Formulation of Biologics for Alternative Routes of Administration: Current Problems and Perspectives

Introduction: Biologics (biopharmaceuticals) present new promising therapies for many diseases such as cancers, chronical inflammatory diseases and today's biggest challenge - COVID-19. Research: Today, most biologics have been synthetized using modern methods of biotechnology, in particular DNA recombinant technology. Current pharmaceutical forms of protein/peptide biopharmaceuticals are intended for parenteral route of administration due to their instability and large size of molecules. In order to improve patient compliance, many companies are working on developing adequate forms of biopharmaceuticals for alternative, non-invasive routes of administration. The aim of this work is to review current aspirations and problems in formulation of biopharmaceuticals for alternative (non-parenteral) routes of administration and to review the attempts to overcome them. These alternative routes of administration could be promising in prevention and treatment of COVID-19, among other serious diseases. Conclusion(s): The emphasis is on stabilizing monoclonal antibodies into special formulations and delivery systems;their application should be safer, more comfortable and reliable. When it comes to hormones, vaccines and smaller peptides, some companies have already registered drugs intended for nasal and oral delivery.Copyright © 2022 Sciendo. All rights reserved.

The school environment-related predictors of fights and bullying among School-Age Children in Serbia : Milena Šantrić Milićević

Background The health and development of school-age children is a contemporary topic of various health policies and programs, which has become even more of a focus in critical situations such as the COVID-19 pandemic. The study aims to assess the prevalence of school-age children's participation in fights and bullying in Serbia, and to examine the relevance of students’ socio-demographic characteristics and perceptions of school and relations with other students and professors for participation in fights and bullying. Methods A secondary analysis of the original data of the 2017 HBSC study is performed on 3267 students in a nationally representative sample of primary and high schools in Serbia. Predictors of taking part in fights and taking part in bullying were examined by using univariate and multivariate logistic regression. Results The main results show that 50.8% of boys and 17.1% of girls have taken part in fights, while 17.7% boys and 10.4% of girls have taken part in bullying. Students who felt a large and very large burden of school obligations were 1.43 times more likely to participate in bullying at least once, while they were 1.38 and 2.12 times more likely to participate in multiple fights and 4.04, 1.24, and 2.78 times more likely to participate multiple times in bullying. Fights among school-age children are significantly positively associated with living with relatives/legal guardians and poor quality of life. Conclusions The prevalence of participating in at least one fight/bullying is higher than in multiple fights/bullying. These associations suggest a necessity to enhance the monitoring and control of peer behavior among school-age children. The findings of the study imply key enablers of protection, such as building relationships based on team spirit and work, friendly behavior, empathy, and help, which should be included in the value system of school and family activities in programs to combat fights and bullying in school-age children. Key messages • In Serbia, every second boy and every fifth girl participated in fights, while less than every fifth boy and every tenth girl participated in bullying. • Study results can inform school and healthcare actors’ efforts to improve school-age children’s development and health capacity for life.

Refractory myasthenic crisis in a patient with refractory Myasthenia gravis and COVID-19

Background and aims: Myasthenia gravis (MG) is an autoimmune, antibody-mediated disease of the neuromuscular junction causing muscle weakness. Due to immunosuppression and possible respiratory/bulbar muscle weakness, MG patients are at risk for developing severe coronavirus disease 2019 (COVID-19). Methods: Case report. Results: A 62years old patient suffered from bulbar onset generalized MG with acetylcholine receptor antibodies since eight months. He survived two prior MC and was nourished via percutaneous enterogastrostomy (PEG) despite symptomatic treatment and immunosuppression with azathioprine and steroids (severity graded according Myasthenia gravis foundation of America score (MGFA) IVb). He presented with fever, cough and severe generalised muscle weakness. Polymerase chain reaction confirmed COVID-19, ventilatory failure prompted mechanical ventilation (MV). Intravenous immunoglobulins (ivIg) and pyridostigmine i.v. were given. Weaning had to be postponed because of respiratory muscle weakness and septicaemia with Enterobacter cloacae, treated with appriopriate antibiotics. Not until removal of PEG sepsis resolved and plasmapheresis (PLEX) was conducted. The patient reached spontaneous breathing via tracheostomy, but still needed nasogastric tube feeding (MGFA V). Because of missing further progress of bulbar muscle function complement inhibition with eculizumab was administered (900mg 1 x weekly for four weeks, thereafter 1200mg every two weeks). After the second dose tracheostomy and nasogastric tubes could be removed, bulbar and generalized weakness resolved on follow-up (MGFA IIa). Conclusion: Our patient experienced MC triggered by COVID-19 and suffered from prolonged sepsis. After failure of standard treatments (IvIg/PLX) eculizumab was given, followed by marked recovery. The role of complement inhibition for treatment of refractory myasthenic crises should be further studied.