Urejeni mezoporozni silikati kot ogrodja za nadzorovano sproščanje učinkovin

Interest in and thereby also in development of ordered mesoporous silicates as drug delivery devices have grown immensely over the past few years. On hand selected cases from the literature, the power of such systems as delivery devices has been established. Specifically, it is shown how it is possible to enhance the release kinetics of poorly soluble drugs by embedding them in mesoporous silicates. Further critical factors governing the structure and release of the model drug itraconazole incorporated in an SBA-15 matrix are briefly reviewed. The possibility of functionalizing the surface of mesoporous matrices also under harsher conditions offers a broad platform for the design of stimuli-responsive drug release, including pH responsive systems and systems which respond to the presence of specific ions, reducing agents, magnetic field or UV light, whose efficiency and biocompatibility has been established in vitro.V zadnjih letih se je zanimanje za razvoj mezoporoznih silikatov kot dostavnih sistemov zdravilnih učinkovin izredno povečalo. V članku so predstavljeni izbrani primeri iz literature, na osnovi katerih je pokazano, kako lahko z vgrajevanjem v vodi težko topnih zdravilnih učinkovin v mezoporozna silikatna ogrodja dosežemo pospešeno sproščanje tovrstnih zdravilnih učinkovin. Na primeru modelne zdravilne učinkovine itrakonazola so na kratko pojasnjeni kritični dejavniki, ki regulirajo njegovo strukturo in sproščanje iz silikatnega ogrodja SBA-15. Možnost funkcionalizacije površine tudi pri bolj ostrih pogojih nudi bogato paleto na specifične stimuluse občutljivega sproščanja zdravilnih učinkovin. Na ta način lahko razvijemo inteligentne dostavne sisteme, iz katerih se zdravilna učinkovina selektivno sprošča ob določenem stimulusu, kot je sprememba pH medija, prisotnost specifičnih ionov, reducentov, magnetnega polja ali UV svetlobe. Dokazana je tudi njihova biokompatibilnost in učinkovitost v in vitro poskusih

Interplay between tau and \u3b1-synuclein liquid-liquid phase separation

In Parkinson's disease with dementia, up to 50% of patients develop a high number of tau\u2010containing neurofibrillary tangles. Tau\u2010based pathologies may thus act synergistically with the \u3b1\u2010synuclein pathology to confer a worse prognosis. A better understanding of the relationship between the two distinct pathologies is therefore required. Liquid\u2013liquid phase separation (LLPS) of proteins has recently been shown to be important for protein aggregation involved in amyotrophic lateral sclerosis, whereas tau phase separation has been linked to Alzheimer's disease. We therefore investigated the interaction of \u3b1\u2010synuclein with tau and its consequences on tau LLPS. We find \u3b1\u2010synuclein to have a low propensity for both, self\u2010coacervation and RNA\u2010mediated LLPS at pH 7.4. However, full\u2010length but not carboxy\u2010terminally truncated \u3b1\u2010synuclein efficiently partitions into tau/RNA droplets. We further demonstrate that Cdk2\u2010phosphorylation promotes the concentration of tau into RNA\u2010induced droplets, but at the same time decreases the amount of \u3b1\u2010synuclein inside the droplets. NMR spectroscopy reveals that the interaction of the carboxy\u2010terminal domain of \u3b1\u2010synuclein with the proline\u2010rich region P2 of tau is required for the recruitment of \u3b1\u2010synuclein into tau droplets. The combined data suggest that the concentration of \u3b1\u2010synuclein into tau\u2010associated condensates can contribute to synergistic aSyn/tau pathologies

Indomethacin Embedded into MIL-101 Frameworks: A Solid-State NMR Study

Interactions of drug molecules embedded within the pores of drug-delivery matrices significantly influence the drug-release rate and profile. In this Article, we used solid-state NMR experiments to inspect the interactions of indomethacin drug and tetrahydrofuran solvent molecules within mesoporous MIL-101 metal–organic framework materials. MIL-101 matrices were prepared using two types of linkers, terephthalic acid for MIL-101­(Cr) and MIL-101­(Fe), and amino-terephthalic acid for MIL-101­(Al)-NH₂ and MIL-101­(Fe)-NH₂. Loading MIL-101 matrices with indomethacin proved to be very efficient; the obtained delivery systems accommodated from 0.9 to 1.1 g of indomethacin per 1 g of MIL-101 material. NMR measurements showed that regardless of the type of the framework metal centers or the type of the organic linker indomethacin did not attach to the metal–organic framework. Interactions between indomethacin molecules themselves were also not detected. On the contrary, the smaller tetrahydrofuran solvent molecules did attach to the framework metallic trimeric units with hydrogen bonds. The bonds and the geometry of the porous system prevented the tetrahydrofuran molecules to be expelled from the MIL-101 matrix during drying. Information on interactions and proximities among neighboring nuclei was obtained by ¹H homonuclear correlation and ¹H–¹³C heteronuclear correlation NMR measurements. Distance-dependent influence of paramagnetic chromium and iron centers was also exploited