Evaluation of the Antitumor Activity of Quaternary Ammonium Surfactants.

Quaternary ammonium surfactants, due to their diverse chemical structure and their biological properties, can be used in medicine as DNA carriers, disinfectants, and antimicrobial and antitumor agents. In this study, using melanoma A375, colon adenocarcinoma HT-29 and normal human dermal fibroblast (NHDF) cells, we tested the hypothesis that the quaternary ammonium surfactants 2-dodecanoyloxyethyl)trimethylammonium bromide (DMM-11), 2-dodecanoyloxypropyl)trimethylammonium bromide (DMPM-11) and 2-pentadecanoyloxymethyl)trimethylammonium bromide (DMGM-14) act selectively against cancer cells. The results showed that these compounds led to the initiation of the apoptotic process of programmed cell death, as evidenced by the ratio of the relative expression of Bax protein to Bcl-2. The encapsulation of surfactants in liposomes allowed lower concentrations to be used. Moreover, encapsulation reduced their toxicity towards non-cancerous cells. The anticancer efficiency and apoptotic effect of the liposomal formulations with surfactants (DMM-11, DMPM-11 and DMGM-14) were higher than those of surfactant-free liposomes. Therefore, quaternary ammonium surfactant-loaded liposomes show significant potential as delivery vehicles for the treatment of melanoma and colon cancers. The use of nano-formulations offers the advantage of optimizing quaternary ammonium surfactant delivery for improved anticancer therapy.

Recent Advances in the Application of Bacteriophages against Common Foodborne Pathogens.

Bacteriophage potential in combating bacterial pathogens has been recognized nearly since the moment of discovery of these viruses at the beginning of the 20th century. Interest in phage application, which initially focused on medical treatments, rapidly spread throughout different biotechnological and industrial fields. This includes the food safety sector in which the presence of pathogens poses an explicit threat to consumers. This is also the field in which commercialization of phage-based products shows the greatest progress. Application of bacteriophages has gained special attention particularly in recent years, presumably due to the potential of conventional antibacterial strategies being exhausted. In this review, we present recent findings regarding phage application in fighting major foodborne pathogens, including Salmonella spp., Escherichia coli, Yersinia spp., Campylobacter jejuni and Listeria monocytogenes. We also discuss advantages of bacteriophage use and challenges facing phage-based antibacterial strategies, particularly in the context of their widespread application in food safety.

Studies on the Vitrified and Cryomilled Bosentan.

In this paper, several experimental techniques [X-ray diffraction, differential scanning calorimetry (DSC), thermogravimetry, Fourier transform infrared spectroscopy, and broad-band dielectric spectroscopy] have been applied to characterize the structural and thermal properties, H-bonding pattern, and molecular dynamics of amorphous bosentan (BOS) obtained by vitrification and cryomilling of the monohydrate crystalline form of this drug. Samples prepared by these two methods were found to be similar with regard to their internal structure, H-bonding scheme, and structural (α) dynamics in the supercooled liquid state. However, based on the analysis of α-relaxation times (dielectric measurements) predicted for temperatures below the glass-transition temperature (Tg), as well as DSC thermograms, it was concluded that the cryoground sample is more aged (and probably more physically stable) compared to the vitrified one. Interestingly, such differences in physical properties turned out to be reflected in the lower intrinsic dissolution rate of BOS obtained by cryomilling (in the first 15 min of dissolution test) in comparison to the vitrified drug. Furthermore, we showed that cryogrinding of the crystalline BOS monohydrate leads to the formation of a nearly anhydrous amorphous sample. This finding, different from that reported by Megarry et al. [ Carbohydr. Res. 2011, 346, 1061-1064] for trehalose (TRE), was revealed on the basis of infrared and thermal measurements. Finally, two various hypotheses explaining water removal upon cryomilling have been discussed in the manuscript.

pH-Dependent Behavior of Novel Gellan Beads Loaded with Naproxen.

