Liposome-based delivery of biological drugs

Biological drugs are attracting tremendous attention in disease treatment. However, their application is significantly limited by their inherent properties, such as high hydrophilicity, poor membranepermeability, low stability, and larger size. Liposome-based drug delivery systems are emerging as promising tools to improve their delivery, owing to their ability to reduce toxicity, improve bioavailability,and enhance the therapeutic efficacy of the drug by optimizing delivery to the specific target site. Here,we reviewed the types of liposomes and their applications as carriers for biological drugs to treat various diseases, emphasized the commercial products, and ultimately provided perspectives in this field.

Liver-side of inflammatory bowel diseases:Hepatobiliary and druginduced disorders

Hepatobiliary disorders are among the most common extraintestinal manifestations in inflammatory bowel diseases(IBD),both in Crohn’s disease and ulcerative colitis(UC),and therefore represent a diagnostic challenge.Immunemediated conditions include primary sclerosing cholangitis(PSC)as the main form,variant forms of PSC(namely small-duct PSC,PSC-autoimmune hepatitis overlap syndrome and IgG4-related sclerosing cholangitis)and granulomatous hepatitis.PSC is by far the most common,presenting in up to 8%of IBD patients,more frequently in UC.Several genetic foci have been identified,but environmental factors are preponderant on disease pathogenesis.The course of the two diseases is typically independent.PSC diagnosis is based mostly on typical radiological findings and exclusion of secondary cholangiopathies.Risk of cholangiocarcinoma is significantly increased in PSC,as well as the risk of colorectal cancer in patients with PSC and IBD-related colitis.No disease-modifying drugs are approved to date.Thus,PSC management is directed against symptoms and complications and includes medical therapies for pruritus,endoscopic treatment of biliary stenosis and liver transplant for end-stage liver disease.Other nonimmune-mediated hepatobiliary disorders are gallstone disease,whose incidence is higher in IBD and reported in up to one third of IBD patients,non-alcoholic fatty liver disease,pyogenic liver abscess and portal vein thrombosis.Druginduced liver injury(DILI)is an important issue in IBD,since most IBD therapies may cause liver toxicity;however,the incidence of serious adverse events is low.Thiopurines and methotrexate are the most associated with DILI,while the risk related to anti-tumor necrosis factor-αand anti-integrins is low.Data on hepatotoxicity of newer drugs approved for IBD,like anti-interleukin 12/23 and tofacitinib,are still scarce,but the evidence from other rheumatic diseases is reassuring.Hepatitis B reactivation during immunosuppressive therapy is a major concern in IBD,and adequate screening and vaccination is warranted.On the other hand,hepatitis C reactivation does not seem to be a real risk,and hepatitis C antiviral treatment does not influence IBD natural history.The approach to an IBD patient with abnormal liver function tests is complex due to the wide range of differential diagnosis,but it is of paramount importance to make a quick and accurate diagnosis,as it may influence the therapeutic management.

COVID-19: Considerations about immune suppression and biologicals at the time of SARS-CoV-2 pandemic

The extent of the profound immunological and nonimmunological responses linked to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection is currently being investigated worldwide due to the large burden associated with death due to SARS-CoV-2 and the short-term consequences of coronavirus disease 2019(COVID-19).It has been hypothesized that patients on immunosuppressive treatments,including biologics,may have an augmented risk of being infected by SARS-CoV-2;however,there are currently no definitive data about biological drugs and COVID-19 in immune-mediated inflammatory diseases.Current epidemiological models developed to understand how long the COVID-19 epidemic may last are not conclusive and range from sustained epidemics to complete elimination.Nevertheless,even in the best-case scenario of apparent elimination,there is concordance about a possible contagion resurgence as late as 2024.Therefore,knowledge of the impact of SARS-CoV-2 on immunemediated diseases and among patients treated with biologicals,together with the results of novel and promising COVID-19 treatment strategies targeting the virus and the host immune response(or both),will help us to best manage our patients during this pandemic over the next few years.

