Lipid Vesicles Loaded with an HIV-1 Fusion Inhibitor Peptide as a Potential Microbicide

The effective use of fusion inhibitor peptides against cervical and colorectal infections requires the development of sustained release formulations. In this work we comparatively study two different formulations based on polymeric nanoparticles and lipid vesicles to propose a suitable delivery nanosystem for releasing an HIV-1 fusion inhibitor peptide in vaginal mucosa. Polymeric nanoparticles of poly-d,l-lactic-co-glycolic acid (PLGA) and lipid large unilamellar vesicles loaded with the inhibitor peptide were prepared. Both formulations showed average sizes and polydispersity index values corresponding to monodisperse systems appropriate for vaginal permeation. High entrapment efficiency of the inhibitor peptide was achieved in lipid vesicles, which was probably due to the peptide's hydrophobic nature. In addition, both nanocarriers remained stable after two weeks stored at 4 °C. While PLGA nanoparticles (NPs) did not show any delay in peptide release, lipid vesicles demonstrated favorably prolonged release of the peptide. Lipid vesicles were shown to improve the retention of the peptide on ex vivo vaginal tissue in a concentration sufficient to exert its pharmacological effect. Thus, the small size of lipid vesicles, their lipid-based composition as well as their ability to enhance peptide penetration on vaginal tissue led us to consider this formulation as a better nanosystem than polymeric nanoparticles for the sustained delivery of the HIV-1 fusion inhibitor peptide in vaginal tissues

In situ fast ellipsometric analysis of repetitive surface phenomena

We present an ellipsometric technique and ellipsometric analysis of repetitive phenomena, based on the experimental arrangement of conventional phase modulated ellipsometers ͑PME͒ conceived to study fast surface phenomena in repetitive processes such as periodic and triggered experiments. Phase modulated ellipsometry is a highly sensitive surface characterization technique that is widely used in the real-time study of several processes such as thin film deposition and etching. However, fast transient phenomena cannot be analyzed with this technique because precision requirements limit the data acquisition rate to about 25 Hz. The presented new ellipsometric method allows the study of fast transient phenomena in repetitive processes with a time resolution that is mainly limited by the data acquisition system. As an example, we apply this new method to the study of surface changes during plasma enhanced chemical vapor deposition of amorphous silicon in a modulated radio frequency discharge of SiH 4 . This study has revealed the evolution of the optical parameters of the film on the millisecond scale during the plasma on and off periods. The presented ellipsometric method extends the capabilities of PME arrangements and permits the analysis of fast surface phenomena that conventional PME cannot achieve

Global retrieval of ATSR cloud parameters and evaluation (GRAPE): dataset assessment

The Along-Track Scanning Radiometers (ATSRs) provide a long time-series of measurements suitable for the retrieval of cloud properties. This work evaluates the freely-available Global Retrieval of ATSR Cloud Parameters and Evaluation (GRAPE) dataset (version 3) created from the ATSR-2 (1995�2003) and Advanced ATSR (AATSR; 2002 onwards) records. Users are recommended to consider only retrievals flagged as high-quality, where there is a good consistency between the measurements and the retrieved state (corresponding to about 60% of converged retrievals over sea, and more than 80% over land). Cloud properties are found to be generally free of any significant spurious trends relating to satellite zenith angle. Estimates of the random error on retrieved cloud properties are suggested to be generally appropriate for optically-thick clouds, and up to a factor of two too small for optically-thin cases. The correspondence between ATSR-2 and AATSR cloud properties is high, but a relative calibration difference between the sensors of order 5�10% at 660 nm and 870 nm limits the potential of the current version of the dataset for trend analysis. As ATSR-2 is thought to have the better absolute calibration, the discussion focusses on this portion of the record. Cloud-top heights from GRAPE compare well to ground-based data at four sites, particularly for shallow clouds. Clouds forming in boundary-layer inversions are typically around 1 km too high in GRAPE due to poorly-resolved inversions in the modelled temperature profiles used. Global cloud fields are compared to satellite products derived from the Moderate Resolution Imaging Spectroradiometer (MODIS), Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) measurements, and a climatology of liquid water content derived from satellite microwave radiometers. In all cases the main reasons for differences are linked to differing sensitivity to, and treatment of, multi-layer cloud systems. The correlation coefficient between GRAPE and the two MODIS products considered is generally high (greater than 0.7 for most cloud properties), except for liquid and ice cloud effective radius, which also show biases between the datasets. For liquid clouds, part of the difference is linked to choice of wavelengths used in the retrieval. Total cloud cover is slightly lower in GRAPE (0.64) than the CALIOP dataset (0.66). GRAPE underestimates liquid cloud water path relative to microwave radiometers by up to 100 g m�2 near the Equator and overestimates by around 50 g m�2 in the storm tracks. Finally, potential future improvements to the algorithm are outlined

