Although berberine has notable anti-inflammatory and antioxidant effects for ulcerative colitis (UC) treatment, its clinical application is limited by poor oral bioavailability. To improve berberine delivery, we developed colon-targeted mucoadhesive Eudragit® S100/Bletilla striata polysaccharide (EB)-coated microspheres (MPs) encapsulating berberine hydrochloride (BH)-hydrogenated soy phosphatidylcholine (HSPC) complex. BSP acts as both a bioadhesive carrier for prolonged mucosal retention and an immunoregulatory agent synergizing with berberine. Fabricated via electrospray and fluidised-bed coating, the formulation realized pH-responsive colon-specific release. In vitro studies, it showed favorable pH-dependent release, scavenged reactive oxygen species, and promoted M2 macrophage polarization. Small animal fluorescence imaging studies have confirmed its colon-targeting and mucoadhesive properties. In DSS-induced acute and FXY-DSS-induced chronic colitis models, EB@BH-HSPC significantly alleviated inflammation, restored intestinal barrier function, and reduced oxidative stress, with improved therapeutic effects attributed to berberine-BSP synergy and integrated delivery advantages. BSP serves as both film-forming adhesive component and synergistic therapeutic component, making this system a potent strategy for UC treatment.

In colorectal cancer, the cancer-immunity cycle is often disrupted by the lack of effective tumor-associated antigens, impaired activation of antigen-presenting cells, and insufficient T cell infiltration, leading to tumor immune escape and disease progression. Therefore, we developed PTX-GLSO SEDDS@GLS (PGS@GLS), a multicomponent solid self-emulsifying drug delivery system (SEDDS) incorporating paclitaxel (PTX) and Ganoderma lucidum spore oil (GLSO), with processed Ganoderma lucidum spores (GLS) as the solid carrier. The intestinal lymphatic absorption of PTX-GLSO SEDDS was significantly enhanced after GLS solidification, facilitating the induction of immune responses. Additionally, the oil phase of GLSO enhanced PTX solubility through self-emulsification into nanoemulsion. In tumors and the mesenteric lymphatic system, PGS@GLS induced robust immunogenic cell death and triggered the release of damage-associated molecular patterns, thereby initiating the cancer-immunity cycle. Furthermore, GLSO and GLS synergistically promoted dendritic cell maturation and cytotoxic T cell activation, thereby potentiating anti-tumor immune responses. Tumor cells were killed by the accumulated cytotoxic T cells, and the resulting dead tumor cells released additional tumor-associated antigens, which were subsequently presented by dendritic cells, creating a positive feedback loop to amplify the cancer-immunity cycle. Notably, PGS@GLS maintained potent antitumor efficacy while mitigated PTX-related systemic toxicity, representing a promising oral chemoimmunotherapy platform that restores antitumor immunity through lymphatic transport-mediated cancer-immunity cycle reinforcement.

Sweeping proinflammatory factors has shown critical potential for curing inflammatory diseases. Hence, it is promising to explore a synergistic strategy combining colon-targeting drug delivery and proinflammatory factor scavenging for better management of inflammatory bowel disease (IBD). Herein, we constructed a colon-targeting nanoplatform by hybridizing an inorganic carrier, mesoporous silica nanoparticle (MSN) with an organic cationic functional polymer polyethyleneimine (PEI), and an anionic coating, Eudragit. The resultant nanoplatform exhibits uniform size, improved drug loading, on-demand drug release, and effective colon-targeting and retention capabilities via surface charge flip. Importantly, it can selectively release the loaded aminosalicylate prodrug olsalazine sodium (OLZ) in simulated colonic fluid while regulating macrophage polarization by binding and scavenging proinflammatory anionic cfDNA through electrostatic interaction with the exposed cationic PEI. Meanwhile, it alleviates the mucosal barrier damage of intestinal epithelial cells. Benefiting from its satisfactory attributes, this nanoplatform has been successfully applied in the treatment of colitis in a mouse model, demonstrating a significant protective effect on the intestinal mucosa. These results confirmed that it is promising for better IBD management to employ the synergistic intervention strategy integrating colon-targeting drug therapy and proinflammatory cfDNA scavenging.

