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Background Efficient localized cervicovaginal antibacterial therapy, enabling the delivery of antibiotic to the site of action at lower doses while escaping systemic drug effects and reducing the risk of developing microbial resistance, is attracting considerable attention. Liposomes have been shown to allow sustained drug release into vaginal mucosa and improve delivery of antibiotics to bacterial cells and biofilms. Azithromycin (AZI), a potent broad-spectrum macrolide antibiotic, has not yet been investigated for localized therapy of cervicovaginal infections, although it is administered orally for the treatment of sexually transmitted diseases. Encapsulation of AZI in liposomes could improve its solubility, antibacterial activity, and allow the prolonged drug release in the cervicovaginal tissue, while avoiding systemic side effects. Purpose The objective of this study was to develop AZI-liposomes and explore their potentials for treating cervicovaginal infections. Methods AZI-liposomes that differed in bilayer elasticity/rigidity and surface charge were prepared and evaluated under simulated cervicovaginal conditions to yield optimized liposomes, which were assessed for antibacterial activity against several planktonic and biofilm-forming Escherichia coli strains and intracellular Chlamydia trachomatis, ex vivo AZI vaginal deposition/penetration, and in vitro cytotoxicity toward cervical cells. Results Negatively charged liposomes with rigid bilayers (CL-3), propylene glycol liposomes (PGL-2) and deformable propylene glycol liposomes (DPGL-2) were efficient against planktonic E. coli ATCC 700928 and K-12. CL-3 was superior for preventing the formation of E. coli ATCC 700928 and K-12 biofilms, with IC 50 values (concentrations that inhibit biofilm viability by 50%) up to 8-fold lower than those of the control (free AZI). DPGL-2 was the most promising for eradication of already formed E. coli biofilms and for treating C. trachomatis infections. All AZI-liposomes were biocompatible with cervical cells and improved localization of the drug inside vaginal tissue compared with the control. Conclusion The performed studies confirm the potentials of AZI-liposomes for localized cervicovaginal therapy.

Nasal route of administration offers a unique opportunity of brain targeted drug delivery via olfactory and trigeminal pathway, providing effective CNS concentrations at lower doses and lower risk for adverse reactions compared to systemic drug administration. Therefore, it has been recently proposed as a route of choice for glucocorticoids to control neuroinflammation processes in patients with severe Covid-19. However, appropriate delivery systems tailored to enhance their efficacy yet need to emerge. In this work we present the development of sprayable brain targeting powder delivery platform of dexamethasone sodium phosphate (DSP). DSP-loaded microspheres, optimised employing Quality-by-Design approach, were blended with soluble inert carriers (mannitol or lactose monohydrate). Powder blends were characterized in terms of homogeneity, flow properties, sprayability, in vitro biocompatibility, permeability and mucoadhesion. Nasal deposition studies were performed using 3D printed nasal cavity model. Mannitol provided better powder blend flow properties compared to lactose. Microspheres blended with mannitol retained or enlarged their mucoadhesive properties and enhanced DSP permeability across epithelial model barrier. DSP dose fraction deposited in the olfactory region reached 17.0% revealing the potential of developed powder platform for targeted olfactory delivery. The observed impact of nasal cavity asymmetry highlighted the importance of individual approach when aiming olfactory region.

Amidži Klari D., Klari I., Veli D., Vedrina Dragojevi I. (2011): Evaluation of mineral and heavy metal contents in Croatian blackberry wines. Czech J. Food Sci., 29: 260-267.The mineral and heavy metal contents in 17 commercially available Croatian blackberry wines were determined by FAAS/FAES and GFAAS. The concentrations of potassium, sodium, calcium, magnesium, iron, copper, manganese, zinc, cobalt, chromium, and cadmium were between (in mg/l) 924-1507, 11.81-120.10, 86.4-457.1, 183.4-381.2, 0.082-6.273, 0.058-0.767, 1.47-11.53, 0.247-6.645, and (in μg/l) 3.21-11.89, 10.08-15.88, and 0.55-9.9, respectively. A negative correlation was found between the concentrations of macro (Mg) and micro (Fe) minerals. Furthermore, positive correlations were observed between the concentrations of manganese, cadmium, and cobalt that indicated the origin of these elements in the anthropogenic source. Multivariate analyses (PCA/LDA) showed that the distinct patterns of the metal contents in blackberry wines could be identified with quite satisfactory accuracy (sensitivity and specificity) with the subregion of the origin. In regard to the results obtained, Croatian blackberry wines could be considered as safe from the health risk point of view and as a good additional source of the essential nutrients investigated such as manganese, magnesium, and potassium.Keywords: blackberry wine; minerals; heavy metal; multivariate analyses; PCA; LDA Blackberry (Rubus fruticosus, Rosaceae) is grown in continental Croatia on small farms using traditional techniques of cultivation and harvesting by hand in summers (July-August). Th ornless Logan, Th ornfree, Black Satin, and Tayberry are the most common blackberry cultivars in Croatia. A signifi cant proportion of fresh fruits is directly processed into blackberry products -jam, juice, or wine. Blackberry wine is a product of yeast fermentation of natural sugars present in blackberry juice. Th is popular fruit wine is mainly produced in the continental part of the country, which is divided into a number of subregions: from the Danube Basin, through Slavonia, Moslavina, Pokuplje, Plešivica, to Prigorje-Bilogora and Zagorje-Međimurje (Figure 1). Slavonia is a geographical and fertile agricultural area in eastern Croatia and the plantations in this subregion are located on the slopes of the central Slavonian mountain range. Prigorje-Bilogora subregion off ers favourable conditions for the cultivation of all kinds of fruits and vegetables, and the plantations are located on attractive hills. Zagorje and Međimurje are situated in the north-western part of the country. Th is subregion features a wide range of diff erent landscapes and types of vegetation.The quality of wine depends on numerous factors related to the specific production area, such as the plant variety, soil and climate, culture, yeast,

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