Gel-Dispersed Nanostructures Lipid Carriers Loading Thymol Designed for Dermal Pathologies

Purpose: Acne vulgaris is one of the most prevalent dermal disorders affecting skin health and appearance. To date, there is no effective cure for this pathology, and the majority of marketed formulations eliminate both healthy and pathological microbiota. Therefore, hereby we propose the encapsulation of an antimicrobial natural compound (thymol) loaded into lipid nanostructured systems to be topically used against acne.Methods: To address this issue, nanostructured lipid carriers (NLC) capable of encapsulating thymol, a natural compound used for the treatment of acne vulgaris, were developed either using ultrasonication probe or high-pressure homogenization and optimized using 22-star factorial design by analyzing the effect of NLC composition on their physicochemical parameters. These NLC were optimized using a design of experiments approach and were characterized using different physicochemical techniques. Moreover, short-term stability and cell viability using HaCat cells were assessed. Antimicrobial efficacy of the developed NLC was assessed in vitro and ex vivo.Results: NLC encapsulating thymol were developed and optimized and demonstrated a prolonged thymol release. The formulation was dispersed in gels and a screening of several gels was carried out by studying their rheological properties and their skin retention abilities. From them, carbomer demonstrated the capacity to be highly retained in skin tissues, specifically in the epidermis and dermis layers. Moreover, antimicrobial assays against healthy and pathological skin pathogens demonstrated the therapeutic efficacy of thymol-loaded NLC gelling systems since NLC are more efficient in slowly reducing C. acnes viability, but they possess lower antimicrobial activity against S. epidermidis, compared to free thymol.Conclusion: Thymol was successfully loaded into NLC and dispersed in gelling systems, demonstrating that it is a suitable candidate for topical administration against acne vulgaris by eradicating pathogenic bacteria while preserving the healthy skin microbiome.</p

Fast optical source for quantum key distribution based on semiconductor optical amplifiers

A novel integrated optical source capable of emitting faint pulses with different polarization states and with different intensity levels at 100 MHz has been developed. The source relies on a single laser diode followed by four semiconductor optical amplifiers and thin film polarizers, connected through a fiber network. The use of a single laser ensures high level of indistinguishability in time and spectrum of the pulses for the four different polarizations and three different levels of intensity. The applicability of the source is demonstrated in the lab through a free space quantum key distribution experiment which makes use of the decoy state BB84 protocol. We achieved a lower bound secure key rate of the order of 3.64 Mbps and a quantum bit error ratio as low as $1.14\times 10^{-2}$ while the lower bound secure key rate became 187 bps for an equivalent attenuation of 35 dB. To our knowledge, this is the fastest polarization encoded QKD system which has been reported so far. The performance, reduced size, low power consumption and the fact that the components used can be space qualified make the source particularly suitable for secure satellite communication

Memantine loaded PLGA PEGylated nanoparticles for Alzheimer's disease: in vitro and in vivo characterization

Background: Memantine, drug approved for moderate to severe Alzheimer's disease, has not shown to be fully efective. In order to solve this issue, polylactic-co-glycolic (PLGA) nanoparticles could be a suitable solution to increase drug's action on the target site as well as decrease adverse efects. For these reason, Memantine was loaded in biodegradable PLGA nanoparticles, produced by double emulsion method and surface-coated with polyethylene glycol. MEM-PEG-PLGA nanoparticles (NPs) were aimed to target the blood-brain barrier (BBB) upon oral administra‑ tion for the treatment of Alzheimer's disease. Results: The production parameters were optimized by design of experiments. MEM-PEG-PLGA NPs showed a mean particle size below 200 nm (152.6±0.5 nm), monomodal size distribution (polydispersity index, PI<0.1) and negative surface charge (−22.4 mV). Physicochemical characterization of NPs confrmed that the crystalline drug was dispersed inside the PLGA matrix. MEM-PEG-PLGA NPs were found to be non-cytotoxic on brain cell lines (bEnd.3 and astrocytes). Memantine followed a slower release profle from the NPs against the free drug solution, allowing to reduce drug administration frequency in vivo. Nanoparticles were able to cross BBB both in vitro and in vivo. Behavio‑ ral tests carried out on transgenic APPswe/PS1dE9 mice demonstrated to enhance the beneft of decreasing memory impairment when using MEM-PEG-PLGA NPs in comparison to the free drug solution. Histological studies confrmed that MEM-PEG-PLGA NPs reduced β-amyloid plaques and the associated infammation characteristic of Alzheimer's disease. Conclusions: Memantine NPs were suitable for Alzheimer's disease and more efective than the free drug