Background/Objectives: Xu Chunfu’s Modified Xianglian Pill (XXLP) has been used for centuries in Chinese medicine to treat “diarrhea” and “dysentery,” conditions analogous to modern ulcerative colitis (UC). However, the scientific basis for its efficacy and mechanisms remains unclear. Methods: The chemical composition of XXLP was analyzed via UPLC-ESI-MS/MS. A colitis mouse model was established using DSS, and the therapeutic effects were assessed based on body weight, disease activity index (DAI), colon length, and histopathology. Inflammatory cytokines were measured using ELISA. Proteomic analysis and molecular docking identified key targets, which were validated using LPS-induced HT-29 cells via Western blot (WB), qRT-PCR, immunofluorescence (IF), and transmission electron microscopy (TEM). Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Results: Analysis of XXLP led to the detection of 373 compounds. XXLP significantly improved colitis symptoms, including weight loss and colon shortening, and reduced the concentrations of inflammatory markers IL-1β, IL-18, TNF-α, and IL-6. Proteomics and molecular docking identified NADPH oxidase 2 (NOX2) as a key target of XXLP intervention in mice with colitis. qRT-PCR, WB, IF, and TEM results further confirmed that XXLP effectively suppressed the expression of NOX2 and its associated protein levels. Sequencing analysis of 16S rRNA showed that XXLP significantly increased the relative abundance of beneficial bacterial genera (Muribaculaceae and Ruminococcaceae) while markedly reducing the levels of harmful bacteria (Enterobacteriaceae). Correlation analysis revealed that specific microorganisms were correlated with NOX2-related protein expression and severity of colonic inflammation. Conclusions: XXLP effectively alleviates colitis by suppressing inflammatory responses. Its mechanism involves regulating the NOX2/ROS/mitochondria/NLRP3 axis and altering gut microbiota composition, providing novel insights for colitis treatment.

Cancer remains a leading cause of death worldwide. Colorectal cancer (CRC) is the most common type of gastrointestinal malignancy, with the combined effect of multiple etiological factors. Multifunctional nanocomposites present a promising platform for synergistic therapy of CRC. Elemene (EL), an active component in traditional Chinese medicine, exhibits both antitumor and immunostimulatory activities. However, its clinical application is limited by poor stability, low tumor accumulation, and the difficulty of effectively harnessing its dual activities. Herein, we developed an orally administered, colon-targeted nanoemulsion, LMP@EL-CNE, comprising EL cationic nanoemulsions (EL-CNE) armored with a low-methoxyl pectin (LMP) polysaccharide shell. This system exhibits dual responsiveness to colonic microflora enzymes and pH, allowing for prolonged retention and targeted drug release in the colon. Subsequently, it generates ultra-small EL nanodroplets (∼20 nm), which enhance tumor penetration and accumulation. Notably, LMP@EL-CNE induces mitochondrial dysfunction and downregulates glutathione peroxidase 4 (GPX4), a key regulator of ferroptosis. This disruption of the balance unlocks a more potent ferroptosis response, amplifying EL's intrinsic activity in CT26 cells. In an in vivo orthotopic CRC model, LMP@EL-CNE exhibited potent anti-tumor activity and activated anti-tumor immunity, manifesting as a "hot" tumor microenvironment, outperforming the EL commercial preparation. Furthermore, this polysaccharide-armored nanoemulsion has been proven to restore gut homeostasis by repairing damaged epithelial barriers and reshaping the gut microbiota. In conclusion, we propose a novel nano-platform that integrates multiple functions to induce ferroptosis, activate anti-tumor immunity, and restore gut homeostasis, providing a comprehensive and effective strategy for colorectal cancer treatment. Chemical compounds studied in this article:Elemene (EL CAS No. 33880-83-0) the primary active pharmaceutical ingredient (API) with antitumor activity Polyoxyethylene hydrogenated castor oil (RH40, CAS No. 61788-85-0), a key non-ionic surfactant for nanoemulsion stabilization.Hexadecyl trimethyl ammonium bromide (CTAB, CAS No. 57-09-0), a cationic surfactant used in the nanoemulsion formulation.Low-methoxyl pectin (LMP, CAS No. 9000-69-5), an anionic polysaccharide constituting the functional "armor" of the nanoemulsion.Liproxstatin-1 (Lip-1, CAS No. 950455-15-9), a potent ferroptosis inhibitor used for mechanistic validation.Glutathione (GSH, reduced form, CAS No. 70-18-8), a central antioxidant, quantified to assess the status of the GPX4-mediated ferroptosis defense system.Malondialdehyde (MDA, CAS No. 542-78-9), the primary end-product of lipid peroxidation, quantified as a key indicator of ferroptosis.

