study of the blood-brain barrier transport of bioactives from Mediterranean foods.

The Mediterranean diet (MD), characterized by olive oil, olives, fruits, vegetables, and wine intake, is associated with a reduced risk of dementia. These foods are rich in bioactives with neuroprotective and antioxidant properties, including hydroxytyrosol (HT), tyrosol (TYRS), serotonin (SER) and protocatechuic acid (PCA), a phenolic acid metabolite of anthocyanins. It remains to be established if these molecules cross the blood-brain barrier (BBB), a complex interface that strictly controls the entrance of molecules into the brain.

MEF2C and miR-194-5p: New Players in Triple Negative Breast Cancer Tumorigenesis.

Among breast cancer (BC) subtypes, the most aggressive is triple negative BC (TNBC), which is prone to metastasis. We previously found that microRNA (miR)-194-5p is downregulated at the early stages of TNBC brain metastasis development. Additionally, the transcription factor myocyte enhancer factor 2 (MEF2)C, a bioinformatically predicted miR-194-5p target, was increasingly expressed throughout TNBC brain metastasis formation and disease severity.

Development of fast dissolving polymer-based microneedles for delivery of an antigenic melanoma cell membrane.

Delivery of cancer cell membranes (CM) is a new approach for the activation of the immune system and the induction of immunotherapy of cancer. Local delivery of melanoma CM into skin can induce efficient immune stimulation of antigen presenting cells (APCs), such as dendritic cells. In the current study, fast dissolving microneedles (MNs) were developed for the delivery of melanoma B16F10 CM.

Rapid, multiplex detection of SARS-CoV-2 using isothermal amplification coupled with CRISPR-Cas12a.

In December 2019 an outbreak erupted due to the beta coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 in Wuhan, China. The disease caused by this virus (COVID-19) rapidly spread to all parts of the globe leading to a global pandemic. Efforts to combat the pandemic rely on RT-qPCR diagnostic tests that have high turnaround times (~ 24 h), are easily contaminated, need specialized equipment, facilities, and personnel that end up increasing the overall costs of this method.

A Drug Screening Reveals Minocycline Hydrochloride as a Therapeutic Option to Prevent Breast Cancer Cells Extravasation across the Blood-Brain Barrier.

Among breast cancer (BC) patients, 15-25% develop BC brain metastases (BCBM), a severe condition due to the limited therapeutic options, which points to the need for preventive strategies. We aimed to find a drug able to boost blood-brain barrier (BBB) properties and prevent BC cells (BCCs) extravasation, among PI3K, HSP90, and EGFR inhibitors and approved drugs. We used BCCs (4T1) and BBB endothelial cells (b.

Critical appraisal and future outlook on anti-inflammatory biosimilar use in chronic immune-mediated inflammatory diseases.

Biosimilars represent a novel category in the world of follow-up medicinal products with the requirement that they are highly similar but not identical to an approved originator biologic medicine, with no clinically meaningful differences in safety, purity, and potency. In this review, we discuss recent pivotal biosimilar developments for anti-inflammatory therapy in rheumatology, gastroenterology, and dermatology, and the influence of biosimilar availability on patients and payers. Finally, we provide our perspective on the evolution of biosimilar use in these indications in the United States (US) and in Europe and on where this evolution in biopharmaceuticals may lead in the future.

Biosimilars in an era of rising oncology treatment options.

New diagnostic technologies, including molecular profiling, have enabled advances in treatments of various cancers; this has significantly improved clinical outcomes, including overall survival. However, the high cost of biologic drugs may prevent patients from having access to optimal treatment. Introduction of lower priced biosimilar agents into the therapeutic armamentarium brings the potential to ease the burden on healthcare expenditure and facilitate better access to effective cancer treatments.

Laser diffraction as a powerful tool for amorphous solid dispersion screening and dissolution understanding.

Biopharmaceutics Classification System (BCS) class II and IV drugs may be formulated as supersaturating drug delivery systems (e.g., amorphous solid dispersions [ASDs]) that can generate a supersaturated drug solution during gastrointestinal (GI) transit.

