Study on relation between spatial distribution and release rate of hydrophobic compounds incorporated in polymer micelles with anomalous small angle X-ray scattering

Amphiphilic block copolymers in aqueous solution undergo self-assembly into polymer micelles composed of hydrophobic core and hydrophilic shell. The polymer micelles can solubilize hydrophobic compounds in aqueous solution by incorporating them in the hydrophobic core. Therefore, they have been expected to be a drug career in drug delivery system (DDS). In DDS, controlling of the drug release behavior and retention stability are critical issues. However, tuning release rate and stability of retention of drug molecules is significantly difficult. Since the hydrophobic molecules must pass through the hydrophobic cores and hydrated corona layers to go out the polymer micelles, their release properties should strongly depend on spatial distribution of drug molecules in polymer micelles. Therefore, to elucidate the relation between spatial distribution of drug molecules and release properties of drug molecules is of significant importance to design a novel DDS. Thus, the aim of this study is to clarify the relation between spatial distribution of hydrophobic compounds in polymer micelles and their release and retention property. Poly(methyl methacrylate)-block-poly(N,N-(dimethylamino)ethyl methacrylate) (Poly-1) as amphiphilic block copolymer was synthesized by reversible addition-fragmentation radical polymerization. The weight- and number-average molecular weights of the resulting Poly-1 were 1.6104 g mol-1 and 1.9104 g mol-1, respectively. Three kinds of compounds (9-bromofluorene (BrF), 4-bromobenzyl alcohol (BrBzOH), 4-bromophenol (BrPh)) were employed as bromine-labeled hydrophobic compounds. Poly-1 and a hydrophobic compound were mixed at 10 wt% of a hydrophobic compound against Poly-1. Please click Additional Files below to see the full abstract

Short-term intake of a Japanese-style healthy lunch menu contributes to prevention and/or improvement in metabolic syndrome among middle-aged men: a non-randomized controlled trial

BACKGROUND: Metabolic syndrome is now widely appreciated as a cluster of metabolic abnormalities such as visceral obesity, hypertension, hyperglycemia and dyslipidemia. To date, incidence of metabolic syndrome is continuously increasing worldwide. In addition, low vegetable consumption has recently become a serious issue in Japan. Furthermore, Japan is facing a shortfall in places offering food that can help prevent metabolic syndrome in the first place. Our study is designed to influence these developments. We conducted a non-randomized controlled trial by offering a Japanese-style healthy lunch menu to middle-aged men in a workplace cafeteria. This menu was designed to prevent and reduce metabolic syndrome. METHODS: This intervention study took the form of a non-randomized controlled trial. Participants chose the control or intervention group. The control group consumed their habitual lunches without restriction and only nutrient contents were assessed. The intervention group received a Japanese-style healthy lunch at a workplace cafeteria for 3 months. The participants worked in offices at a city hall and mostly had low levels of physical activity. Data of 35 males (control group: 7 males, intervention group: 28 males, mean age: 47.2 ± 7.9 years) were collected and analyzed. RESULTS: We obtained an effective outcome by demonstrating that ongoing intake of a Japanese-style healthy lunch decreased blood pressure and serum lipids and increased plasma ghrelin levels. The results grew more pronounced as intake of Japanese-style healthy lunches increased in frequency. CONCLUSIONS: This study presents new empirical data as a result of an original intervention program undertaken in Japan. A Japanese-style healthy lunch menu containing many vegetables consumed can help prevent and/or improve metabolic syndrome

Improvement of Cheilitis granulomatosa after Dental Treatment

A 38-year-old male suffered from swelling of the lower lip for 3 months. Neither facial nerve palsy nor fissuring of the tongue was present. Histological examination of a biopsy taken from the lower lip revealed non-caseous epithelioid cell granulomas, suggestive of cheilitis granulomatosa. Patch testing revealed positive reactions to mercury chloride and amalgam. His symptoms markedly improved 3 months after treatment of the apical periodontitis and replacement of dental crowns. As his dental crowns did not contain mercury, we believe that the cheilitis granulomatosa may have been related to the focal dental infection

Reversible conjugation of biomembrane vesicles with magnetic nanoparticles using a self-assembled nanogel interface: single particle analysis using imaging flow cytometry

Nanoscale biomembrane vesicles such as liposomes and extracellular vesicles are promising materials for therapeutic delivery applications. However, modification processes that disrupt the biomembrane affect the performance of these systems. Non-covalent functionalization approaches that are facile and easily reversed by environmental triggers are therefore being widely investigated. In this study, liposomes were successfully hybridized with magnetic iron oxide particles using a cholesterol-modified pullulan nanogel interface. Both the magnetic nanoparticles and the hydrophobic core of the lipid bilayer interacted with the hydrophobic cholesteryl moieties, resulting in stable hybrids after simple mixing. Single particle analysis by imaging flow cytometry showed that the hybrid particles interacted in solution. Calcein loaded liposomes were not disrupted by the hybridization, showing that conjugation did not affect membrane stability. The hybrids could be magnetically separated and showed significantly enhanced uptake by HeLa cells when a magnetic field was applied. Differential scanning calorimetry revealed that the hybridization mechanism involved hydrophobic cholesteryl inserting into the biomembrane. Furthermore, exposure of the hybrids to fetal bovine serum proteins reversed the hybridization in a concentration dependent manner, indicating that the interaction was both reversible and controllable. This is the first example of reversible inorganic material conjugation with a biomembrane that has been confirmed by single particle analysis. Both the magnetic nanogel/liposome hybrids and the imaging flow cytometry analysis method have the potential to significantly contribute to therapeutic delivery and nanomaterial development