Ticagrelor versus clopidogrel for recurrent myocardial infarction: An outcomes-based agreement.

Background: Outcomes-based agreements (OBA) are performance-based risk-sharing agreements between manufacturers and payers which provide the opportunity for collection and evaluation of real-world outcomes to supplement clinical trials.

Objectives: To describe an OBA comparing ticagrelor to clopidogrel in patients admitted with acute coronary syndrome (ACS) and proportion of recurrent myocardial infarction (MI) in a real-world setting.

Methods: Commercial (CM) and Medicare (MC) insurance patients of a large regional health plan, who presented with ACS and were prescribed either ticagrelor or clopidogrel were prospectively analyzed.

Elaborate biologic approval process delays care of patients with moderate-to-severe asthma.

Background: mAbs (biologics) are indicated in patients with poorly controlled moderate-to-severe asthma. The process of prior authorization and administration of a biologic requires exceptional commitment from clinical teams.

Objective: Our aim was to evaluate the process of approval and administration of biologics for asthma and determine the most common reasons associated with denials of biologics and delays in administration.

Translating clinical evidence into value-based payment models: pooled analyses of innovative real-world outcomes agreements for ticagrelor in the United States.

Innovative value strategies for reimbursement of medications include value-based agreements (VBAs) between payers and pharmaceutical manufacturers, which have the potential to improve affordability and patient access to therapy, as well as lead to a reduction in downstream health events and associated medical costs. VBAs link payment for a medication to its performance in real-world clinical practice measured against prespecified outcomes that are aligned to existing evidence. Given its high prevalence, economic burden, and impact on mortality, cardiovascular disease (namely, coronary heart disease) represents an opportunity for VBAs to contribute to improved health outcomes and patient experiences while reducing or containing total medical costs.

Nanomedicine in Alzheimer's disease: Amyloid beta targeting strategy.

The treatment of Alzheimer's disease (AD) is up to today one of the most unsuccessful examples of biomedical science. Despite the high number of literature evidences detailing the multifactorial and complex etiopathology of AD, no cure is yet present on the market and the available treatments are only symptomatic. The reasons could be ascribed on two main factors: (i) lack of ability of the majority of drugs to cross the blood-brain barrier (BBB), thus excluding the brain for any successful therapy; (ii) lack of selectivity and specificity of drugs, decreasing the efficacy of even potent anti-AD drugs.

Hybrid nanoparticles as a new technological approach to enhance the delivery of cholesterol into the brain.

Restoration of the Chol homeostasis in the Central Nervous System (CNS) could be beneficial for the treatment of Huntington's Disease (HD), a progressive, fatal, adult-onset, neurodegenerative disorder. Unfortunately, Chol is unable to cross the blood-brain barrier (BBB), thus a novel strategy for a targeted delivery of Chol into the brain is highly desired. This article aims to investigate the production of hybrid nanoparticles composed by Chol and PLGA (MIX-NPs) modified with g7 ligand for BBB crossing.

Qualitative and semiquantitative analysis of the protein coronas associated to different functionalized nanoparticles.

Aim: The investigation on protein coronas (PCs) adsorbed onto nanoparticle (NP) surface is representing an open issue due to difficulties in detection and clear isolation of the adsorbed proteins. In this study, we investigated protocols able to isolate the compositions of PCs of three polymeric NPs.

Materials & Methods: Unfunctionalized NPs and two functionalized NPs were considered as proof-of-concept for the qualitative and semiquantitative analysis of both the corona levels (stably or weakly adsorbed coronas [SC/WC]) of these different nanocarriers.

Reduced plaque size and inflammation in the APP23 mouse model for Alzheimer's disease after chronic application of polymeric nanoparticles for CNS targeted zinc delivery.

A local dyshomeostasis of zinc ions in the vicinity of amyloid aggregates has been proposed in Alzheimer's disease (AD) due to the sequestration of zinc in senile plaques. While an increase in zinc levels may promote the aggregation of amyloid beta (Aβ), increased brain zinc might also be beneficial rescuing some pathological alterations caused by local zinc deficiency. For example, increased Aβ degradation by metalloproteinases, and a reduction in inflammation can be hypothesized.

