Synthesis and characterization of Fe3O4-PEG-LAC-chitosan-PEI nanoparticle as a survivin siRNA delivery system.

The limited effectiveness of the conventional methods for cancer treatment makes the researchers to find novel safe and effective therapeutic strategies. One of these strategies is to use small interfering RNAs (siRNAs). A major challenge here is the siRNA delivery into the cells. The purpose of this study was to design and prepare a biocompatible, biodegradable, and safe nanosized particle for siRNA delivery into human breast cancer MCF-7 and leukemia K562 cells. Chemically synthesized magnetic nanoparticles containing polyethyleneglycol-lactate polymer (PEG-LAC), chitosan, and polyethyleneimine (PEI) were successfully prepared and used as a gene delivery vehicle. The nanoparticles were characterized by Fourier transform infrared spectroscopy and zeta potential. The Fe3O4-PEG-LAC-chitosan-PEI nanoparticle showed efficient and stable survivin siRNA loading in gel retardation assay. The cytotoxicity of the prepared nanoparticle was studied using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and was compared with that of mitoxantrone (MTX) in combination with the prepared siRNA delivery system to evaluate the possible synergic effect of MTX and survivin siRNA. The nanoparticles with and without noncomplementary siRNA showed low toxicity against both cell lines; however, a twofold decrease was observed in cell survival percent after MTX addition to MCF-7 cells treated with either nanoparticle itself or complexed with noncomplementary siRNA. While survivin siRNA nanoplex caused threefold decrease in the cell survival percent, its combination with MTX did not result in a significant increase in the cytotoxic effect. Therefore, Fe3O4-PEG-LAC-chitosan-PEI nanoparticle should be considered as a potential carrier for enhanced survivin siRNA delivery into MCF-7 and K562 cells.

Synthesis and characterization of thermosensitive and pH-sensitive poly (N-isopropylacrylamide-acrylamide-vinylpyrrolidone) for use in controlled release of naltrexone.

In this article N-isopropylacrylamide (NIPAAm)-acrylamide (AAm)-vinyl pyrrolidone (VP) terpolymers were prepared using free radical copolymerization method by varying feed ratios of monomers. The composition ratio and structure of polymer were determined by NMR and FTIR. The glass transition temperature was examined by DSC. The thermo-responsive behaviors of polymeric solutions were investigated by turbidimetry using UV-Visible spectroscopy. The sol-gel transition of the polymer solutions occurred reversibly within 1 min in response to the temperature. By alternating the monomer feed ratio, the synthesized terpolymers had their own distinctive lower critical solution temperature (LCST). In addition to the thermosensitivity, the terpolymers also showed a response to pH changes. The increase in ionic strength of the buffer solution with addition of salt lowered the LCST of the polymers. The ability to shift the phase transition temperature of the terpolymers provided excellent flexibility in tailoring transitions for specific uses. Swelling experiments were performed on the terpolymer disks in buffer solutions with different pH and ionic strength at varying temperature. We investigated naltrexone release as a model drug in phosphate buffer. Drug loading efficiency was varying from 8.75 to 55%. Gel composition, pH, and ionic concentration affected the drug loading. Finally in vitro drug release studies at 36-37 degrees C indicating 35-70% naltrexone release from terpolymers at the end of 30 days. In addition, these gels sustained naltrexone release for 30 days.

[Oncologic mistletoe therapy: physicians' use and estimation of efficiency]. / Onkologische Misteltherapie--zur Anwendung und Bewertung der Wirksamkeit durch Arzte.

BACKGROUND AND OBJECTIVES: In the field of unorthodox therapies in oncology, mistletoe extracts represent the most important method in Germany. In spite of its use for decades, there is no sufficient evidence for its efficiency. Since physicians have been identified to be the main providers of unconventional cancer therapies, the question of what experiences they have made using mistletoe extracts and other methods. PERSONS AND METHODS: In a cross-sectional study, 202 physicians in their private practices answered a structured, pretested questionnaire on unconventional cancer therapies, including their attitudes towards them and their judgement on efficiency. Response rate 80.2%. RESULTS: 79.2% of the physicians reported to provide unconventional cancer therapies, especially older and more experienced doctors. Among these, the rate of physician with a special preference of mistletoe extracts was 44.4%. The average probability to achieve complete or partial remissions with mistletoe extracts, eventually in combination with other unconventional methods was estimated to be 6% and 15%, thus receiving slightly lower estimates than other methods. With respect to changes in quality of life, use of mistletoe extracts was judged to be inferior to other methods (pT-Test = 0.063; pT-Test = 0.059). Furthermore, mistletoe extracts were significantly less frequently used because the physician was convinced of its efficiency (p = 0.025). CONCLUSION: Clinical studies to prove possible benefits of mistletoe extracts are mandatory. It remains unclear why this method has become so popular in spite of providers moderate judgments on efficiency.

The attitudes of physicians and oncologists towards unconventional cancer therapies (UCT).

Physicians represent the main providers of unconventional cancer therapies (UCT) in Germany. However, little is known about providers' characteristics, as well as their attitudes towards UCT. 833 questionnaires on this topic answered by general practitioners and hospital physicians were analysed. Providers differed significantly from non-providers with respect to gender (male>female, i.e. more male providers), age (older>younger), amount of subjective knowledge about UCT, place of work (office>hospital>university clinic), greater wish for coverage of UCT costs, the belief in future positive trends concerning UCT, the recognition of patients' demand for UCT, the number of patients seen per month and medical specialty (GPs>oncologists and radiation oncologists). UCT were not considered to be highly effective, but estimations varied considerably. Further investigations in this area, better education about UCT, training in coping strategies with the fate of cancer patients, and reasonable complementary treatments appear to be of the utmost importance.

Analysis of lipids by one-dimensional thin-layer chromatography.

A high-efficiency silica gel, (type HLF) thin-layer chromatography plate (HETLC), linear high-performance thin-layer chromatography plate (HPTLC) and densitometry method has been devised in order to resolve the major lipid classes obtained from rat brain tissues. This methodology, which has largely overcome prior problems, enhances the opportunity for assessing the glycerophospholipid and glycolipid compositions of tissues. DEAE-Sephadex column chromatography was used to separate the crude lipids extract into neutral and acidic lipid fractions. The lipid fractions were then spotted on separate HPTLC and HETLC plates and chromatographed in one dimension using one solvent system. Quantitation was by in situ densitometry with the absolute quantity of the lipid classes determined from co-chromatographed standards. Sensitivity was increased by using cupric sulfate reagent, which was found to be more sensitive than the conventional cupric acetate reagent. This method is applicable to a broader separation of lipid classes and has improved sensitivity.