Biljana Tubić

Biological medicinal products obtained through the application of recombinant DNA technology (biopharmaceuticals) represent a relatively new generation of medicines. They were developed to improve therapeutic efficacy and reduce toxicity associated with synthetic therapies. As biological medicinal products are produced by living organisms and are characterised by high molecular weight and complex three-dimensional structures that cannot be fully defined by simple chemical formulas, they possess specific characteristics that distinguish them from chemically synthesised medicinal products. Biological medicinal products require specific regulatory approaches throughout the marketing authorisation process. Pharmacists and other healthcare professionals involved in the handling of biological medicinal products must pay particular attention to appropriate storage conditions and handling procedures. Furthermore, careful monitoring of adverse reactions is essential, as these reactions are frequently associated with the immunogenic potential of biological medicinal products. Biopharmaceuticals are often high-cost therapeutic options, and their accessibility remains a significant challenge for many healthcare systems. The development and introduction of biosimilar medicinal products represent an important opportunity to improve patient access by providing more cost-effective therapeutic alternatives, although they also introduce specific regulatory challenges due to the complexity of demonstrating biosimilarity.

The pharmacological potential of Lamiaceae plants is primarily linked to their high content of phenolic acids and flavonoids, known for strong antioxidant properties. This study investigated the antioxidant activity of ten widely used Lamiaceae herbs—oregano, lavender, basil, savory, garden thyme, wild thyme, sage, rosemary, lemon balm, and mint—prepared as traditional infusions and microwave-assisted extracts. The antioxidant capacity was evaluated using spectrophotometric assays, and total phenolics and flavonoids were quantified via spectrophotometry and HPLC. Chemometric analysis (PCA) was applied to explore correlations among antioxidant parameters. The results demonstrated excellent antioxidant activity across all samples. The IC50 for DPPH radicals was in the range from 3.73(0.13) to 8.03(0.17) μg/mL and that for ABTS radicals was from 2.89(0.12) to 8.55(0.34). The CUPRAC antioxidant assay delivered values in the range from 351.93(11.85) to 1129.68(44.46) μg TE/mg DE. The FRAP method produced values from 1.27(0.03) to 6.60(0.26) μmol Fe/mg DE. The presence of gallic acid was detected in all examined samples, with lemon balm and lavender exhibiting the highest concentrations across both applied extraction methods. Notably, lavender showed especially high levels of p-hydroxybenzoic acid and chlorogenic acid. Microwave-assisted extraction generally yielded higher levels of bioactive compounds compared to infusion. These findings highlight the potential of Lamiaceae herbal extracts, particularly those obtained through microwave-assisted extraction, as valuable sources of dietary antioxidants for everyday use.

Cytochrome P450 (CYP450) enzymes are pivotal in the metabolism of numerous anticancer agents, with CYP3A4 being the predominant isoform involved. Inhibition of CYP450 enzymes is a major mechanism underlying clinically significant drug-drug interactions (DDIs), particularly in oncology, where polypharmacy is frequent. This review aims to provide a comprehensive and critical overview of CYP450 enzyme inhibition, focusing specifically on the impact of kinase inhibitors (KIs) and poly adenosine diphosphate-ribose polymerase (PARP) inhibitors. A systematic review of the current literature was conducted, focusing on the molecular mechanisms of CYP450 inhibition, including reversible, time-dependent, mechanism-based, and pseudo-irreversible inhibition. Specific attention was given to the inhibitory profiles of clinically relevant KIs and PARP inhibitors, with analysis of pharmacokinetic consequences and regulatory considerations. Many KIs, such as abemaciclib and ibrutinib, demonstrate time-dependent or quasi-irreversible inhibition of CYP3A4, while PARP inhibitors like olaparib and rucaparib exhibit moderate reversible and time-dependent CYP3A4 inhibition. These inhibitory activities can significantly alter the pharmacokinetics of co-administered drugs, leading to increased risk of toxicity or therapeutic failure. Regulatory guidelines now recommend early identification of time-dependent and mechanism-based inhibition using physiologically based pharmacokinetic) (PBPK) modeling. CYP450 inhibition by KIs and PARP inhibitors represents a critical but often underappreciated challenge in oncology pharmacotherapy. Understanding the mechanistic basis of these interactions is essential for optimizing treatment regimens, improving patient safety, and supporting personalized oncology care. Greater clinical vigilance and the integration of predictive modeling tools are necessary to mitigate the risks associated with CYP-mediated DDIs.

