Acriflavine-loaded solid lipid nanoparticles: preparation, physicochemical characterization, and anti-proliferative properties.

Acriflavine (ACF) is an antiseptic compound with the potential antitumor activity which is used for the fluorescent staining of RNA due to its dominant fluorescent emission at ∼515 nm. Here, solid lipid nanoparticles (SLNs) containing ACF (ACF-SLNs) were prepared and their physicochemical properties, potential geno/cytotoxicity, as well as the fluorescent properties were investigated. FITC-annexin V/PI staining and cell cycle assays were carried out to find the type of cellular death caused. Particle size analysis and SEM images revealed that spherical ACF-SLNs had a homogeneous dispersion with a mean diameter of 106 ± 5.7 nm. Drug loading (DL) of 31.25 ± 4.21 mg/mL and high encapsulation efficiency (EE%) (89.75 ± 5.44) were found. ACF-SLNs physically were relatively stable in terms of dispersion, size, and EE. The uptake study demonstrated the potential use of fluorescent ACF-SLNs in bio-distribution studies. MTT assay showed that plain ACF could induce growth inhibition of A549 cells with IC50 of 8.5, 6, and 4.5 µMol after 24, 48, and 72 hours, respectively, while ACF-SLNs had stable cytotoxic effects after 48 hours. ACF-SLNs induced remarkable apoptosis and even necrosis after 48 h. Conclusively, ACF-SLNs with acceptable physicochemical features showed increased bioimpacts after 48 h compared to plain ACF.

Combining Powder Formulations of Drugs with Food and Beverages to Improve Palatability.

The taste of medicines can significantly affect patient adherence. Pediatric patients often cannot take powder medicines because of their unpleasant taste. Therefore, patients' parents and health care professionals, including pharmacists, often combine medicines with food or beverages to make them easier for pediatric patients to consume because this can reduce their unpleasant taste. The purpose of this study was to evaluate the palatability of powder formulations of azithromycin and carbocysteine and explore their combination with food or beverages to improve palatability for pediatric patients. We quantitatively evaluated the palatability of powder formulations by performing the gustatory sensation test using the visual analog scale score. The gustatory sensation tests were performed on 16 healthy adult volunteers (age 23.0 ± 2.6 years) and indicated that some food and beverages improved the palatability of the powder formulations of azithromycin and carbocysteine. The results of this study indicate that ice cream improves the palatability of azithromycin, while yogurt improves the palatability of carbocysteine. Moreover, the subjects recommended these same combinations for pediatric patients. This study suggests that some foods and beverages improve the palatability of powder formulations, thereby decreasing the possibility that pediatric patients will refuse medications because of their unpleasant taste.

Zinc oxide nanoparticles: Synthesis, antiseptic activity and toxicity mechanism.

Zinc oxide (ZnO), as a material with attractive properties, has attracted great interest worldwide, particularly owing to the implementation of the synthesis of nano-sized particles. High luminescent efficiency, a wide band gap (3.36eV), and a large exciton binding energy (60meV) has triggered intense research on the production of nanoparticles using different synthesis methods and on their future applications. ZnO nanomaterials can be used in industry as nano-optical and nano-electrical devices, in food packaging and in medicine as antimicrobial and antitumor agents. The increasing focus on nano zinc oxide resulted in the invention and development of methods of nanoparticles synthesis. Recently, various approaches including physical, chemical and biological ("green chemistry") have been used to prepare ZnO nanocomposites with different morphologies. The obtained nanoparticles can be characterized with a broad range of analytical methods including dynamic light scattering (DLS), electron microscopy (TEM, SEM), UV-VIS spectroscopy, X-ray diffraction (XRD) or inductively coupled plasma with mass spectrometry (ICP-MS). With these it is possible to obtain information concerning the size, shape and optical properties of nanoparticles. ZnO NPs exhibit attractive antimicrobial properties against bacteria (Gram-positive and Gram-negative) and fungi. Zinc oxide nanocomposites show also selective toxicity toward normal and cancerous cells, which is explained by reactive oxygen formation (ROS). Yet despite the potentially interesting antitumor activity of ZnO nanoparticles, it has been proven that they can be also cytotoxic and genotoxic for multiple types of human cells (i.e. neuronal or epithelial cells). This paper reviews the methods of synthesizing zinc oxide nanocomposites as well as their characteristics, antimicrobial activity and cytotoxicity against normal and tumor cells.