Current Strategies for the Delivery of Therapeutic Proteins and Enzymes to Treat Brain Disorders.

Brain diseases and injuries are growing to be one of the most deadly and costly medical conditions in the world. Unfortunately, current treatments are incapable of ameliorating the symptoms let alone curing the diseases. Many brain diseases have been linked to a loss of function in a protein or enzyme, increasing research for improving their delivery.

Anticancer drug-loaded quantum dots engineered polymeric nanoparticles: Diagnosis/therapy combined approach.

Primary Effusion Lymphoma (PEL) is an HHV-8-related non Hodgkin lymphoma localized in body cavities (as pleural, peritoneal and pericardial) presenting lymphomatous effusion that, until now, lack of an effective therapy. Curcumin was reported to display pro-apoptotic effect via the inhibition of the JAK/STAT pathway, that is overexpressed in PEL cells, as consequence of virus infection. The administration of curcumin is severely restricted by its physicochemical properties, mainly its low solubility in biological fluid and consequently low bioavailability.

Novel Curcumin loaded nanoparticles engineered for Blood-Brain Barrier crossing and able to disrupt Abeta aggregates.

The formation of extracellular aggregates built up by deposits of β-amyloid (Aβ) is a hallmark of Alzheimer's disease (AD). Curcumin has been reported to display anti-amyloidogenic activity, not only by inhibiting the formation of new Aβ aggregates, but also by disaggregating existing ones. However, the uptake of Curcumin into the brain is severely restricted by its low ability to cross the blood-brain barrier (BBB).

Protein corona and nanoparticles: how can we investigate on?

Nanoparticles (NPs) represent one of the most promising tools for drug-targeting and drug-delivery. However, a deeper understanding of the complex dynamics that happen after their in vivo administration is required. Particularly, plasma proteins tend to associate to NPs, forming a new surface named the 'protein corona' (PC).

Apoferritin nanocage as streptomycin drug reservoir: Technological optimization of a new drug delivery system.

The aim of this study is to formulate and characterize streptomycin-loaded apoferritin nanoparticles (ApoStrep NPs) for their potential therapeutic use in bacterial resistant infections (i.e. tuberculosis).

Protein cage nanostructure as drug delivery system: magnifying glass on apoferritin.

New frontiers in nanomedicine are moving towards the research of new biomaterials. Apoferritin (APO), is a uniform regular self-assemblies nano-sized protein with excellent biocompatibility and a unique structure that affords it the ability to stabilize small active molecules in its inner core. Areas covered: APO can be loaded by applying a passive process (mainly used for ions and metals) or by a unique formulative approach based on disassemby/reassembly process.

Potential Use of Nanomedicine for Drug Delivery Across the Blood-Brain Barrier in Healthy and Diseased Brain.

The research of efficacious non-invasive therapies for the treatment of brain diseases represents a huge challenge, as people affected by disorders of the central nervous system (CNS) will significantly increase. Moreover, the blood-brain barrier is a key factor in hampering a number of effective drugs to reach the CNS. This review is therefore focusing on possible interventions of nanomedicine-based approaches in selected diseases affecting the CNS.

EXPLOITING THE VERSATILITY OF CHOLESTEROL IN NANOPARTICLES FORMULATION.

The biocompatibility of polymers, lipids and surfactants used to formulate is crucial for the safe and sustainable development of nanocarriers (nanoparticles, liposomes, micelles, and other nanocarriers). In this study, Cholesterol (Chol), a typical biocompatible component of liposomal systems, was formulated in Chol-based solid nanoparticles (NPs) stabilized by the action of surfactant and without the help of any other formulative component. Parameters as type (Solutol HS 15, cholic acid sodium salt, poly vinyl alcohol and Pluronic-F68), concentration (0.

Targeted Polymeric Nanoparticles for Brain Delivery of High Molecular Weight Molecules in Lysosomal Storage Disorders.

Lysosomal Storage Disorders (LSDs) are a group of metabolic syndromes, each one due to the deficit of one lysosomal enzyme. Many LSDs affect most of the organ systems and overall about 75% of the patients present neurological impairment. Enzyme Replacement Therapy, although determining some systemic clinical improvements, is ineffective on the CNS disease, due to enzymes' inability to cross the blood-brain barrier (BBB).