Memantine loaded PEGylated biodegradable nanoparticles for the treatment of glaucoma

Glaucoma is a multifactorial neurodegenerative disease associated with retinal ganglion cells (RGC) loss. Increasing reports of similarities in glaucoma and other neurodegenerative conditions have led to speculation that therapies for brain neurodegenerative disorders may also have potential as glaucoma therapies. Memantine is an N-methyl-d-aspartate (NMDA) antagonist approved for Alzheimer's disease treatment. Glutamate-induced excitotoxicity is implicated in glaucoma and NMDA receptor antagonism is advocated as a potential strategy for RGC preservation. This study describes the development of a topical formulation of memantine-loaded PLGA-PEG nanoparticles (MEM-NP) and investigates the efficacy of this formulation using a well-established glaucoma model. MEM-NPs <200 nm in diameter and incorporating 4 mg mL−1 of memantine were prepared with 0.35 mg mL−1 localized to the aqueous interior. In vitro assessment indicated sustained release from MEM-NPs and ex vivo ocular permeation studies demonstrated enhanced delivery. MEM-NPs were additionally found to be well tolerated in vitro (human retinoblastoma cells) and in vivo (Draize test). Finally, when applied topically in a rodent model of ocular hypertension for three weeks, MEM-NP eye drops were found to significantly (p < 0.0001) reduce RGC loss. These results suggest that topical MEM-NP is safe, well tolerated, and, most promisingly, neuroprotective in an experimental glaucoma model

Detection of ship tracks in ATSR2 satellite imagery

Ships modify cloud microphysics by adding cloud condensation nuclei (CCN) to a developing or existing cloud. These create lines of larger reflectance in cloud fields that are observed in satellite imagery. Ship tracks are most frequently seen off the west coast of California, and the Atlantic coast of both west Africa and south-western Europe. In order to automate their detection within the Along Track Scanning Radiometer 2 (ATSR2) data set an algorithm was developed and integrated with the Global Retrieval of ATSR Cloud Parameters and Evaluation (GRAPE) processing chain. The algorithm firstly identifies intensity ridgelets in clouds which have the potential to be part of a ship track. This identification is done by comparing each pixel with its surrounding ones. If the intensity of three adjacent pixels is greater than the intensity of its neighbours, then it is classified as a ridgelet. These ridgelets are then connected together, according to a set of connectivity rules, to form tracks which are classed as ship tracks if they are long enough. The algorithm has been applied to two years of ATSR2 data. A month of results have been compared with other satellite datasets to validate the algorithm. There is a high ratio of false detections. Nevertheless the global distribution of ship tracks shows a similar pattern to the ship emissions distribution

A global ship track climatology from ATSR-2: January 1999 - January 2001

Two years (January 1999 - January 2001) of data from the Along-Track Scanning Radiometer 2 (ATSR-2) aboard the satellite ERS-2 have been processed with an automatic ship track detection algorithm. The distribution of detected tracks shows similar patterns and magnitudes to another satellite-derived dataset and is consistent with locations of shipping lanes. Most tracks are detected in the North Pacific and North Atlantic, between March and August. The derived track masks have been used with ATSR-2 data from the Oxford-RAL Aerosol and Clouds (ORAC) retrieval scheme to reveal differences between track and non-track clouds. Water clouds which are part of a ship track show an approximate 50% increase in optical depth as compared to background cloud conditions (30 km or more from tracks), and a decrease in effective radius of similar magnitude. This is consistent with the first aerosol indirect (Twomey) effect