Times Higher Retention Research Articles

Optimisation and Characterisation of Improved Nanoemulsion Formulations Containing Ceramide 3

AbstractCeramide3 (Cer3) is one of the important components of stratum corneum (SC) lipids with good moisturizing and repairing properties. However, it suffers from (a) poor solubility, (b) easy crystallization and precipitation, and (c) strong polarity and difficulty in transdermal application. This study aimed to load Cer3 into nanoemulsions (NEs) to overcome these mentioned defects. The optimized NEs formulation was prepared by high pressure homogenization method and characterized by several methods. The optimized ceramide3 nanoemulsions (Cer3‐NEs) exhibited a good physico‐chemical stability over 3 months under different conditions, with droplet size of 103.1 nm, PDI of 0.178, zeta potential of −39.09 mV, pH of 6.20 and encapsulation efficiency of 96.39 %. Turbiscan results showed that formulations containing Cer3‐NEs have better stability than those containing free Cer3. The dermal delivery ability of Cer3‐NEs was assessed by Franz diffusion and confocal Raman spectroscopy (CRM). In vitro and in vivo penetration studies showed that Cer3‐NEs serum have almost 2–3 times higher retention in the skin and permeation in the receptor solution compared to serum with free Cer3. The findings show NE is a promising carrier of Cer3 for topical administration in the treatment of dryness and barrier damage due to higher stability and better skin permeability.

A Radiolabeling Method for Precise Quantification of Polymers

Radiolabeling a protein, molecule, or polymer can provide accurate and precise quantification in biochemistry, biomaterials, pharmacology, and drug delivery research. Herein, we describe a method to 125I label two different polymers for precise quantification in different applications. The surfaces of model contact lenses were modified with phenylboronic acid to bind and release the natural polymer, hyaluronic acid (HA); HA uptake and release were quantified by radiolabeling. In the second example, the in vivo distribution of a mucoadhesive micelle composed of the block copolymer of poly(lactide)-b-poly(methacrylic acid-co-acrylamidophenylboronic acid) was investigated. The presence of phenyl boronic acid groups (PBA), which bind to mucosal surfaces, was proposed to improve the retention of the micelle. 125I labeling of polymers was examined for quantification of microgram amounts of HA present on a contact lens or to evaluate the enhanced retention of PBA micelles on mucosal surfaces in vivo. The introduction of phenol groups onto the polymers allowed for the labeling. HA was modified with phenol groups through a coupling reaction of its carboxylic acid with hydroxybenzylamine. Phenol functional block copolymer micelles with and without PBA were synthesized by including N-(4-hydroxyphenethyl)acrylamide during polymerization. The phenol groups of HA and the block copolymers were labeled with 125I using a modified ICl labeling method. 125I labeling enabled quantification of HA loading and release including the effect of varying amounts of PBA on the contact lens surfaces. Micelles made from 125I-labeled block copolymers with and without PBA were administered intranasally to Brown Norway rats. The animals were sacrificed either immediately after or 4 h after their last nasal instillation, and the nasopharyngeal tissues were removed and quantified. Radioactivity measurements demonstrated that the presence of the PBA mucosal binding groups led to approximately four times higher retention. The HA and block copolymer 125I labeling presented in this article demonstrates the utility of the method for quantification and tracking of microgram quantities of polymers in diverse applications.

Morphology-Dependent Ambient-Condition Growth of Perovskite Nanocrystals for Enhanced Stability in Photoconversion Device.

CsPbBr3 perovskite nanocrystals with two different dimensionalities were synthesized at different temperatures and then integrated as optoelectronic transducers into transistor-type photoconversion devices. Postsynthesis transformation was observed for two-dimensional (2D) nanoplatelets, while the transformation was rarely found in 3D nanocubes. At ambient temperature and pressure, neighboring nanoplatelets made facet-to-facet contact and then fused into larger 2D nanoplatelets (2-5 times) without defects. The coalescence of 2D nanoplatelets at the ambient condition lowered the density of defects at the surface of the nanocrystals and thus could facilitate effective and stable photoconversion behavior in the nanocrystal film integrated into the device. Consequently, the ambient-condition aging of 2D nanoplatelets on device substrate led to 3 times higher retention in photoconversion performance. Importantly, these results provide a new concept of how perovskite nanocrystals can be integrated into a device for enhanced stability in device performance.