Nanoparticle transport across the blood brain barrier.

While the role of the blood-brain barrier (BBB) is increasingly recognized in the (development of treatments targeting neurodegenerative disorders, to date, few strategies exist that enable drug delivery of non-BBB crossing molecules directly to their site of action, the brain. However, the recent advent of Nanomedicines may provide a potent tool to implement CNS targeted delivery of active compounds. Approaches for BBB crossing are deeply investigated in relation to the pathology: among the main important diseases of the CNS, this review focuses on the application of nanomedicines to neurodegenerative disorders (Alzheimer, Parkinson and Huntington's Disease) and to other brain pathologies as epilepsy, infectious diseases, multiple sclerosis, lysosomal storage disorders, strokes.

Relationship between symptom change, relapse activity and disability progression in multiple sclerosis.

Background: Symptom changes may serve as a risk factor for relapse activity (RA) and disability progression (DP), which could facilitate multiple sclerosis (MS) treatment decisions.

Objective: To assess the relationship of symptom change with RA and DP.

Methods: We evaluated the relationship of symptom change with subsequent RA and DP using NARCOMS registry data reported over a five-year period.

PEGylated siRNA lipoplexes for silencing of BLIMP-1 in Primary Effusion Lymphoma: In vitro evidences of antitumoral activity.

Silencing of the B lymphocyte-induced maturation protein 1 (Blimp-1), a pivotal transcriptional regulator during terminal differentiation of B cells into plasma cells with siRNAs is under investigation as novel therapeutic approach in Primary Effusion Lymphoma (PEL), a HHV-8 related and aggressive B cell Lymphoma currently lacking of an efficacious therapeutic approach. The clinical application of small interfering RNA (siRNA) in cancer therapy is limited by the lack of an efficient systemic siRNA delivery system. In this study we aim to develop pegylated siRNA lipoplexes formed using the cationic lipid DOTAP and DSPE-PEG2000, capable to effectively stabilize anti-Blimp-1 siRNA and suitable for systemic administration.

Cholesterol-loaded nanoparticles ameliorate synaptic and cognitive function in Huntington's disease mice.

Brain cholesterol biosynthesis and cholesterol levels are reduced in mouse models of Huntington's disease (HD), suggesting that locally synthesized, newly formed cholesterol is less available to neurons. This may be detrimental for neuronal function, especially given that locally synthesized cholesterol is implicated in synapse integrity and remodeling. Here, we used biodegradable and biocompatible polymeric nanoparticles (NPs) modified with glycopeptides (g7) and loaded with cholesterol (g7-NPs-Chol), which per se is not blood-brain barrier (BBB) permeable, to obtain high-rate cholesterol delivery into the brain after intraperitoneal injection in HD mice.

Exploiting Bacterial Pathways for BBB Crossing with PLGA Nanoparticles Modified with a Mutated Form of Diphtheria Toxin (CRM197): In Vivo Experiments.

Drugs can be targeted to the brain using polymeric nanoparticles (NPs) engineered on their surface with ligands able to allow crossing of the blood-brain barrier (BBB). This article aims to investigate the BBB crossing efficiency of polymeric poly lactide-co-glycolide (PLGA) NPs modified with a mutated form of diphtheria toxin (CRM197) in comparison with the results previously obtained using PLGA NPs modified with a glycopeptide (g7-NPs). Different kinds of NPs, covalently coupled PLGA with different fluorescent probes (DY405, rhodamine-B base and DY675) and different ligands (g7 and CRM197) were tested in vivo to assess their behavior and trafficking.

Application of Polymeric Nanoparticles for CNS Targeted Zinc Delivery In Vivo.

A dyshomeostasis of zinc ions has been reported for many psychiatric and neurodegenerative disorders including schizophrenia, attention deficit hyperactivity disorder, depression, autism, Parkinson's and Alzheimer's disease. Furthermore, alterations in zinc-levels have been associated with seizures and traumatic brain injury. Thus, altering zinclevels within the brain is emerging as a new target for the prevention and treatment of psychiatric and neurological diseases.