BACKGROUND: Oral administration of non-selective COX inhibitors involves the risk of serious side-effects. In the case of naproxen (NPX), the most frequent are those related to malfunctioning of the gastric mucosa. On the other hand, NPX and other NSAIDs are extensively studied in terms of colorectal cancer (CRC) prevention and inhibition, since it has been evidenced that COX-2 corresponds with the risk of the tumor occurrence and growth. Both side-effects in the stomach and possible antitumor activity of NPX justify the attempts to search for novel carriers for NPX with the site specific release in the colon. Thus, the aim of the work was to design, formulate and characterize low-acyl gellan gum (GG) macro beads as potential carriers for the delivery of NPX to the distal parts of the gastrointestinal tract. METHODS: The beads were obtained by the ionotropic gelation technique. CaCl2 solution was used as a cross-linking medium. After production, the beads were dried and used for further experiments. First, pure NPX and the beads were evaluated by Raman spectroscopy and DSC studies. The surface and morphology of the beads were analyzed by SEM. Next, the drug encapsulation efficiency and content in the beads were determined. The swelling and degradation behavior of the beads were evaluated in four simulated gastrointestinal fluids at different pH (1.2; 4.5; 6.8 and 7.4). The NPX in vitro release studies were conducted on USP I apparatus (rotating basket) at pH=7.4 and compared to the commercial enteric tablet. RESULTS: The polymer content of 0.5 % was considered as too low to obtain spherical beads in the dried form. Raman spectra confirmed that NPX did not undergo structural changes during production process. DSC studies showed that thermal decomposition at lower temperatures was observed for formulations with the lowest amount of GG. It turned out that the most important factor which determined the morphology of the beads was the amount of gellan gum in the initial mixture. The beads revealed 13.9- 39.9% of drug loading and 75.3-99.7% drug encapsulation efficiency. Swelling of the beads was pHdependent as the beads remained stable in the acidic environment but started to absorb water. In pH=7.4 after 3 hours, the beginning of the physical decomposition of the polymer matrix was observed. The drug release studies showed that in pH=7.4 the commercial tablets released 90% of the drug after 45 minutes while the amount of NPX released from pellets after the same time was 40-80%. CONCLUSION: In general, it can be stated that gellan macro beads may be regarded as suitable for site specific delivery of NPX to the colon. However, these simple to obtain beads can be potentially used as carriers for many different drugs whenever it is necessary to omit the stomach.

Polymeric nanoparticles-embedded organogel for roxithromycin delivery to hair follicles.

Drug delivery into hair follicles with the use of nanoparticles (NPs) is gaining more importance as drug-loaded NPs may accumulate in hair follicle openings. The aim was to develop and evaluate a pluronic lecithin organogel (PLO) with roxithromycin (ROX)-loaded NPs for follicular targeting. Polymeric NPs were evaluated in terms of particle shape, size, zeta potential, suspension stability, encapsulation efficiency and in vitro drug release. Lyophilized NPs were incorporated into the PLO and rheological measurements of the nanoparticles-embedded organogels were done. The fate of the NPs in the skin was traced by incorporation of a fluorescent dye into the NPs. As a result, ROX was efficiently incorporated into polymeric NPs characterized by the appropriate size (approximately 300 nm) allowing drug delivery to hair follicles. In ex vivo human skin penetration studies, horizontal skin sections revealed fluorescence deep in the hair follicles. Although the organogel has higher affinity to the lipidic follicular area than an aqueous suspension of NPs, it did not seem to improve penetration of the NPs along the hair shaft. The results proved that it was possible to achieve preferential targeting to the pilosebaceous unit using polymeric NPs formulated either into the aqueous suspension or semisolid topical formulation.

Relationship between surface properties determined by inverse gas chromatography and ibuprofen release from hybrid materials based on fumed silica.

The ability of organic-inorganic hybrid materials to act as drug release-modifying agents was examined. In this study, ibuprofen, a non-steroidal anti-inflammatory drug was used as a model active pharmaceutical ingredient. The physicochemical properties of individual components of the hybrids, as well as these for two- and three-component systems were examined by inverse gas chromatography. The dispersive component of the free surface energy (γ(S)(D)), K(A) and K(D) parameters describing acidity and basicity of hybrid materials, respectively, as well as Flory-Huggins parameters were determined. χ(12)(∞) and [Formula: see text] parameters characterize the interactions between the hybrids and a test solute, or interactions between the drug and inorganic-organic materials, respectively. Additionally, Brunauer-Emmett-Teller (BET) method was used to characterize adsorption activity of the studied materials. The prepared hybrid materials were also characterized by Fourier transform infra-red (FTIR) spectroscopy. The release profiles of ibuprofen for the created hybrid materials were determined. Relationship between the physicochemical activity of hybrid materials and ibuprofen release was presented and discussed.