Two-Dimensional (2D) Hybrid Method: Expanding 2D Correlation Spectroscopy (2D-COS) for Time Series Analysis.

We present a concise report on the two-dimensional (2D) hybrid method, an innovative extension of 2D correlation spectroscopy, tailored for quasar light curve analysis. Addressing the challenge of discerning periodic variations against the background of intrinsic "red" noise fluctuations, this method employs cross-correlation of wavelet transform matrices to reveal distinct correlation patterns between underlying oscillations, offering new insights into quasar dynamics.

Precision Medicines for Retinal Lipid Metabolism-Related Pathologies.

Oxidation of lipids and lipoproteins contributes to inflammation processes that promote the development of eye diseases. This is a consequence of metabolism dysregulation; for instance, that of the dysfunctional peroxisomal lipid metabolism. Dysfunction of lipid peroxidation is a critical factor in oxidative stress that causes ROS-induced cell damage. Targeting the lipid metabolism to treat ocular diseases is an interesting and effective approach that is now being considered. Indeed, among ocular structures, retina is a fundamental tissue that shows high metabolism. Lipids and glucose are fuel substrates for photoreceptor mitochondria; therefore, retina is rich in lipids, especially phospholipids and cholesterol. The imbalance in cholesterol homeostasis and lipid accumulation in the human Bruch's membrane are processes related to ocular diseases, such as AMD. In fact, preclinical tests are being performed in mice models with AMD, making this area a promising field. Nanotechnology, on the other hand, offers the opportunity to develop site-specific drug delivery systems to ocular tissues for the treatment of eye diseases. Specially, biodegradable nanoparticles constitute an interesting approach to treating metabolic eye-related pathologies. Among several drug delivery systems, lipid nanoparticles show attractive properties, e.g., no toxicological risk, easy scale-up and increased bioavailability of the loaded active compounds. This review analyses the mechanisms involved in ocular dyslipidemia, as well as their ocular manifestations. Moreover, active compounds as well as drug delivery systems which aim to target retinal lipid metabolism-related diseases are thoroughly discussed.

Effect of Hydrophilic Polymers on the Release Rate and Pharmacokinetics of Acyclovir Tablets Obtained by Wet Granulation: In Vitro and In Vivo Assays.

This study aims to evaluate the feasibility of producing acyclovir-containing modified release matrix tablets by a wet granulation method based on the type and concentration of two pharmaceutical-grade hydrophilic matrix polymers (i.e., hydroxypropyl methylcellulose (HPMC), carbomers, and their combinations) commonly used in biomedical applications. The mechanical properties of the tablets and in vitro and in vivo performance were studied. The physicochemical properties of the raw materials and corresponding physical mixtures were characterized by differential scanning calorimetry, showing that the hydrophilic polymers did not influence the physicochemical properties of the drug. The wet granulation process improved the flow and compression properties of the obtained granules. This method enabled the preparation of the matrix tablets of acyclovir with appropriate mechanical properties concerning hardness and friability. The drug release kinetics was governed by the type and concentration of the hydrophilic polymers composing the matrices. The study has proven that HPMC-composed tablets were superior in modified drug release properties compared to carbomer- and HPMC/carbomer-based tablets. Mathematical analysis of the release profiles, determined in a medium adjusted to pH 1.2 followed by pH 7.4, revealed that the drug released from the hydrophilic tablets followed non-Fickian first-order kinetics. An optimal HPMC-based formulation submitted to accelerated stability studies (40 °C, 75% RH) was stable for three months. A complete cross-over bioavailability study of the selected acyclovir-loaded sustained release tablets and marketed immediate-release tablets were compared in six healthy male volunteers. The extent of drug absorption from the sustained release tablets was significantly greater than that from immediate-release pills, which may improve the drug's antiviral properties attributed to the lower elimination rate and enhanced acyclovir half-life.

The Habitability of the Galactic Bulge.

We present a new investigation of the habitability of the Milky Way bulge, that expands previous studies on the Galactic Habitable Zone. We discuss existing knowledge on the abundance of planets in the bulge, metallicity and the possible frequency of rocky planets, orbital stability and encounters, and the possibility of planets around the central supermassive black hole. We focus on two aspects that can present substantial differences with respect to the environment in the disk: (i) the ionizing radiation environment, due to the presence of the central black hole and to the highest rate of supernovae explosions and (ii) the efficiency of putative lithopanspermia mechanism for the diffusion of life between stellar systems. We use analytical models of the star density in the bulge to provide estimates of the rate of catastrophic events and of the diffusion timescales for life over interstellar distances.

Preclinical safety of solid lipid nanoparticles and nanostructured lipid carriers: Current evidence from in vitro and in vivo evaluation.

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were designed as exceptionally safe colloidal carriers for the delivery of poorly soluble drugs. SLN/NLC have the particularity of being composed of excipientsalready approved for use in medicines for human use, which offers a great advantage over any other nanoparticulate system developed from novel materials. Despite this fact, any use of excipients in new route of administration or in new dosage form requires evidence of safety. After 25 years of research on SLN and NLC, enough evidence on their preclinical safety has been published. In the present work, published data on in vitro and in vivo compatibility of SLN/NLC have been surveyed, in order to provide evidence of high biocompatibility distinguished by intended administration route. We also identified critical factors and possible weak points in SLN/NLC formulations, such as the effect of surfactants on the cell viability in vitro, which should be considered for further development.

Formulation of solid lipid nanoparticles (SLN): the value of different alkyl polyglucoside surfactants.

Alkyl polyglycosides (APGs) represent a group of nonionic tensides with excellent skin compatibility. Thus they seem to be excellent stabilizers for lipid nanoparticles for dermal application. To investigate this, different APGs were selected to evaluate their influence on the formation and characteristics of solid lipid nanoparticles (SLN). Contact angle analysis of the aqueous solutions/dispersions of the APGs on cetyl palmitate films revealed good wettability for all APG surfactants. Cetyl palmitate based SLN were prepared by hot high pressure homogenization and subjected to particle size, charge and inner structure analysis. 1% of each APG was sufficient to obtain SLN with a mean size between 150 nm and 175 nm and a narrow size distribution. The zeta potential in water was ∼ -50 mV; the values in the original medium were distinctly lower, but still sufficient high to provide good physical stability. Physical stability at different temperatures (5°C, 25°C and 40°C) was confirmed by a constant particle size over an observation period of 90 days in all dispersions. In comparison to SLN stabilized with classical surfactants, e.g., Polysorbate, APG stabilized SLN possess a smaller size, improved physical stability and contain less surfactant. Therefore, the use of APGs for the stabilization of lipid nanoparticles is superior in comparison to classical stabilizers. Further, the results indicate that the length of the alkyl chain of the APG influences the diminution efficacy, the final particle size and the crystallinity of the particles. APGs with short alkyl chain led to a faster reduction in size during high pressure homogenization, to a smaller particle size of the SLN and to a lower recrystallization index, i.e., to a lower crystallinity of the SLN. The crystallinity of the SLN increased with an increase in the alkyl chain length of APGs. Therefore, by using the tested APGs differing in the alkyl chain length, not only small sized and physically stable but also SLN with different sizes and crystallinity can be obtained. An optimized selection of these stabilizers might therefore enable the production of lipid nanoparticles with "tailor-made" properties.