NAND flash memory device with ground plane in buried oxide for reduced short channel effects and improved data retention

In this work, we investigate a promising technique for improving the performance of silicon-on-insulator (SOI) silicon-oxide-nitride-oxide-silicon (SONOS) NAND flash memory cells with ground plane in buried oxide (GPB). The physical phenomena that potentially degrade the performance of NAND flash memory cells at lower gate length are controlled by selection of an appropriate NAND flash device architecture. The various attributes of SONOS memory cells with GPB are compared with conventional SOI SONOS memory devices. It is shown that at the scaled gate length of 25 nm, a flash memory cell with GPB limits the short channel effects and achieves ~ 103 times higher memory speed. The short channel performance is evaluated by considering subthreshold slope (SS) and drain-induced barrier lowering (DIBL) parameters, which show significant improvement in SS along with relatively lower DIBL values at lower gate lengths in SONOS cells with GPB. The results highlight that a ~ 1.3 times wider memory window and ~ 2.4 times higher retention can be obtained over a period of 10 years in a SONOS GPB device in comparison to the SOI SONOS memory device. The present work provides guidelines to design highly dense flash memory devices while achieving improved reliability without altering the gate stack.

Drug-fortified liposomes as carriers for sustained release of NSAIDs: The concept and its validation in the animal model for the treatment of arthritis

Drug-fortified cationic liposomes of 6‑methoxy‑2‑naphthylacetic acid (6‑MNA) were prepared and characterized by various techniques. The residence time of drug-fortified liposomes in joint cavity was evaluated by intra-articular (IA) administration of the radio-labeled (99mTc) liposomal formulation in the inflamed joints in rats. The cationic liposomal formulation composed of 6‑MNA (3) as an active agent, its double salt (4) with the lipid 1,2‑distearoyl‑sn‑glycero‑3‑phosphoethanolamine (DSPE), and pharmaceutically acceptable excipients such as hydrogenated soyabean phospatidylcholine (HSPC) and 1,2‑dioleyloxy‑3‑trimethylammoniumpropane chloride (DOTAP) were developed using thin film hydration technique. The cryo-TEM analysis confirmed that the prepared optimized liposomal formulation (DFL-2) was a mixture of small unilamellar vesicles (SUVs), large unilamellar vesicles (LUVs) and multilamellar vesicles (MLVs). In addition, the TEM analysis confirmed that the prepared liposomes were of spherical in shape having liposome size in the range of 500–900 nm and zeta potential of about +30 mV. The developed cationic liposomes exhibited sustained release profile of payload of 6‑MNA for over >12 h and about five times higher retention in the inflamed animal joints after 24 h (by scintigraphy of the joints) as compared to the plain 6‑MNA solution when administered by IA route. The anti-inflammatory activity of prepared liposomal composition is evaluated by Freund's adjuvant induced arthritic model in rats. The liposomal formulation was well tolerated by all animals indicating good biocompatibility. Further, the cationic liposomal formulation treated group showed decreased erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level in comparison to the control and the standard groups in the in vivo study. The improved efficacy of the drug-fortified liposomal formulation was due to the coupled effect of longer retention and sustained release of the active drug 6‑MNA in the joints. From the obtained results it could be concluded that the combined effect of the cationic charge on the drug-fortified liposomes and the inherent affinity of the active agent towards the synovial joint tissues, coupled with slow release of the active drug due to double salt approach at the site of administration could potentially decrease the frequency of IA drug administration. Hence such a formulation could prove to be a therapeutic boon for the management of late stage arthritis.