What is the best biological treatment for rheumatoid arthritis? A systematic review of effectiveness

AIM:To evaluate the effectiveness of the biological disease-modifying antirheumatic drugs(b DMARD) in the treatment of rheumatoid arthritis through a systematic review of observational studies.METHODS:The studies were searched in the Pub Med,EMBASE,Cochrane Controlled Trials Register and LILACS databases(until August 2014),in the grey literature and conducted a manual search.The assessed criteria of effectiveness included the EULAR,the disease activity score(DAS),the Clinical Disease Activity Index,the Simplified Disease Activity Index,the American College of Rheumatology and the Health Assessment Questionnaire.The meta-analysis was performed with Review Manager 5.2 software using a random effects model.A total of 35 studies were included in this review.RESULTS:The participants anti-tumor necrosis factor inhibitors(TNF) nave,who used adalimumab(P = 0.0002) and etanercept(P = 0.0006) exhibited greater good EULAR response compared to the participants who used infliximab.No difference was detected between adalimumab and etanercept(P = 0.05).The participants who used etanercept exhibited greater remission according to DAS28 compared to the participants who used infliximab(P = 0.01).No differences were detected between adalimumab and infliximab(P = 0.12) or etanercept(P = 0.79).Better results were obtained with b DMARD associated with methotrexate than with b DMARD alone.The good EULAR response and DAS 28 was better for combination with methotrexate than b DMARD monotherapy(P = 0.03 e P < 0.00001).In cases of therapeutic failure,the participants who used rituximab exhibited greater DAS28 reduction compared to those who used anti-TNF agents(P = 0.0002).The participants who used etanercept achieved greater good EULAR response compared to those who did not use that drug(P = 0.007).Studies that assessed reduction of the CDAI score indicated the superiority of abatacept over rituximab(12.4 vs +1.7) and anti-TNF agents(7.6 vs 8.3).The present systematic review with meta-analysis found that relative to anti-TNF treatmentnave patients,adalimumab and etanercept were more effective when combined with methotrexate than when used alone.Furthermore,in case of therapeutic failure with anti-TNF agents;rituximab and abatacept(non anti-TNF) and etanercept(as second anti-TNF) were more effective.However,more studies of effectiveness were found for the rituximab.CONCLUSION:The best treatment for treatment-nave patients is adalimumab or etanercept combined with methotrexate.For anti-TNF therapeutic failure,the best choice is rituximab,abatacept or etanercept.

New Progress in the Treatment of Myasthenia Gravis

In recent decades, the treatment of myasthenia gravis has been extensively developed, but a standardized standard still needs to be used. Its treatment strategy is associated with patient prognosis, economic costs, and complications. This article reviews the pathogenesis, treatment methods, and complications of myasthenia gravis, providing new ideas for diagnosing and treating myasthenia gravis and fully embodies the principle of safety and precision.

Constructive strategies for drug delivery systems in antivirus disease therapy by biosafety materials

Due to the coronavirus disease 2019(COVID‐19)pandemic,the development of antiviral drugs has attracted increasing attention.Clinical antiviral drugs show weak solubility,low bioavailability,adverse side effects,or only limited targets.With the advancement of nanotechnology and material science,biosafety nanomaterials have been constructed for drug delivery systems of antiviral disease therapy,such as liposomes,polymers,gold nanoparticles,and graphene.These nanodrug systems can either deliver synthesized antiviral drugs siRNA/miRNA and small molecular compounds,deliver bioactive large molecular drug proteins and mRNA,or show antiviral activity by themselves.Nanodelivery systems could effectively enhance the efficiency of antiviral drugs by increasing drug loading and host cell uptake with a small size and high specific surface area.This review focused on the biosafety nanomaterials used for antiviral therapy and discussed the options for the design of antiviral drugs in the future.