Search

Background/Objectives: Indomethacin (IDM) is commonly used to treat chronic inflammatory diseases such as rheumatoid arthritis and osteoarthritis. However, long-term oral IDM treatment can harm the gastrointestinal tract. This study presents a design for encapsulating IDM within mixed micelles (MMs)-loaded dissolving microneedles (DMNs) to improve and sustain transdermal drug delivery. Methods: Indomethacin-loaded mixed micelles (IDM-MMs) were prepared from Soluplus® and Poloxamer F127 by means of a thin-film hydration method. The MMs-loaded DMNs were fabricated using a two-step molding method and evaluated for storage stability, insertion ability, in vitro release, in vitro transdermal penetration, and in vivo PK/PD studies. Results: The obtained MMs were stable at 4 °C and 30 °C for 60 days. The in vitro IDM transdermal penetration was remarkably improved by the MMs-loaded DMNs compared to a commercial patch. A pharmacokinetic study demonstrated that the MMs-loaded DMNs had a relative bioavailability of 4.1 in comparison with the commercial patch. Furthermore, the MMs-loaded DMNs showed a significantly shorter lag time than the commercial patch, as well as a more stable plasma concentration than the DMNs without MMs. The therapeutic efficacy of the IDM DMNs was examined in Complete Freund's Adjuvant-induced arthritis mice. The IDM DMN treatment effectively reduced arthritis severity, resulting in decreased paw swelling, arthritis index, spleen hyperplasia, and serum IL-1β and TNF-α levels. Conclusions: Our findings demonstrated that the novel MMs-loaded DMNs were an effective strategy for sustained IDM release, providing an alternate route of anti-inflammatory drug delivery. [ABSTRACT FROM AUTHOR]

Silk fibroin (SF) is an ideal material for microneedle (MN) preparation. However, long extraction and short storage durations limit its application. Furthermore, MNs prepared from SF alone are easy to break during skin insertion. In this study, a regenerated SF solution was autoclaved and freeze-dried to produce a stable and water-soluble SF sponge. The freeze-dried SF (FD-SF) solution was ultrasonically treated before being used in the fabrication of MNs. The ultrasonically modified SFMNs (US-SFMNs) were evaluated in comparison to FD-SFMNs made from FD-SF and conventional SFMNs made from regenerated SF. The results indicated that the FD-SF could be completely dissolved in water and remained stable even after 8 months of storage. FTIR and XRD analyses showed that SF in US-SFMNs had increased β-sheet content and crystallization compared to FD-SFMNs, by 7.3% and 8.1%, respectively. The US-SFMNs had higher mechanical strength than conventional SFMNs and FD-SFMNs, with a fracture force of 1.55 N per needle and a rat skin insertion depth of 370 μm. The US-SFMNs also demonstrated enhanced transdermal drug delivery and enzymatic degradation in vitro. In conclusion, the autoclaving and freeze drying of SF, as well as ultrasonication-induced MN preparation, provide promising SF-based microneedles for transdermal drug delivery. [ABSTRACT FROM AUTHOR]

Objective: To explore the transitive regularity of holistic constituents from the crude slices of the medicinal raw materials (MCS) to the formula granules (FG), fufang decoction (FD), and finally, the concentrated pills (CP) of Liuwei Dihuang Fufang (六味地黄复方, LWDHF). Methods: Samples for MCS, FG, FD, and CP of LWDHF were obtained, and a fingerprint database was established using high-performance liquid chromatography (HPLC), by separating the samples in an XB-C18 column and analyzing the transitive regularity of components using the total quantum statistical moment (TQSM), including total quantum zero moment (AUCT), total quantum first moment (MRTT), total quantum second moment (VRTT), and its similarity approach. The AUCT, MRTT, and VRTT were calculated based on the representative HPLC chromatograms of FG, FD, and CP of LWDHF. Results: AUCT of FG, FD, and CP of LWDHF was 71 804, 46 553, and 144 646 μV s, respectively; MRTT was 14.43, 14.54, and 18.85 min, respectively; and VRTT was 106.98, 112.84, and 269.12 min2, respectively. Comparing the similarity of FG/FD, FG/CP and FD/CP of LWDHF, the TQSM similarity values were 98.66%, 76.62%, and 75.37%, respectively, whereas the traditional similarity evaluation values were 98.68%, 85.43%, and 85.60%, respectively. Conclusion: The results perform little distinction in the total composition between FG and FD, whereas some distinction existed between FD and CP. Experimental evidence, therefore indicates that FG could be used as the alternative of MCS in clinical applications.

Summary: The study inquired the influences of l‐arginine and l‐lysine on the physicochemical properties (including weight loss rate, water activity, texture, colour, lipid and protein oxidation, residual nitrite content and total volatile basic nitrogen (TVB‐N) content) of low‐sodium and low‐phosphate Cantonese sausage during the 1‐ and 7‐day storage. The results showed that the addition of l‐arginine or l‐lysine reduced the weight loss rate, TBARS content, carbonyl group content and residual nitrite level, slightly decreased water activity, and enhanced L*, a* and b* values. Compared to the control, 0.3% l‐arginine or l‐lysine declined hardness and chewiness, while 0.6% l‐arginine or l‐lysine elevated these two parameters. However, the addition of l‐arginine or l‐lysine also led to an increase in TVB‐N content. Overall, l‐arginine and l‐lysine improved the qualities of low‐sodium and low‐phosphate Cantonese sausage, which might be attractive to meat product manufacturers. [ABSTRACT FROM AUTHOR]

As power big data plays an increasingly important role in the operation, maintenance, and management of power systems, complex and covert false data attacks pose a serious threat to the safe and stable operation of the power system. This article first explores the characteristics of new power systems, and the challenges posed by false data attacks. The application of big data technology in power production optimization, energy consumption analysis, and user service improvement is then investigated. The article classifies typical attacks against the four stages of power big data systems in detail and analyzes the characteristics of the attack types. It comprehensively summarizes the attack detection technologies used in the four key stages of power big data, including state estimation, machine learning, and data-driven attack detection methods in the data collection stage; clock synchronization monitoring and defense strategies in the data transmission stage; data processing and analysis, data integrity verification and protection measures of blockchain technology in the third stage; and traffic supervision, statistics and elastic computing measures in the control and response stage. Finally, the limitations of attack detection mechanisms are proposed and discussed from three dimensions: research problems, existing solutions, and future research directions. It aims to provide useful references and inspiration for researchers in power big data security to promote technological progress in the safe and stable operation of power systems. [ABSTRACT FROM AUTHOR]