Drugs based on peptides and proteins (PPs) have been widely used in medicine, beginning with insulin therapy in patients with diabetes mellitus over a century ago. Although the oral route of drug administration is the preferred one by the vast majority of patients and improves compliance, medications of this kind due to their specific chemical structure are typically delivered parenterally, which ensures optimal bioavailability. In order to overcome issues connected with oral absorption of PPs such as their instability depending on digestive enzymes and pH changes in the gastrointestinal (GI) system on the one hand, but also their limited permeability across physiological barriers (mucus and epithelium) on the other hand, scientists have been strenuously searching for novel delivery methods enabling peptide and protein drugs (PPDs) to be administered enterally. These include utilization of different nanoparticles, transport channels, substances enhancing permeation, chemical modifications, hydrogels, microneedles, microemulsion, proteolytic enzyme inhibitors, and cell-penetrating peptides, all of which are extensively discussed in this review. Furthermore, this article highlights oral PP therapeutics both previously used in therapy and currently available on the medical market.

Hypercholesterolemia plays a crucial role in the development of atherosclerosis, but it remains an undertreated and underdiagnosed disease. Taking into consideration the high prevalence of lipid disorders, long duration of the asymptomatic course of the disease, life-threatening complications resulting from inaccurate therapy, and stringent treatment goals concerning LDL cholesterol level in the prevention of cardiovascular events, novel lipid-lowering therapies have been introduced in the last few years. In this article, a drug belonging to the group of small interfering RNA (siRNA) called inclisiran is described. It is a novel molecule that increases the number of LDL receptors (LDLRs) on the surface of hepatic cells by preventing the formation of proprotein convertase subtilisin/kexin type 9 (PCSK9) responsible for the degradation of LDLRs. With great potential for lowering plasma LDL cholesterol level, high liver specificity, comfortable dosing regimen, and good tolerance without significant adverse effects, it could play an important part in future hypolipemic therapies.

Introduction: Patients with asthma have a higher incidence of allergic or nonallergic persistent rhinitis, and chronic rhinosinusitis with or without nasal polyps. The nasal symptoms significantly reduce quality of life and substantially affect the asthma control among these patients. Because of no complete knowledge of the etiology of rhinological symptoms, in some patients the proposed therapeutic options are still ineffective. Recommended pharmacotherapy, immunotherapy, and surgical treatment do not have the expected therapeutic effect in some patients. More recently, biological treatment based on phenotyping has become a new alternative therapeutic option. Currently, omalizumab, a monoclonal antibody with an anti-IgE effect in patients with allergic phenotypes or mepolizumab, an anti-IL-5 biologic that reduces the number of eosinophils, may be used. Methods: In this single-center, real-live study, authors analyzed effects of biological treatment on rhinological symptoms in patients over the age of 18 with severe uncontrolled bronchial asthma with coexisting persistent allergic rhinitis treated with omalizumab or uncontrolled bronchial asthma with coexisting chronic rhinosinusitis with nasal polyps treated with mepolizumab. In all patients, the otolaryngologist performed anterior rhinoscopy. Evaluation of rhinological symptoms and quality of life in patients treated with anti-IgE or anti-IL5 therapy before and 6 months after biological treatment was performed using the TNSS and SNOT-22 scales. The sub-analysis of changes in rhinological symptoms was also performed in a group of patients with N-ERD regardless of eosinophilic or allergic asthma phenotype. Results: A total of 48 patients (9 male, 18%) with severe chronic bronchial asthma treated with biologics were included into the study. Among them, there were 26 (54%) patients with allergic asthma and persistent allergic rhinitis treated with omalizumab, and 22 (46%) with eosinophilic asthma and chronic rhinosinusitis with nasal polyps treated with mepolizumab. In both groups, 6 months of treatment with omalizumab or mepolizumab resulted in significant improvement in relation to all rhinological symptoms assessed with TNSS and SNOT-22 scales. There was a significant increase in the number of patients with smell improvement in the mepolizumab-treated group. Improvements in all rhinitis symptoms and quality of life assessed by TNSS and SNOT-22 scales after 6 months of treatment were comparable in NSAIDs-sensitive versus NSAIDs-tolerant patients regardless of type of monoclonal antibodies used. Conclusion: Six-month phenotyping-based biological therapy with omalizumab in patients with chronic allergic rhinitis accompanied by several bronchial asthma or with mepolizumab in patients with chronic sinusitis with nasal polyps accompanied by several bronchial asthma showed significant improvement in rhinological symptoms and quality of life.

