Dianlei Wang

Snake venom proteins have attracted considerable attention as oral analgesics owing to their definite analgesic effects and lack of tolerance or addiction. Herein, we report the successful development of an optimized oral analgesic nanoparticle formulation (CS/ALG@NANT NPs), prepared by the self-assembly of chitosan/alginate and Naja atra neurotoxin (NANT) via polyelectrolyte complexation and optimized using a systematic Box-Behnken design. The resulting nanoparticles exhibited uniform spherical morphology, an appropriate particle size (278 nm), high encapsulation efficiency (>90%), and substantial drug loading (>23%). CS/ALG@NANT NPs showed pH-responsive stability, maintaining structural integrity under gastric conditions while enabling rapid intestinal release, as well as excellent cytocompatibility and time-dependent cellular uptake. In vivo imaging revealed strong intestinal targeting, prolonged retention, and minimal off-target distribution, thereby protecting NANT from gastric degradation. Pharmacodynamic studies demonstrated significant dose-dependent analgesic effects, with high-dose efficacy comparable to reference drugs. These findings indicate that CS/ALG@NANT NPs represent a promising oral delivery platform for sustained analgesia and enhanced intestinal targeting, offering strong potential for clinical pain management.

A newly identified polysaccharide, designated AMRP, was extracted and purified from traditional Chinese medicinal plant Atractylodes Macrocephalae Rhizoma (the rhizome of Atractylodis macrocephala Koidz.) collected from Qimen, Anhui Province. The structural characteristic of AMRP, its efficacy in alleviating ulcerative colitis (UC), and the underlying mechanisms regarding the enhancement of short-chain fatty acids (SCFAs) transport were thoroughly investigated. After purification, the structural formula of AMRP was identified as β-d-Fruf-[(2 → 1)-β-d-Fruf] n-(2 → 1)-α-d-Glcp. In vivo studies demonstrated that AMRP effectively mitigated colitis symptoms, including weight reduction, disease activity index, colon length, as well as pathological alterations within the colon. Further analyses showed that AMRP significantly reduced the concentrations of pro-inflammatory cytokines, including interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha, as well as the number of CD68+ inflammatory cells. With AMRP treatment, the content of the tight junction protein Claudin-1 was increased. Mechanistic investigations indicated that AMRP alleviates colitis symptoms by increasing SCFAs levels, upregulating the expression of monocarboxylate transporter 1 to facilitate the transport of butyric acid, and inhibiting the expression of histone deacetylase 2. Overall, these effects served to regulate the homeostasis of the colon immune system, achieving anti-inflammatory effects and improving the condition of UC.

Wilson's disease (WD) is a genetic disorder of copper metabolism that causes severe impairment of liver and brain functions, urgently requiring safe and effective chelation strategies. Herein, this work highlights the successful construction of a ROS-responsive nanoplatform (MIL-100(Fe)-DPA), which is facilely fabricated by encapsulating D-penicillamine (DPA) into the porous framework of MIL-100(Fe). The nanocomposite exhibits a stable crystalline structure, uniform nano size, excellent hemocompatibility, and high drug loading efficiency, while maintaining remarkable blood circulation stability. Importantly, its unique ROS-responsiveness enables targeted drug release under pathological copper-overloaded conditions, thereby achieving enhanced copper chelation and reduced systemic toxicity. In vivo studies demonstrate that MIL-100(Fe)-DPA markedly decreases hepatic copper accumulation, improves ALT and AST levels, restores hepatic architecture, and alleviates copper-induced tissue injury compared to free DPA. These attractive features indicate that MIL-100(Fe)-DPA represents a promising nanoplatform for precise copper chelation therapy, providing an effective therapeutic strategy for WD and related hepatic disorders.

Porous starch (PS) is widely used in food, pharmaceutical, and environmental industries for its high adsorption capacity and controlled release properties. To explore how surface gelatinization affected enzymatically prepared PS, corn starch was first modified via surface gelatinization using a CaCl₂ solution and then treated with α-amylase and amyloglucosidase to synthesize PS. Its structural and functional characteristics were subsequently analyzed. The findings demonstrated that the CaCl₂ solution facilitated the surface gelatinization and enhanced the enzymatic hydrolysis of natural starch. The yield, specific volume, water solubility, swelling power, and oil absorption capacity of PS pretreated with CaCl₂ solution were improved. After 40 min of processing, the yield, specific volume, and oil absorption capacity of PS reached the optimal state, increasing by 19.90%, 91.19%, and 32.84%, respectively. Consequently, its fisetin encapsulation efficiency (93.67%) and loading capacity (8.03%) were also higher than those of non-pretreated PS, attributed to the reduced short-range structure and crystallinity in the CaCl₂-pretreated PS. The DPPH and ABTS radical scavenging activities of CaCl₂-pretreated PS/fisetin (PS/FIT) exceeded those of the non-pretreated PS/FIT and free fisetin. These findings highlight the potential of CaCl₂ pretreatment as an effective strategy to enhance the functional properties of enzymatic PS.