Due to the existence of the blood-brain barrier (BBB) and the complicated pathological mechanisms of Alzheimer's disease (AD), current therapeutic approaches for AD show limited efficacy. To overcome these challenges, a multi-strategy drug delivery system (SA-BP-MB/BBR NPs) was developed: photothermal conversion polydopamine nanoparticles (PDA NPs) were decorated with sialic acid-modified bovine serum albumin (SA-BSA) to prepare SA-modified and BSA-stabilized PDA NPs (SA-BP NPs) for targeting the BBB and co-loaded with photosensitizer methylene blue (MB) and berberine (BBR) to target multiple neuropathological factors, including Aβ aggregation and tau hyperphosphorylation. The prepared SA-BP-MB/BBR NPs had spherical morphology with a uniform particle size of 143.43 nm and PDI of 0.095. Drug loading capacities were 6.98 % for MB and 3.50 % for BBR. Our investigations demonstrated that the cellular uptake efficiency of biocompatible SA-BP-MB/BBR NPs increased by 1.74 times when combined with photothermal and photodynamic therapy, which effectively inhibited Aβ aggregation, Aβ fibril depolymerization, and tau hyperphosphorylation. Pharmacokinetics and in vivo biodistribution studies revealed a higher area under the curve (AUC0-t) of SA-BP-MB/BBR NPs (9.75 and 7.52 times higher) than free MB and BBR, and SA modification promoted brain accumulation. Overall, SA-BP-MB/BBR NPs have the potential to be an effective treatment for AD.

Solid self-microemulsifying drug delivery systems (SMEDDS) offer unique advantages over conventional liquid formulations, including enhanced physical stability, simplified storage/transportation, and improved drug delivery efficiency. In this study, we developed a paclitaxel (PTX)-loaded SMEDDS using Ganoderma lucidum spore oil (GLSO) as a multifunctional oil phase. Through formulation screening and optimization, the PTX-GLSOSMEDDS was successfully converted into a solid powder. Solid-state analyses confirmed the amorphous dispersion of PTX within the matrix, while the powder exhibited favorable fluidity, stability, and rapid in vitro drug release kinetics. PTX-GLSO-SMEDDS demonstrated potent antitumor effects by inducing apoptosis and suppressing metastasis in colorectal cancer (CRC) cells. In vivo studies revealed dual therapeutic advantages: enhanced tumor suppression and synergistic immunomodulation via GLSO-mediated activation of tumorassociated cytotoxic T lymphocytes regulation. Notably, the formulation reduced systemic toxicity compared to conventional PTX injections. By integrating GLSO's inherent bioactivity with SMEDDS technology, this work establishes a robust platform that synergizes chemotherapy and immunotherapy, offering a clinically translatable strategy for CRC treatment with improved safety and therapeutical outcomes. The findings underscore GLSO's potential as a natural, multifunctional excipient for advanced drug delivery systems.

Correction for ‘Development of a novel UHPLC-UV combined with UHPLC-QTOF/MS fingerprint method for the comprehensive evaluation of Nao-Luo-Xin-Tong: multi-wavelength setting based on traditional Chinese medicinal prescription composition’ by Lina Wang et al. , Anal. Methods , 2019, 11 , 6092–6102, https://doi.org/10.1039/C9AY01975H.

