Investigating the prilling/vibration technique to produce gastric-directed drug delivery systems for misoprostol.

Prilling/vibration technique to produce oral microcapsules was explored to achieve local delivery of misoprostol (MIS), a prostaglandin E1 analogue indicated for the treatment of gastric-duodenal ulcers, at the gastric mucosa. To improve MIS chemical stability and reduce its associated systemic side effects, drug delivery systems were designed and developed as microcapsules consisting of a core of sunflower oil and MIS (Fs6 and Fs14) or a MIS complex with hydroxypropyl-beta-cyclodextrin (HP-ß-CD) (Fs18), confirmed by specific studies, and a polymeric shell. The produced microcapsules showed high encapsulation efficiencies for those with MIS solubilized in sunflower oil (>59.86 %) and for the microcapsules with MIS/HP-ß-CD (97.61 %). To demonstrate the ability of these systems to deliver MIS into the stomach, swelling and drug release experiments were also conducted in simulated gastric fluid. Among the three formulations, FS18 showed gastric release within 30 min and was the most advantageous formulation because the presence of the MIS/HP-ß-CD inclusion complex ensured a greater ability to stabilise MIS in the simulated gastric environment. In addition, these new systems have a small size (<540 µm), and good flow properties and the dose of the drug could be easily adapted using different amounts of microcapsules (flexibility), making them a passepartout for different age population groups.

Magnetic implants in vivo guiding sorafenib liver delivery by superparamagnetic solid lipid nanoparticles.

HYPOTHESIS: Solid lipid nanoparticles (SLNs), co-encapsulating superparamagnetic iron oxide nanoparticles and sorafenib, have been exploited for magnetic-guided drug delivery to the liver. Two different magnetic configurations, both comprising two small magnets, were under-skin implanted to investigate the effect of the magnetic field topology on the magnetic SLNP accumulation in liver tissues. A preliminary simulation analysis was performed to predict the magnetic field topography for each tested configuration. EXPERIMENTS: SLNs were prepared using a hot homogenization approach and characterized using complementary techniques. Their in vitro biological behavior was assessed in HepG-2 liver cancer cells; wild-type mice were used for the in vivo study. The magnet configuration that resulted in a higher magnetic targeting efficiency was investigated by evaluating the iron content in homogenated murine liver tissues. FINDINGS: SLNs, characterized by an average size smaller than 200 nm, retained their superparamagnetic behavior and relevant molecular resonance imaging properties as negative contrast agents. The evaluation of iron accumulation in the liver tissues was consistent with the magnetic induction profile of each magnet configuration, concurring with the results predicted by simulation analysis and obtained by measurements in living mice.

Stability of Diazepam Enema Extemporaneous Formulation in Manzoni Base.

The authors provide a report on the preparation of an extemporaneous liquid formulation of diazepam enema using an alcohol-free base solution for use by both pediatric and adult patients. A solubility study using this base and the chemical stability of the drug in this formulation was performed by using a high-pressure liquid chromatography analytical method. Results of this study showed that the intrinsic solubility of the drug in this liquid base was 6.03 mg/mL ± 0.06 mg/mL and that diazepam was chemically stable when the formulation was stored at 25°C over a period of 3 months.

Grape seed extracts modify the outcome of oxaliplatin in colon cancer cells by interfering with cellular mechanisms of drug cytotoxicity.

Grape seed extracts are commonly utilized as dietary supplements for their antioxidant properties, even from cancer patients. However, whether these natural extracts interfere with chemotherapeutics utilized in colon cancer treatment is still poorly investigated. The cytotoxicity of extracts from Italia and Palieri cultivars either alone or in combination with oxaliplatin was evaluated in colon cancer cells. Grape seed extracts displayed anti-proliferative activity depending on the concentration utilized through apoptosis induction. In combination, they affected the activation of Erk1/2 and counteracted the intrinsic and the extrinsic pathway of apoptosis, the DNA damage and the generation of ROS induced by oxaliplatin. Noteworthy grape seed extracts strongly enhanced the uptake of oxaliplatin into all cells, by affecting the cell transport system of platinum. The addition of these natural extracts to oxaliplatin strongly reduced the cellular response to oxaliplatin and allowed a huge accumulation of platinum into cells. Here, we shed light on the chemical biology underlying the combination of grape seed extracts and oxaliplatin, demonstrating that they might be detrimental to oxaliplatin effectiveness in colon cancer therapy.

Structure-activity relationships and effects on neuroactive steroid synthesis in a series of 2-phenylimidazo[1,2-a]pyridineacetamide peripheral benzodiazepine receptors ligands.

A series of 36 imidazopyridineacetamides (2-37) were designed and synthesized to evaluate the effects of structural changes on the amide nitrogen at both central (CBRs) and peripheral benzodiazepine receptors (PBRs). These changes include variations in the length and number of the alkyl groups as well as introduction of different aromatic, heteroaromatic, and conformationally constrained groups. The affinities of these compounds for CBRs and PBRs were determined, and the results indicate that bulkiness of the substituents, their branching, and length beyond an optimal value may cause hindrance to the ligand in its interaction with the receptor. The presence of aromatic or conformationally constrained substituents on the carboxamide nitrogen can be conducive to high affinity and selectivity. Furthermore, the ability of a subset of the most active ligands to stimulate synthesis of neuroactive steroids in plasma and brain was evaluated in vivo and in vitro. Compound 3 exhibited very marked effects on the peripheral and central synthesis of neuroactive steroids, while 36 (potent at subnanomolar level) showed a slight ability to affect neuroactive steroid content in the cerebral cortex.