Introduction: Vitamin K, discovered in the 1930s, is a very important compound for the human body, performing many functions. The most well known of them are calcium homeostasis and coagulation. Nowadays it is apparent that many more beneficial multiorgan aspects of vitamin K exist. The aim of the study was to review the properties of vitamin K and to show its potential therapeutic value. Materials and methods: Medline databases (PubMed) and other scientific sources were searched. Results: Vitamin K shows a multifaceted effect on the proper functioning of the human body: preventing coronary vessel calcification, maintains normal blood pressure, has neuroprotective effects, reduces the risk of myocardial infarction, slows the process of osteoclastogenesis, and influences the production of bone reabsorption factors. In addition, vitamin K supplementation has been shown to reduce the risk of hepatocellular carcinoma (HCC) by interfering with tumour cells cycle and inducing their apoptosis. The pro-apoptotic activity of menaquinone is not limited to HCC only, but also to other cancers such as glioblastoma multiforme, breast cancer or bladder cancer, which reveals the importance of vitamin K in oncology. Possibly, introduction of vitamin K to the therapy may improve malignancy treatment outcomes. Conclusions: Vitamin K derivatives participate in many metabolic pathways of the human body. Their multifaceted activity may be used both in prevention of many diseases and in their potential treatments. However, further multicentre studies are necessary to understand better possible therapeutic properties of vitamin K derivatives.

Introduction: Severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) are frequently comorbid diseases caused by type 2 inflammation. The complete etiology of these forms still remains unexplained, which makes causal and fully effective therapeutic management impossible. New therapeutic options using the knowledge of Th2 inflammatory endotype are based on anti-IL5 (mepolizumab, reslizumab), anti-IL5R (benralizumab), anti-IgE (omalizumab), and anti-IL4/IL13 (dupilumab) monoclonal antibodies. Recently, biological therapy has provided a new personalized therapeutic option for patients with CRSw NP. Aim: The aim of the study was to evaluate the efficacy of mepolizumab, benralizumab, omalizumab, and dupilumab in the reduction of rhinological symptoms in severe asthmatic patients with chronic rhinosinusitis with nasal polyps. Materials and methods: In 32 (9 male, 18%) patients with CRSwNP and severe bronchial asthma treated with biologics – mepolizumab (19, 59%), omalizumab (5, 15%), benralizumab (6, 19%), and dupilumab (2, 6%) for 6 months, a subjective evaluation of rhinologic symptoms was conducted (TNSS, SNOT, smell evaluation). Results: In all analyzed groups, 6-month treatment with mepolizumab, omalizumab, and benralizumab resulted in significant improvement in rhinitis symptoms assessed by TNSS and SNOT scales as well as in the sense of smell. Due to the small group of patients treated with dupilumab, statistical analysis in this group was not performed. Conclusions: Our real-life observation confirmed that biological therapy based on phenotyping enables achieving optimal therapeutic effects for patients with CRSwNP and severe bronchial asthma. Biological therapy should be conducted through a collaborative and multidisciplinary approach.

Background: Severe asthma is associated with significant morbidity and risk of complications. Some patients, suffering from eosinophilic asthma, may benefit from biological therapies, especially anti IL-5 (anti-interleukin-5). The purpose of the study was to compare the efficacy evaluation of mepolizumab and benralizumab in the treatment of eosinophilic asthma. Methods: A retrospective, single-centre study including 59 patients with severe eosinophilic asthma treated with biologics (mepolizumab and benralizumab). Clinical outcomes, including peripheral blood morphotic characteristics, spirometry parameters, asthma control questionnaire (ACQ), mini-Asthma Quality of Life Questionnaire (mini-AQLQ) scores, daily oral corticosteroid use, body mass index, exacerbation rate, and exercise tolerance, were examined at the beginning and after 6 months of biological treatment. Results: A total of 38 patients were treated with mepolizumab and 21 with benralizumab. Significant improvements (p < 0.05) in eosinophil count, required daily dose of glucocorticoids, ACQ, mini-AQLQ scores, and exacerbation rate were observed in both groups after six months of treatment. There was no statistical difference (p < 0.05) in the abovementioned parameters between the groups. Conclusions: In patients with severe eosinophilic asthma, mepolizumab and benralizumab were associated with significant improvements in clinical state. Patients with type 2 asthma will benefit from the therapy with both anti-IL5 biologic drugs.