Ginsenoside Rg-3 (G-Rg3) is a traditional Chinese medicine monomer that enhances immune function, inhibits tumor cell infiltration and metastasis, and promotes tumor cell apoptosis. Peony Seed Oil (PSO), an edible vegetable oil rich in n-3 polyunsaturated fatty acids, can enhance the fluidity of tumor cell membranes, thereby facilitating the uptake of anti-tumor medications and improving their therapeutic efficacy. Additionally, alpha-linolenic acid in n-3 polyunsaturated fatty acids can induce apoptosis and inhibit the invasion and metastatic ability of tumor cells. In this study, based on the principle of "combining drug and adjuvant," PSO was used to replace the traditional oil phase in the preparation of G-Rg3/PSO solid self-microemulsifying drug delivery system (G-Rg3/PSO-SSMEDDS). By encapsulating the solid self-microemulsion into colon-targeting capsules, the drug is able to specifically target the colon, where PSO and G-Rg3 exert a synergistic anti-tumor effect, thereby enhancing the therapeutic efficacy. The results indicate that there were no significant changes in morphology or particle size before and after the self-microemulsion solidification, while the solubility of G-Rg3 was notably improved, further contributing to its overall therapeutic potential. In vitro and in vivo anticancer studies have validated this synergistic effect, demonstrating that G-Rg3/PSO-SSMEDDS significantly inhibits tumor cell proliferation and metastasis, promotes tumor cell apoptosis, and exhibits potent anticancer activity in both in vitro and in vivo models. The substitution of PSO for the traditional oil phase in the emulsion presents a promising strategy for the utilization of PSO, which has broad research value and application potential.

Drug resistance has emerged as a great challenge for achieving satisfactory therapeutic efficacy in platinum-based chemotherapy. Specifically, we synthesized a series of host defense peptide mimics with different degrees of polymerization (DP), i.e., poly(ethylene glycol)-poly(2-azepane ethyl methacrylate) (PEG45-PAEMAn, n = 8, 20, 43, 87, and 183), which displayed DP- and pH-dependent plasma membrane-disruptive capability and antitumor activity. Among these, PEG45-PAEMA43 exhibited the highest cytotoxicity at tumor acidity (pH 6.7), selectivity index, and in vivo antitumor activity, and was selected to encapsulate the hydrophobic Pt(IV) prodrug to form the PEG-PAEMA-Pt(IV) nanoprodrug. The nanoprodrug boosted the membrane-disruptive capability and antitumor activity of A549 and cisplatin-resistant A549/DDP cells at tumor acidity. Notably, it exhibited a much higher cellular uptake for A549/DDP cells and in vivo antitumor activity than PEG-PAEMA or cisplatin alone. This indicated that the PEG-PAEMA-Pt(IV) nanoprodrug could break the drug diffusion barrier posed by the cell membrane and disable even reverse efflux resistance.

Due to the poor solubility, permeability, stability and tumor-targeting ability of norcantharidin (NCTD), currently commercially available NCTD formulations require patients to take the medicine more frequently. Moreover, the formulation of NCTD themselves have certain toxicity, thus showing unsatisfactory therapeutic outcomes and serious systemic side effects. Based on the specific acidic environment at the tumor site, in this study, the pH-sensitive NCTD solid self-microemulsion (NCTD@CS-DMMA SSME) was prepared by introducing 2,3-dimethylmaleic acid amide modified chitosan (CS-DMMA), and it was wrapped in colon-coated capsule to achieve stable and controlled drug release in the acidic environment of colonic tumors. After self-emulsification, it had a particle size of 75.88 ± 0.85 nm and carried a negative charge. Under the condition of pH 6.5, NCTD@CS-DMMA SSME exhibited first-order release kinetics characteristics. Moreover, the cumulative release under the condition of pH 6.5 was 2.04-fold higher than that under the condition of pH 7.4. The in situ intestinal absorption assay elucidated that the prepared formulation could effectively improve the absorption rate constant and apparent permeability coefficients of NCTD in colon tumor site. The antitumor effect in vivo and in vitro showed that it could not only improve the inhibition ability of tumor growth, migration and invasion in mice, but also increase the tumor-infiltrating T lymphocytes in mice with colon cancer, thus inhibiting tumor growth. In summary, the NCTD@CS-DMMA SSME can deliver drugs to the site of colon tumors and continuously release drugs, providing new insights into improving the treatment effectiveness of colon cancer.