Understanding and Minimising Injection-Site Pain Following Subcutaneous Administration of Biologics: A Narrative Review.

Injection-site pain (ISP) is a subjective side effect that is commonly reported with the subcutaneous administration of biological agents, yet it may only be a concern to some. Multiple factors related to the product formulation, such as pH, volume and excipients, and/or to the injection process have the potential to contribute to ISP, while patient-related factors, such as low body weight, gender and age, can make an individual more susceptible to experiencing ISP. While total elimination of ISP remains unlikely with any subcutaneously administered agent, it can be minimised by helping the patient to develop a confident and competent injection technique via robust and effective training.

Correction to: Immunogenicity of Biosimilars for Rheumatic Diseases, Plaque Psoriasis, and Inflammatory Bowel Disease: A Review from Clinical Trials and Regulatory Documents.

The article Immunogenicity of Biosimilars for Rheumatic Diseases, Plaque Psoriasis, and Inflammatory Bowel Disease: A Review from Clinical Trials and Regulatory Documents, written by Vibeke Strand, Joao Gonçalves, Timothy P. Hickling, Heather E. Jones, Lisa Marshall and John D.

SB5 shows cross-immunogenicity to adalimumab but not infliximab: results in patients with inflammatory bowel disease or rheumatoid arthritis.

Background: The primary objective of this study was to analyze the cross-reactivity of antidrug antibodies to reference adalimumab (ADL) and SB5 (adalimumab biosimilar) in patients with inflammatory bowel disease (IBD) or rheumatoid arthritis (RA).

Methods: Sera from patients with IBD and RA with or without antibodies to adalimumab (ATA+ or ATA-, respectively) were tested for cross-reactivity with SB5 and ADL. Functional inhibition of tumor necrosis factor-α binding was measured.

Therapeutic Antibody Engineering and Selection Strategies.

Antibody drugs became an increasingly important element of the therapeutic landscape. Their accomplishment has been driven by many unique properties, in particular by their very high specificity and selectivity, in contrast to the off-target liabilities of small molecules (SMs). Antibodies can bring additional functionality to the table with their ability to interact with the immune system, and this can be further manipulated with advances in antibody engineering.

Efficacy, immunogenicity and cost analysis of a systematic switch from originator infliximab to biosimilar CT-P13 of all patients with inflammatory arthritis from a single center.

Biosimilar drugs are intended to be as effective as the originator product but with a lower cost to healthcare systems. In our center we promoted a switch from originator infliximab (IFXor) to biosimilar infliximab (CT-P13). We analyzed efficacy, safety, immunogenicity and cost savings of switching.

Immunogenicity of Biosimilars for Rheumatic Diseases, Plaque Psoriasis, and Inflammatory Bowel Disease: A Review from Clinical Trials and Regulatory Documents.

The goal of this narrative review was to summarize immunogenicity data of biosimilars or biosimilar candidates for rheumatic diseases, plaque psoriasis, or inflammatory bowel disease (IBD), available in peer-reviewed publications or regulatory documents. PubMed records and regulatory documents were searched for immunogenicity data of TNFα or CD20 inhibitor biosimilars or biosimilar candidates. Data collected included the proportion of patients positive for anti-drug antibodies (ADAbs), proportion with neutralizing antibodies (nAbs) among ADAb-positive patients, ADAb/nAb assay characteristics, cross-reactivity, and the effects of ADAbs on pharmacokinetics, pharmacodynamics, efficacy, and safety.

Biosimilars in rheumatology.

Biotechnologicals are an invaluable resource in the treatment of patients with inflammatory rheumatic diseases (IRD) non-responsive or intolerant to conventional therapies. However, they are the main driver for increase in direct costs and represent a significant economic burden to healthcare systems worldwide. Since biosimilars are similar and more affordable versions of previously licenced biotechnologicals, they are expected to contribute to healthcare system sustainability and reduce inequities in treatment access.