Eryngium amethystinum L is a plant which grows in Balkan and Apennine peninsulas. The aerial parts, roots and fruits are used in ethnopharmacology of Italy and Western Balkan countries. Traditional preparations of E amethystinum were used in treatment of oedema, malaria and gastrointestinal diseases. Essential oils and extracts were isolated from aerial parts and roots of E amethystinum and examined by antimicrobial, antioxidative and cytotoxic assays. Gas-chromatography analysis showed predominance of germacrene D and spathulenol in essential oils of E amethystinum aerial parts, which have contributed to strong cytotoxic activity, while the methanolic extract exhibited strong antioxidative and antimicrobial activity. This article summarises all existing knowledge regarding E amethystinum, its chemical composition and pharmacological activity.

Deep eutectic solvents (DESs) are now widely recognized as a new class of ionic liquid analogues and have large-scale usage as green solvents. Due to their superior characteristics compared to traditional organic solvents, DESs are increasingly being used. The aim of the work was to examine the effectiveness of DES extractants of phenolic compounds from monocomponent teas from plants of the Lamiaceae family produced at the Institute for the Study of Medicinal Plants, “Dr. Josif Pančić”. Ten samples of herbal drugs (basil, thyme, savory, oregano, sage, thyme, mint, lavender, rosemary, and lemon balm) were tested. Extraction was performed with two types of DESs (a mixture of menthol and methylsalicylate (1:1) and a mixture of menthol and dodecanoic acid (2:1)), as well as microwave and traditional extraction. The content of phenolic acids and flavonoids in the tested preparations was determined using high-performance liquid chromatography (HPLC). Menthol–methylsalicylate and menthol–dodecanoic acid mixtures showed significant efficiency in the isolation of quercetin and naringenin from herbal drugs, while the effectiveness of the menthol–methylsalicylate mixture stands out in the isolation of chlorogenic acid and cinnamic acid from all samples, as well as rosmarinic acid from basil. The concentration of quercetin ranged from 0.2035 to 0.7543 mg/g of the drug for the menthol–methylsalicylate mixture, and from 0.1189 to 0.2025 mg/g of the drug for the menthol–dodecanoic acid mixture. In this study, an environmentally friendly, economical, and efficient extraction based on menthol and methylsalicylate, and also menthol and dodecanoic acid, was applied. Based on the results presented, DESs may be useful in the isolation of target compounds from plants. This research represents an excellent basis for further research and testing of other green solvents as new extractants.

The use of biological medicines (called “biologics”) has contributed to the progress of the treatment of many chronic diseases, such as cancer, rheumatoid arthritis, Crohn’s disease, multiple sclerosis, and psoriasis. However, biologics are expensive for healthcare systems in many countries, and their availability has been an issue for many patients worldwide. A biosimilar medicine (called “biosimilar“) is a medicine with a proven similarity in terms of quality, biological activity, safety, and efficacy as the approved original biological medicine (called “originator biologic“).Biosimilars generate competition in the market by lowering the prices of biologics, thereby increasing access for patients. However, there are barriers to the acceptance and use of biosimilars in respect of their safety and interchangeability with the originator biologic. In this review, we present the national regulatory framework for biologics along with its limitations, the system for monitoring the safety profile of biologics, the interchangeability guideline, and a list of approved and available biologics in Bosnia and Herzegovina. Recommendations were also made here in order to create opportunities for better acceptance of biosimilars and thus better access to biologics. These recommendations include, but are not limited to, strengthening the national regulatory framework for biologics, capacity building, increasing awareness among healthcare providers for reporting adverse drug events and active pharmacovigilance, and better definitions of interchangeability. Finally, awareness of biosimilars and biologics among healthcare providers should be raised through continuous education and workshops, and by including this important topic in graduate and post-graduate curricula in the country.