Norcantharidin (NCTD), a promising anti-tumor agent, is limited by poor water solubility and low oral bioavailability. This study aimed to formulate NCTD into a self-emulsifying drug delivery system (SEDDS) to enhance its oral bioavailability and elucidate the underlying mechanisms. Six NCTD-loaded SEDDS formulations with droplet sizes ranging from 50 nm to 200 nm and different surface charges were prepared. These formulations were characterized, and the impact of digestion on drug solubility was evaluated through in vitro lipolysis. The effects of droplet size and surface charge on cellular uptake were investigated using in vitro cell experiments. Intestinal permeability was evaluated using a Caco-2 cell monolayer model, with apparent permeability coefficients and trans-epithelial electrical resistance (TEER) changes monitored. The oral bioavailability of different SEDDS formulations was clarified by in vivo pharmacokinetics and the influence of surface charge on lymphatic absorption was examined through in vivo distribution studies. Results showed that reducing droplet size and modifying droplets to carry a positive charge significantly enhanced NCTD's oral bioavailability by improving cellular uptake, intestinal permeability, and modulating lymphatic absorption. These findings provide valuable insights for the design of effective oral nanoformulations of NCTD.

Although the combination of anti-vascular strategy plus immunotherapy has emerged as the optimal first-line treatment of hepatocellular carcinoma, lack of tumor targeting leads to low antitumor efficacy and serious side effect. Here, we report an ultra-pH-sensitive nanoparticle of gambogenic acid (GNA) encapsulated by poly(ethylene glycol)-poly(2-azepane ethyl methacrylate) (PEG-PAEMA) for tumor-targeting combined therapy of anti-vascular strategy plus immunotherapy. PEG-PAEMA-GNA nanoparticle was quite stable at pH 7.4 for 30 d. In contrast, it exerted size shrinkage, charge reversal and the release of GNA at pH 6.7 within 24 h. Moreover, PEG-PAEMA-GNA significantly enhanced the anti-vascular activity, membrane-disruptive capability and pro-apoptosis when pH changed from 7.4 to 6.7. Western blot analysis exhibits that PEG-PAEMA and its GNA nanoparticle facilitated the phosphorylation of STING protein. In vivo assays show that PEG-PAEMA-GNA not only displayed much higher tumor inhibition of 92 % than 37 % of free GNA, but also inhibited tumor vasculature, promoted the maturation of dendritic cells and recruited more cytotoxic t-lymphocytes for sufficient anti-vascular therapy and immunotherapy. All these results demonstrate that PEG-PAEMA-GNA displayed tumor-targeting combined treatment of anti-vascular therapy and immunotherapy. This study offers a simple and novel method for the combination of anti-vascular therapy and immunotherapy with high selectivity towards tumor.

The homogeneous galactoglucan PCP-1C extracted from Poria cocos sclerotium has multiple biological activities. The present study demonstrated the effect of PCP-1C on the polarization of RAW 264.7 macrophages and the underlying molecular mechanism. Scanning electron microscopy showed that PCP-1C is a detrital-shaped polysaccharide with fish-scale patterns on the surface, with a high sugar content. The ELISA assay, qRT-PCR assay, and flow cytometry assay showed that the presence of PCP-1C could induce higher expression of M1 markers, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-12 (IL-12), when compared with the control and the LPS group, and it caused a decrease in the level of interleukin-10 (IL-10), which is the marker for M2 macrophages. At the same time, PCP-1C induces an increase in the CD86 (an M1 marker)/CD206 (an M2 marker) ratio. The results of the Western blot assay showed that PCP-1C induced activation of the Notch signaling pathway in macrophages. Notch1, ligand Jagged1, and Hes1 were all up-regulated with the incubation of PCP-1C. These results indicate that the homogeneous Poria cocos polysaccharide PCP-1C improves M1 macrophage polarization through the Notch signaling pathway.

