247 research outputs found
Improving solubility and chemical stability of natural compounds for medicinal use by incorporatng into liposomes
Designing Virtual River: a Serious Gaming Environment to Collaboratively Explore Management Strategies in River and Floodplain Maintenance
Complete thoracoscopic enucleation of giant leiomyoma of the esophagus: a case report and review of the literature
Photocytotoxicity of mTHPC (Temoporfin) Loaded Polymeric Micelles Mediated by Lipase Catalyzed Degradation
Purpose. To study the in vitro photocytotoxicity and cellular uptake of biodegradable polymeric micelles loaded with the photosensitizer mTHPC, including the effect of lipase-catalyzed micelle degradation. Methods. Micelles of mPEG750-b-oligo(ɛ-caprolactone)5 (mPEG750-b-OCL5) with a hydroxyl (OH), benzoyl (Bz) or naphthoyl (Np) end group were formed and loaded with mTHPC by the film hydration method. The cellular uptake of the loaded micelles, and their photocytotoxicity on human neck squamous carcinoma cells in the absence and presence of lipase were compared with free and liposomal mTHPC (Fospeg ®). Results. Micelles composed of mPEG750-b-OCL5 with benzoyl and naphtoyl end groups had the highest loading capacity up to 30 % (w/w), likely due to π–π interactions between the aromatic end group and the photosensitizer. MTHPC-loaded benzoylated micelles (0.5 mg/mL polymer) did not display photocytotoxicity or any mTHPC-uptake by the cells, in contrast to free and liposomal mTHPC. After dilution of the micelles below the critical aggregation concentration (CAC), or after micelle degradation by lipase, photocytotoxicity and cellular uptake of mTHPC were restored. Conclusion. The high loading capacity of the micelles, the high stability of mTHPC-loaded micelles above the CAC, and the lipase-induced release of the photosensitizer makes these micelles very promising carriers for photodynamic therapy in vivo. KEY WORDS: drug release; enzymatic degradation; meta-tetra(hydroxyphenyl)chlorin (mTHPC); photodynamic therapy (PDT); polymeric micelles
Increased serum sTRAIL levels were correlated with survival in bevacizumab-treated metastatic colon cancer
Self-assembled nanogel made of mannan : synthesis and characterization
Amphiphilic mannan (mannan-C16) was synthesized by the Michael addition of hydrophobic 1-hexadecanethiol (C16)
to hydroxyethyl methacrylated mannan (mannan-HEMA). Mannan-C16 formed nanosized aggregates in water by selfassembly
via the hydrophobic interaction among C16molecules as confirmed by hydrogen nuclearmagnetic resonance (1H
NMR), fluorescence spectroscopy, cryo-field emission scanning electron microscopy (cryo-FESEM), and dynamic light
scattering (DLS). The mannan-C16 critical aggregation concentration (cac), calculated by fluorescence spectroscopy with
Nile red and pyrene, ranged between 0.04 and 0.02mg/mL depending on the polymer degree of substitution ofC16 relative
to methacrylated groups. Cryo-FESEM micrographs revealed that mannan-C16 formed irregular spherical macromolecular
micelles, in this work designated as nanogels, with diameters ranging between 100 and 500 nm. The influence of the
polymer degree of substitution, DSHEMA andDSC16, on the nanogel size and zeta potential was studied byDLS at different
pH values and ionic strength and as a function of mannan-C16 and urea concentrations. Under all tested conditions, the
nanogel was negatively charged with a zeta potential close to zero. Mannan-C16 with higher DSHEMA and DSC16
values
formed larger nanogels andwere also less stable over a 6month storage period and at concentrations close to the cac.When
exposed to solutions of different pH and aggressive conditions of ionic strength and urea concentration, the size of
mannan-C16 varied to some extent but was always in the nanoscale range.International Iberian
Nanotechnology Laboratory (INL)Fundação para a Ciência e a Tecnologia (FCT
Polymeric Micelles in Anticancer Therapy: Targeting, Imaging and Triggered Release
Micelles are colloidal particles with a size around 5–100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use in patients with breast cancer. Micelle-based drug delivery, however, can be improved in different ways. Targeting ligands can be attached to the micelles which specifically recognize and bind to receptors overexpressed in tumor cells, and chelation or incorporation of imaging moieties enables tracking micelles in vivo for biodistribution studies. Moreover, pH-, thermo-, ultrasound-, or light-sensitive block copolymers allow for controlled micelle dissociation and triggered drug release. The combination of these approaches will further improve specificity and efficacy of micelle-based drug delivery and brings the development of a ‘magic bullet’ a major step forward
Susceptibility to chronic mucus hypersecretion, a genome wide association study
Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations.Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and metaanalysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (>= 20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP).Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25610(-6), OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3610 29) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture.Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.</p
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