Era of biosimilars in rheumatology: reshaping the healthcare environment.

Compared with the original approved biological drug on which it is based, a biosimilar has highly similar physicochemical characteristics and biological activity, as well as equivalent efficacy and no clinically meaningful differences in safety and immunogenicity. Before they are approved, biosimilars must undergo a rigorous development process using state-of-the-art technologies to establish biosimilarity to the reference biological product. After approval, biosimilars must comply with good pharmacological practices for biological drugs.

Anti-TNF biosimilars in psoriasis: from scientific evidence to real-world experience.

Tumor necrosis factor (TNF) inhibitors account for a large proportion of drugs used to treat psoriasis and are indicated first-line options in certain settings. Several biosimilar drugs based on the anti-TNF agents adalimumab, infliximab, and etanercept are now available for use in patients with psoriasis. The favorable cost differential of biosimilars is expected to improve access to biologic therapy for biologic-naive psoriasis patients, who are often undertreated.

Blood Supply to the Integument of the Abdomen of the Rat: A Surgical Perspective.

Background: Many fundamental questions regarding the blood supply to the integument of the rat remain to be clarified, namely the degree of homology between rat and humans. The aim of this work was to characterize in detail the macro and microvascular blood supply to the integument covering the ventrolateral aspect of the abdominal wall of the rat.

Methods: Two hundred five Wistar male rats weighing 250-350 g were used.

The changing landscape of biosimilars in rheumatology.

Biosimilars remain a hot topic in rheumatology, and some physicians are cautious about their application in the real world. With many products coming to market and a wealth of guidelines and recommendations concerning their use, there is a need to understand the changing landscape and the real clinical and health-economic potential offered by these agents. Notably, rheumatologists will be at the forefront of the use of biosimilar monoclonal antibodies/soluble receptors.

Biosimilar DMARDs: What Does the Future Hold?

Biological medicinal products, albeit fundamental in unresponsive inflammatory rheumatic diseases, represent a significant economic burden to healthcare systems worldwide. A new landmark in the treatment of these conditions was achieved with the European Medicines Agency's endorsement of CT-P13, the first biosimilar of a monoclonal antibody, infliximab. The main driving force behind biosimilar development is to improve accessibility at lower costs, provided the quality, efficacy and safety of the biosimilar is similar to that of the reference drug.

Screening methodologies for the development of spray-dried amorphous solid dispersions.

Purpose: To present a new screening methodology intended to be used in the early development of spray-dried amorphous solid dispersions.

Methods: A model that combines thermodynamic, kinetic and manufacturing considerations was implemented to obtain estimates of the miscibility and phase behavior of different itraconazole-based solid dispersions. Additionally, a small-scale solvent casting protocol was developed to enable a fast assessment on the amorphous stability of the different drug-polymer systems.

Analysis of cocaine and nicotine metabolites in wastewater by liquid chromatography-tandem mass spectrometry. Cross abuse index patterns on a major community.

A method based on sample preparation by solid phase extraction and analysis by liquid chromatography and mass spectrometry was validated and used for simultaneous analysis of cocaine, benzoylecgonine and cotinine in samples collected at the major wastewater treatment plant in the city of Lisbon. The aim was to estimate the consumption of both cocaine and nicotine in this community and establish an index involving both drugs supported by the relevance of nicotine as a significant anthropogenic marker. The study was made on two different weekdays during a month in order to evaluate patterns of consumption outside weekends.

Alginate films containing Lactobacillus plantarum as wound dressing for prevention of burn infection.

The topical application of lactobacilli is receiving attention for the prevention of superficial skin and burn wound infections. We studied the properties of Lactobacillus plantarum immobilized in calcium alginate films and investigated the antibacterial activity of these films in a model burn wound in rats. A multiresistant clinical isolate, VIM-2-metallo-β-lactamase-producing Pseudomonas aeruginosa, was used as the indicator strain.