Jiangsu Kanion Pharmaceutical Co., Ltd.

Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening reaction associated with dopamine antagonists, particularly typical antipsychotics. Despite the relatively low incidence of NMS linked to atypical antipsychotics (AAPs), there is a notable lack of extensive real-world studies investigating this condition.

This study utilizes data from the FDA Adverse Event Reporting System (FAERS) from 2004 to 2024, employing disproportionality analysis to explore the association between fourteen commonly prescribed AAPs and NMS. Multivariate logistic regression was conducted to identify risk factors for mortality related to NMS.

We analyzed 79,980 primary suspected adverse drug event (ADE) reports for NMS, revealing a slight male predominance and a median age of 48 years (Interquartile Range [IQR]: 31-64). Patients were primarily located in Europe and the United States. Ziprasidone exhibited the strongest pharmacovigilance signal (Reporting Odds Ratio [ROR] = 3.09; 95 % confidence interval [CI]: 2.97-3.21), while lurasidone showed the lowest signal strength (ROR = 1.58; 95 % CI: 1.52-1.65). The median time to onset of NMS was 42 days (IQR: 9-328.25). Significant mortality risk factors included age ≥ 65 years (Odds Ratio [OR] = 4.45; 95 % CI: 3.33-5.95), Parkinson's disease (OR = 32.69; 95 % CI: 14.75-72.46), and malignant hyperthermia (OR = 25.23; 95 % CI: 8.62-73.83), with an area under the curve (AUC) of 0.877.

This study provides vital pharmacovigilance insights regarding NMS related to AAPs, enhancing the understanding of its clinical implications.

Gastrodin (GA) and ferulic acid (FA) are the main active ingredients of the traditional Chinese medicine Da Chuan Xiong formula for migraine treatment. This study aimed to develop a gastrodin-ferulic acid co-loaded liposomal gel patch (GA/FA-Lip-GelP) as a transdermal drug delivery system (TDDS) for migraine management.

TDDS overcomes the limitations of first-pass metabolism associated with oral administration and is particularly suitable for migraine patients experiencing nausea and vomiting. The system contains three key components: sodium polyacrylate (hydrophilic gel matrix), laurocapram (Azone, permeation enhancer), and GA/FA-loaded liposomes (nanocarrier). This combination enables effective systemic drug delivery.

The GA/FA-Lip was prepared using central composite design optimization. Subsequently, the GA/FA-Lip-GelP formulation was developed through single-factor screening and Box-Behnken designs. The optimized GA/FA-Lip-GelP was systematically evaluated via in vitro release studies, ex vivo transdermal permeation experiments, and in vivo pharmacokinetic/pharmacodynamic analyses.

The GA/FA-Lip was prepared via thin-film dispersion, forming uniform spherical nanoparticles (146.34 ± 1.35 nm). These nanoparticles achieved high encapsulation efficiencies (GA: 85.26 ± 1.90%; FA: 86.92 ± 2.23%) and demonstrated excellent stability. The final GA/FA-Lip-GelP demonstrated optimal adhesion, sustained drug release, and content uniformity under low-temperature storage. Compared to oral administration and non-liposomal gel patches, GA/FA-Lip-GelP showed significantly enhanced transdermal permeation, improved pharmacokinetic profiles, and superior therapeutic efficacy.

GA/FA-Lip-GelP demonstrated potential as an effective migraine treatment by overcoming first-pass metabolism, thereby improving bioavailability and enabling sustained drug release.

Fisetin exhibits diverse bioactivities but faces application limitations due to poor stability and bioavailability. Glycosylation effectively addresses these challenges. In this study, a novel glycosyltransferase gene (CeUGT) was identified from Cichorium endivia L. and heterologously expressed in Escherichia coli (E. coli). Substrate spectrum analysis revealed that CeUGT effectively catalyzes the glycosylation of various flavonoids containing a 3'-OH group, as well as representative phenolic acids and stilbenes. Biochemical characterization of CeUGT toward fisetin was performed. Through the construction of engineered bacteria and under optimal fermentation conditions including TB medium containing 10 g/L glycerol as the carbon source, with the addition of 0.1 mM IPTG, 20 °C induction temperature, 10 g/L cellobiose, 2.5 % (v/v) DMSO, 2 g/L fisetin, and 30 °C fermentation temperature, a maximum titer of 3.069 g/L was achieved with a conversion rate of 98 %. The novel, highly efficient, and regioselective flavonoid-3'-O-glycosyltransferase (3'GT) discovered in this study represents the first reported enzyme capable of specifically glycosylating the 3'-OH position of fisetin. Its broad substrate spectrum and high catalytic efficiency provide an excellent biocatalyst for glycosylating other natural flavonoids with 3'-OH groups. Additionally, this study offers valuable technical insights for the efficient production of rare, high-value flavonoid glycoside derivatives through in vivo metabolic engineering approaches.