trials have concluded, and shown phages don’t present significant adverse safety concerns. These
clinical trials used simple phage suspensions without any formulation and phage stability was of
secondary concern. Phages have a limited stability in solution, and undergo a significant drop in
phage titre during processing and storage which is unacceptable if phages are to become regulated
pharmaceuticals, where stable dosage and well defined pharmacokinetics and pharmacodynamics
are de rigueur. Animal studies have shown that the efficacy of phage therapy outcomes depend on
the phage concentration (i.e. the dose) delivered at the site of infection, and their ability to target and
kill bacteria, arresting bacterial growth and clearing the infection. In addition, in vitro and animal
studies have shown the importance of using phage cocktails rather than single phage preparations to
achieve better therapy outcomes. The in vivo reduction of phage concentration due to interactions
with host antibodies or other clearance mechanisms may necessitate repeated dosing of phages, or
sustained release approaches. Modelling of phage-bacterium population dynamics reinforces these
points. Surprisingly little attention has been devoted to the effect of formulation on phage therapy
outcomes, given the need for phage cocktails, where each phage within a cocktail may require
significantly different formulation to retain a high enough infective dose.
This review firstly looks at the clinical needs and challenges (informed through a review of key animal
studies evaluating phage therapy) associated with treatment of acute and chronic infections and the
drivers for phage encapsulation. An important driver for formulation and encapsulation is shelf life and
storage of phage to ensure reproducible dosages. Other drivers include formulation of phage for
encapsulation in micro- and nanoparticles for effective delivery, encapsulation in stimuli responsive
systems for triggered controlled or sustained release at the targeted site of infection. Encapsulation of
phage (e.g. in liposomes) may also be used to increase the circulation time of phage for treating
systemic infections, for prophylactic treatment or to treat intracellular infections. We then proceed to
document approaches used in the published literature on the formulation and stabilisation of phage for
storage and encapsulation of bacteriophage in micro- and nanostructured materials using freeze
drying (lyophilization), spray drying, in emulsions e.g. ointments, polymeric microparticles,
nanoparticles and liposomes. As phage therapy moves forward towards Phase III clinical trials, the
review concludes by looking at promising new approaches for micro- and nanoencapsulation of
phages and how these may address gaps in the field
Diabetes and Cardiovascular Care Among People with Severe Mental Illness: A Literature Review
Close to 19 million US adults have severe mental illnesses (SMI), and they die, on average, 25Â years earlier than the general population, most often from cardiovascular disease (CVD). Many of the antipsychotic medications used to treat SMI contribute to CVD risk by increasing risk for obesity, type 2 diabetes, dyslipidemia, and hypertension. Based on compelling evidence, the American Diabetes Association and the American Psychiatric Association developed guidelines for metabolic screening and monitoring during use of these medications. In this manuscript, we have reviewed the evidence on diabetes and other CVD risk screening, prevalence, and management among populations with SMI. We also review differences in screening among subpopulations with SMI (e.g., racial/ethnic minorities, women, and children). We found that despite national guidelines for screening for diabetes and other cardiovascular risk factors, up to 70Â % of people taking antipsychotics remain unscreened and untreated. Based on estimates that 20Â % of the 19 million US adults with SMI have diabetes and 70Â % of them are not screened; it is likely that over 2 million Americans with SMI have unidentified diabetes. Given that undiagnosed diabetes costs over 8 billion in annual preventable costs to our healthcare system. Given the high burden of disease and significant evidence of suboptimal medical care received by people with SMI, we propose several clinical and policy recommendations to improve diabetes and other CVD risk screening and care for this highly vulnerable population. These recommendations include reducing antipsychotic medication dose or switching antipsychotic medications, enhancing smoking cessation efforts, sharing electronic health records between physical and mental health care systems, and promoting integration of care