Improved methods for thermal rearrangement of alicyclic α-hydroxyimines to α-aminoketones: synthesis of ketamine analogues as antisepsis candidates.

Ketamine is an analgesic/anesthetic drug, which, in combination with other drugs, has been used as anesthetic for over 40 years. Ketamine induces its analgesic activities by blocking the N-methyl-D-aspartate (NMDA) receptor in the central nervous system (CNS). We have reported that low doses of ketamine administrated to patients before incision significantly reduced post-operative inflammation as reflected by reduced interleukin-6 (IL-6) sera-levels. Our data demonstrated in a rat model of Gram-negative bacterial-sepsis that if we inject a low dose of ketamine following bacterial inoculation we reduce mortality from approximately 75% to 25%. Similar to what we have observed in operated patients, the levels of TNF-α and IL-6 in ketamine-treated rats were significantly lower than in septic animals not treated with ketamine. On the base of these results, we have designed and synthesized series of new analogues of ketamine applying a thermal rearrangement of alicyclic α-hydroxyimines to a-aminoketones in parallel arrays. One of the analogues (compound 6e) displayed high activity in down-regulating the levels of IL-6 and TNF-α in vivo as compared to ketamine.

Acridine: a versatile heterocyclic nucleus.

Acridine is a heterocyclic nucleus. It plays an important role in various medicines. A number of therapeutic agents are based on acridine nucleus such as quinacrine (antimalarial), acriflavine and proflavine (antiseptics), ethacridine (abortifacient), amsacrine and nitracine (anticancer), and tacrine. Acridine is obtained from high boiling fraction of coal tar. It is also obtained in nature from plant and marine sources. Acridine undergoes a number of reactions such as nucleophilic addition, electrophilic substitution, oxidation, reduction, reductive alkylation and photoalkylation. The present review article summarizes the synthesis, reaction, literature review and pharmaceutical importance of acridine.

Local drug delivery system for the treatment of osteomyelitis: In vitro evaluation.

Local antimicrobial delivery is a potential area of research conceptualized to provide alternative and better methods of treatment for cases, as osteomyelitis where avascular zones prevent the delivery of drugs from conventional routes of administration. Drug-loaded polymers and calcium phosphates as hydroxyapatites have been tried earlier. Bioactive glasses are bone-filling materials used for space management in orthopedic and dental surgery. A new bioactive glass (SSS2) was synthesized and fabricated into porous scaffold with a view to provide prolonged local delivery of gatifloxacin and fluconazole as suitable for the treatment of osteomyelitis. The new SSS2 was characterized by Fourier transform infrared (FTIR) and X-ray diffraction (XRD) analyses. In addition, the bioactivity of the SSS2 glass and resulting scaffold was examined by in vitro acellular method and ascertained by FTIR and XRD. The pore size distribution was analysed by mercury intrusion porosimetry and the release of drugs from scaffolds were studied in vitro. The glass and the resulting scaffolds were bioactive indicating that they can bond with bone in vivo. The scaffolds were porous with pores predominantly in the range of 10-60 µm, released the drugs effectively for 6 weeks and deemed suitable for local delivery of drugs to treat osteomyelitis.

Incorporation of low molecular weight biocides into polystyrene-divinyl benzene beads with controlled release characteristics.

Triclosan and phosphonium salt biocides have been separately incorporated into polystyrene-divinylbenzene (PS-DVB) beads by suspension polymerization. Ultraviolet (UV) absorption measurements have been used to monitor the release of these low molecular weight biocides out of the PS-DVB beads immersed in water-ethanol mixtures and in physiological saline. The release of the biocide agents is strongly dependent on either the DVB or/and the antimicrobial composition ratio in the beads. An increase of biocide incorporation in the PS/DVB beads was accompanied by a corresponding enhancement of its concentration in liquid mixtures. On the contrary, higher cross-linking densities hindered the biocide migration out of the beads by diminishing its release rate into either the aqueous ethanol solutions or the natural serum. Moreover, Fourier transform Raman (FT-Raman) spectra and Attenuated Total Reflectance Infrared (ATR-FTIR) measurements of the PS-DVB-Triclosan and PS-DVB-phosphonium salt beads, before and after their immersion in water-ethanol solutions, gave a similar qualitative evidence of the biocide release.