The membrane-disruptive strategy, which involves host defense peptides and their mimetics, is a revolutionary cancer treatment based on broad-spectrum anticancer activities. However, clinical application is limited by low selectivity towards tumors. In this context, we have established a highly selective anticancer polymer, i.e. poly(ethylene glycol)-poly(2-azepane ethyl methacrylate) (PEG-PAEMA), that can mediate the membrane-disruptive activity via a subtle pH change between physiological pH and tumor acidity for selective cancer treatment. Specifically, the resulting PEG-PAEMA can assemble into neutral nanoparticles and silence the membrane-disruptive activity at physiological pH and disassemble into cationic free-chains or smaller nanoparticles with potent membrane-disruptive activity after the protonation of the PAEMA block due to tumor acidity, resulting in high selectivity towards tumors. Dramatically, PEG-PAEMA exhibited a >200-fold amplification in hemolysis and <5% in IC50 against Hepa1-6, SKOV3 and CT-26 cells at pH 6.7 as compared to those at pH 7.4, thanks to the selective membrane-disruptive mechanism. Moreover, mid- and high-dose PEG-PAEMA demonstrated higher anticancer efficacy than an optimal clinical prescription (bevacizumab plus PD-1) and, significantly, had few side effects on major organs in the tumor-bearing mice model, agreeing with the highly selective membrane-disruptive activity in vivo. Collectively, this work showcases the latent anticancer pharmacological activity of the PAEMA block, and also brings new hope for selective cancer therapy.

人才是第一资源,创新是第一动力,培养高质量的创新型人才是高校人才培养的主要目标,科教融合理念是新时代高等教育的核心育人理念,是培养创新型人才的重要途径.以安徽中医药大学为例,以促进中医药传承发展为导向,基于科教融合理念,分析中医药院校本科人才培养过程中科教融合面临的问题和挑战,探索科教协同育人体制机制,深入推进科教融合,更好地服务地方特色高水平大学建设和争创"双一流"学科.

Self-microemulsion drug delivery system (SMEDDS) is always applied to enhance the solubility of hydrophobic and lipophilic drugs. In recent years, the technology has been used for the development and study of insoluble drugs. However, the specific absorption mechanism of SMEDDS in vivo has not been clearly illustrated. In this study, we prepared oridonin self-microemulsion drug delivery systems (ORI-SMEDDS) with different charges. For instance, ORI-SMEDDS with positive zeta potential is marked as + SMEDDS, ORI-SMEDDS with negative zeta potential is marked as − SMEDDS. The formulations were then subjected to in vitro lipolysis, in vitro permeation, and single-pass intestinal perfusion studies. The results of these experiments showed that drug absorption and permeation in the small intestine could be affected by the composition of oil phase of ORI-SMEDDS and the presence of fasting. Particularly, we noticed that the net charge carried by ORI-SMEDDS significantly affect the absorption and uptake of ORI in the small intestine. In the pharmacokinetic studies, ORI-SMEDDS prolonged the retention of the ORI in vivo. Comparing with the suspensions, +SMEDDS and -SMEDDS presented relative bioavailability of 169.65% and 193.34%, respectively. In conclusion, our study confirmed that oil phase composition of the SMEDDS, surface charge, and the specific absorption site in the intestine are several factors that have impacts on the absorption and permeation of SMEDDS in the intestinal. Predominantly, the charging condition of SMEDDS is the main factor affecting the absorption process in vivo. ORI-SMEDDS, as an alternative and promising drug delivery system for oridonin, showed a bright future in its broad clinical application.

