Background / Aim: Up until ten years ago stage four melanoma was considered a disease with extremely poor prognosis. Standard therapy during this period of time was dacarbazine chemotherapy. Patients with better performance status were treated with immunotherapy cytokine IL-2. In the last ten years eight medications have been approved by the FDA for the therapy of melanoma. The goal of this study was to determine objective response rate (ORR), median overall survival (OS), median progression free survival (PFS) and safety in patients with advanced and metastatic cutaneous melanoma treated with targeted therapy and immunotherapy at the University Clinical Centre of the Republic of Srpska (Centre). Methods: A non-randomised observational retrospective/prospective trial was conducted to investigate first experiences with the use of targeted therapy and immunotherapy at the Centre and compare the results with the literature data. A total of 23 patients received BRAF targeted therapy for the treatment of metastatic cutaneous melanoma in the first line of treatment. Nine patients received vemurafenib, fourteen patients received a combination of BRAF/MEK inhibitor. Nine patients were treated with pembrolizumab immunotherapy. The trial was performed in a period from May 2017 until December 2020. Results: In patients receiving vemurafenib ORR was 44.4 %, median PFS was 5 months (95 % CI, 1 to 11) and the median OS was 9 months (95 % CI, 2 to 17). In the vemurafenib/cobimetinib group ORR was 71.4 %. Median PFS was 9 months and median OS was 12 months. ORR in patients receiving pembrolizumab was 22.9 %, median PFS was 3 months (95 % CI, 1 to 11) and the median OS was 4.5 months (95 % CI, 2 to 12). Results in all three groups were inferior compared to the results from the literature except for ORR in patients receiving vemurafenib and vemurafenib/cobimetinib. Adverse events were tolerable and manageable and were similar to those described in the literature. Conclusion: Based on the experience with the targeted and immunotherapy in the Centre, which was presented in this study, it was concluded that in conditions when there is limited access to drugs, the greatest benefit have the patients who meet the inclusion criteria in clinical trials.

The aim of the present study is to improve the solubility and antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin by formulating its inclusion complexes with 2-hydroxypropyl-β-cyclodextrin in solution and in solid state. The phase solubility study was used to investigate the interactions between 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and 2-hydroxypropyl-β-cyclodextrin and to estimate the molar ratio between them. The structural characterization of binary systems (prepared by physical mixing, kneading and solvent evaporation methods) was analysed using the FTIR-ATM spectroscopy. The antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and inclusion complexes prepared by solvent evaporation method was tested by the diffusion and dilution methods on various strains of microorganisms. The results of phase solubility studies showed that 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin formed the inclusion complexes with 2-hydroxypropyl-β-cyclodextrin of AP type. The solubility of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin was increased 64.05-fold with 50% w/w of 2-hydroxypropyl-β-cyclodextrin at 37 o C. The inclusion complexes in solid state, prepared by the solvent evaporation method, showed higher solubility in purified water and in phosphate buffer solutions in comparison with 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin alone. The inclusion complexes prepared by solvent evaporation method showed higher activity on Bacillus subtilis and Staphylococcus aureus compared to uncomplexed 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin due to improved aqueous solubility, thus increasing the amount of available 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin that crosses the bacterial membrane.

This review mainly focuses on nanoparticle-based drug delivery systems fabricated from plants (starch, cellulose, pectin), animals (chitosan, gelatin) and microorganisms (dextran). Herein, the focus is on the physical-chemical properties of biopolymers and its derivatives and the mechanism of action in the treatments of cancer. Nanoparticle-based drug delivery systems improved efficacy by: increasing half-life of vulnerable drugs and proteins, improving the solubility of hydrophobic drugs, and allowing controlled and targeted release of drugs in diseased site. Of all the mentioned biopolymers, only dextran and pure pectin are problematic. Some clinical studies have shown unexpected side effects caused by dextran such as thrombocytopenia and hepatotoxicity and, pure pectin-based materials, undesirable swelling and corrosion properties. Doxorubicin has been used in combination with almost all of these biopolymers because it is widely used as an effective chemotherapeutic agent in the treatment of many types of solid tumors of the breast, lung, colon, ovary, prostate and bladder.

Recently, nanotechnology is widely used in agriculture with the aim of achieving high agricultural yields. Due to the unique surface and physicochemical properties, nanomaterials can be used to deliver nutrients to plants via nanoparticles, for the synthesis of nanopesticides, nanofungicides, and to design nanosensors for the detection of very low concentrations of pesticides and other contaminants. Excessive use of pesticides and fertilizers causes the loss of soil biodiversity and the development of resistance to pathogens. Nenoencapsulation of fertilizers, pesticides and herbicides is used for slow and specific dosed release of nutrients as well as agrochemicals. This paper discusses the applications of nanotechnology and their positive effect in agriculture in relation to the common methods used so far.

This paper presents a comprehensive treatment of the complex motion control systems in the the Sliding Mode Control (SMC) framework. The single and multi degrees of freedom (DOF) plants and applications to haptics and functionally related systems are discussed. The paper concentrates on presenting the designs that are easy to apply and tune. The proposed algorithms are based on the application of the equivalent control observer and the convergence term that guaranty stability of the closed loop in a Lyapunov sense and enforces the sliding mode on selected manifolds. Presented SMC design leads to a solution that easily could be modified to include majority of the algorithms presented in the literature.

Development of solid self-nanoemulsifying drug delivery systems (s-SNEDDS) for oral delivery of lysozyme Merima Sirbubalo, Tamás Sovány, Katalin Kristó, Géza Regdon jr, Edina Vranić 1 University of Sarajevo, Faculty of Pharmacy, Department of Pharmaceutical Technology, Sarajevo, Bosnia and Herzegovina 2 University of Szeged, Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, Szeged, Hungary