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Its toxicity was further reduced in the presence of albumin. Taken together, our results indicate that Cho-SMA/AmB micelles could be an intravenous formulation with high antifungal selectivity, and drug interactants-conjugated SMA system could be applied to a variety of drug-loaded nanomicellar systems.This work aims to develop complimentary analytical tools for lipid formulation selection that offer insights into the mechanisms of in-vitro drug release for solid lipid modified release excipients. Such tools are envisioned to aide and expedite the time consuming process of formulation selection and development. Two pharmaceutically relevant solid lipid excipients are investigated, stearyl alcohol and glyceryl behenate, which are generally known to exhibit faster and slower relative release rates, respectively. Nuclear magnetic resonance spectroscopy and diffusometry are used, along with water uptake and dissolution experiments to help distinguish between two proposed in-vitro release mechanisms for crystalline caffeine from these matrices 1) rate limiting movement of the wetting front through the particle, and 2) rate limiting diffusive release of the active from the wetted particle. Findings based on water permeation rates, API diffusion coefficients and kinetic modeling suggest that the rate limiting steps for caffeine release from these matrices are different, with stearyl alcohol being co-rate limited by movement of the wetting front and diffusive release of API, whereas glyceryl behenate is more strictly limited by diffusive release of API from the wetted matrix. A Peclet-like number is proposed to describe the different regimes of rate limitation for drug release. NMR spectroscopy and diffusometry are demonstrated to be useful tools for elucidating mechanisms of API release from crystalline drug/lipid mixtures and have significant potential value as screening tools in MR formulation development.

Numerous microRNAs (miRNAs) have been investigated in the progression of Alzheimer's disease (AD). The purpose of this study was to analyze the expression of miR-433 and its diagnostic value in patients with AD, and to explore the neuroprotective effect of miR-433 in amyloid β (Aβ)-treated SH-SY5Y and SK-N-SH cells.

AD patients and AD cell model that established by Aβ treatment were used in this study. Quantitative real-time PCR was used to measure the expression of miR-433. The diagnostic value of miR-433 was evaluated using the receiver operating characteristic analysis. MTT assay was used to examine the viability of Aβ-treated SH-SY5Y and SK-N-SH cells. Bioinformatics and luciferase activity analyses were used to confirm the target gene that might be involved in the mechanisms of miR-433 in AD.

Expression levels of miR-433 were decreased in AD patients and cells compared with the corresponding controls. The decreased miR-433 expression levels in serum and cerebrospinal fluid (CS) were positively correlated with MMSE scores and had relatively high diagnostic accuracy in AD patients. The gain-of-function experiments found that the overexpression of miR-433 could rescue the Aβ-induced inhibition in neuronal viability in SH-SY5Y and SK-N-SH cells. The luciferase activity results showed that JAK2 was a target gene of miR-433 in neuronal cells.

All the data of this study showed that miR-433 serves as a candidate diagnostic biomarker for AD patients, and may have the potential as a novel therapeutic target by ameliorating Aβ-induced neurotoxicity.

All the data of this study showed that miR-433 serves as a candidate diagnostic biomarker for AD patients, and may have the potential as a novel therapeutic target by ameliorating Aβ-induced neurotoxicity.It is our hypothesis that the presence of an absorptive sink for in-vitro dissolution experiments is decisive to predict extent and duration of super-saturation of low soluble drugs in formulations expected to increase oral absorption, often called enabling formulations. Combined dissolution-/permeation-testing may provide such absorptive sink. Commonly used in-vitro dissolution-/permeation tools have a limited interfacial area-to-donor-volume-ratio (A/V), far below the physiological one which is estimated for humans. find more In consequence, super-saturation is expected to be more pronounced and thus precipitation to occur more readily in these models as compared to the in-vivo situation. In the current study, a PermeaLoop™ prototype a of a novel in-vitro dissolution-/permeation-tool with a substantially larger A/V was employed to investigate the dissolution and permeation behaviour of model formulations of dipyridamole containing fumaric acid as modifier of the micro-environmental pH. After identifying the most suitaLoop prototype are still to be solved, as dispersed drug still tends to get stuck inside the system, but gained experiences are helpful for the improvement of the design.Four formulations of nanostructured lipid carriers (NLC) loaded with curcuminoids where prepared, testing two types of solid lipids (Compritol® 888 ATO and Precirol® ATO 5) and two kinds of stabilizers (poloxamer 407 and polysorbate 80). Particle size values between 111 and 214 nm and polydispersity indices less then 0.3 were registered, with low Z potential values due to the nonionic character of the stabilizers. The results showed that the type of surfactant had an impact on the in vitro release rate and on the ex vivo skin permeation capability of curcuminoids. Polysorbate 80 delayed the release, but favors the transport of a higher amount of curcuminoids to the receptor solution during the ex vivo permeation studies than the systems with poloxamer 407. Confocal microscopy confirmed that all systems favored the penetration of curcuminoids to deeper layers of the skin and in a greater amount than curcuminoids in solution. Exposure of the systems to intense radiation caused the degradation of curcuminoids, without loss of antioxidant activity, confirming that the degradation products also function as antioxidants. The NLC prepared can be valuable carriers to enhance the penetration of curcuminoids into the skin, to treat different disorders and skin diseases.