How to achieve efficient drug accumulation in the tumor with low vascular density is a great challenge but the key to push the limit of anti-vascular therapeutic efficacy. Herein, we report a charge-reversible nanoparticles of gambogenic acid (CRNP-GNA) that would induce the positive feedback loop between increased tumor vascular permeability and improved drug accumulation. This positive feedback loop would remarkably improve tumor vascular permeability for efficient drug accumulation through few residue vessels. As compared to its charge-irreversible analogue in the latter injections, the accumulation in tumor and vascular permeability and retention indexes (VPRI) in CRNP-GNA group respectively boosted from nearly equal to 8.32 and 60 times, while its tumorous microvessel density decreased from nearly equal to only 7%. The self-augmented accumulation consequently amplified the antitumor efficacy via multiple pathways of anti-angiogenesis, vascular disruption and pro-apoptosis, where 5 out of 6 tumors in animal models were completely cured by CRNP-GNA. This work confirms that the underlying positive feedback loop for anti-vascular therapy could be induced by charge-reversible drug delivery nanosystem to achieve efficient and self-augmented drug accumulation even in the tumor with few vessels. It provides a novel strategy to conquer the dilemma between anti-vascular efficacy and drug accumulation.

In this study, alkali-soluble polysaccharide was extracted from Poria residue, and the structure of alkali-soluble polysaccharide was characterized by Fourier transform infrared spectroscopy（FTIR）, X-ray powder diffraction（XRD）, and differential scanning calorimetry（DSC）. The physical morphology of alkali-soluble polysaccharide and ethyl cellulose（EC） was investigated by scanning electron microscopy（SEM）, and the focus on angle of repose, bulk density, tapped density, Carr index, interparticle porosity, cohesion index, Hausner ratio,etc. The physical fingerprints were drawn, and the powder properties were evaluated by multivariate analysis.Diclofenac sodium extended-release tablets were prepared by direct compression method using alkali-soluble polysaccharide and EC as insoluble backbone materials to evaluate the basic properties of the extended-release tablets, investigate the in vitro drug release behavior and study the release mechanism. The results showed that alkali-soluble polysaccharide is a semi-crystalline polymer with smooth lamellar structure, and its stacking and compressibility are stronger than EC. The in vitro release experiments showed that the slow release performance of alkali-soluble polysaccharide is stronger than EC, and the release behavior of the prepared slow release tablets is in accordance with the Higuchi model. The pore structure is formed inside the tablets during the release process, and the release mode is pore diffusion release. The results of this study are of great significance for the development of new slow-release materials and the rational use of resources.

Gegen Qinlian Decoction, derived from Zhang Zhongjing's Treatise on Typhoid Fever, has been widely used in the treatment of various common diseases, frequently-occurring diseases and difficult and complicated diseases, such as ulcerative colitis. In this study, Bletilla striata polysaccharide (BSP) was innovatively used as a film coating material to prepare Gegen Qinlian pellets with dual sensitivity of pH enzyme for the treatment of ulcerative colitis. BSP has the ability to repair the inflamed colon mucosa and can produce synergistic effects, while avoiding the adverse therapeutic effects caused by the early release of drugs from a single pH-sensitive pellets in the small intestine. The prepared pellets have a uniform particle size, good roundness, a particle size range from 0.8 mm to 1.0 mm, and a particle yield is 85.6 %. The results of in vitro release showed that ES-BSP pellets hardly released drugs in the pH range of 1.2-6.8. However, in the colon mimic fluid containing specific enzymes, the drug release was significantly accelerated, demonstrating the sensitivity of the pellets to pH enzymes. In vivo and ex vivo fluorescence imaging of small animals showed that Gegen Qinlian pellets with dual sensitivity of pH enzyme remained longer in the colon compared with pH-sensitive pellets. In vivo pharmacodynamics study showed that the Gegen Qinlian pellets with dual sensitivity of pH enzyme had a better therapeutic effect in the rat model of the ulcerative colon than the commercially available Gegenqinlian pellets in the control group.