Search Results (162)

Background/Objectives: Ulcerative colitis (UC) involves chronic colon inflammation and oxidative stress. Treating UC is challenging due to systemic drug side effects and poor targeted delivery. Nanocarriers responsive to the UC microenvironment, particularly elevated reactive oxygen species (ROS), could overcome these limitations. This study developed an oral delivery system for ROS-triggered drug release and active targeting. Using ferulic acid (FER), a system was designed to enhance site-specific accumulation and therapeutic efficacy against colitis. Methods: A ROS-sensitive covalent organic framework (COF) was synthesized from γ-cyclodextrin and functionalized with folic acid (FA) to create a carrier (COF-FA) designed for potential active targeting. This carrier was loaded with FER to form FER@COF-FA. The system was characterized (SEM, FTIR, TGA), and its ROS scavenging and sustained drug release profiles were confirmed in vitro. Biocompatibility was evaluated in cell lines, and therapeutic efficacy was tested in a DSS-induced murine colitis model. Results: The synthesized FER@COF-FA demonstrated high drug loading, potent ROS-scavenging capability, and a sustained drug release profile. It showed excellent biocompatibility and, in the murine model, significantly outperformed free FER. Treatment alleviated disease severity, prevented colon shortening, restored healthy tissue histology, and rebalanced pro- and anti-inflammatory cytokines. Conclusions: The FER@COF-FA system represents a highly promising therapeutic strategy for UC. Its superior efficacy is attributed to a synergistic multi-mechanism approach, combining sustained release, ROS-responsive drug delivery, intrinsic antioxidant activity, and potential folate receptor-mediated targeting, which collectively enhance site-specific accumulation and therapeutic outcomes in the inflammatory colon microenvironment. Full article

Curcumin (CUR) is a bioactive compound with well-documented therapeutic potential in diverse pathological conditions, encompassing intestinal disorders—most notably colonic cancer—as well as extra-intestinal malignancies such as hepatic, breast, and renal tumors. However, the therapeutic efficacy of CUR is severely constrained by its poor aqueous solubility, chemical instability, and consequent low systemic bioavailability. Nano-scaled carriers (nanocurcumin) enhance CUR solubility and membrane permeability through their reduced dimensions and/or specific interactions with membrane constituents. Nevertheless, conventional nanocurcumin formulations, such as unmodified liposomes, nanocapsules, nanogels, and nanofibers, continue to accumulate substantially in non-target tissues because of their lack of disease-specific tropism. This review focuses on the most recent advances in active targeting strategies for nanocurcumin, specifically receptor-mediated cellular targeting for extra-intestinal pathologies and colon-specific ligand-directed delivery for intestinal disorders. Current methodologies for validating the efficacy of engineered nanocurcumin formulations are critically reviewed, and the prevailing limitations alongside prospective future applications of nanocurcumin are delineated and discussed. Full article

Carbon nanotubes have shown great promise in drug delivery systems as they can easily penetrate the cell membrane. Herein, carbon nanotubes functionalized with polyethylene glycol and folic acid were used to improve target specificity in breast and colon cancer cells. The functionalized carbon nanotubes were bioconjugated with bioactive compounds from plant extracts. In vitro cytotoxicity studies were conducted to demonstrate cellular uptake and apoptosis due to bioconjugate cellular internalization. The bioconjugates were able to preserve normal cells and induce cell death in cancer cells. The efficacy of the carbon nanotube bioconjugates in this study shows great potential in cancer therapy applications. Full article

In recent years, the global prevalence of pediatric allergic diseases—including atopic dermatitis, allergic rhinitis, and asthma—has increased significantly. Accumulating evidence underscores the pivotal role of the microbiota–immune axis in the regulation of immune tolerance, wherein microbial dysbiosis is a critical driver in the onset and progression of these conditions. Notably, reduced microbial diversity and imbalanced proportions can also cause immune dysregulation and cross-organ signaling. The skin–lung–gut axis has emerged as a key conduit for multi-organ immune communication. Microbial communities at barrier sites not only mediate local immune homeostasis but also influence distant organs through metabolite production and immune signaling pathways, forming a complex network of organ crosstalk. This mechanism is integral to the maintenance of both innate (e.g., epithelial barrier integrity and phagocytic activity) and adaptive (e.g., the Type 1/Type 2 cytokine balance and regulatory T cell function) immunity, thereby suppressing allergic inflammation. Early microbial colonization is crucial for immune system maturation, and its perturbation is strongly linked to abnormal allergic immune responses. As such, the skin–lung–gut axis functions as a cross-organ microecological–immune regulatory network that is particularly relevant in the context of infantile allergic disorders. Intervention strategies targeting the microbiota—including probiotics, prebiotics, synbiotics, and postbiotics—have demonstrated potential in modulating host immunity. Furthermore, emerging approaches such as engineered probiotics, advanced delivery systems, and fecal microbiota transplantation (FMT) offer promising therapeutic avenues. This review provides a comprehensive overview of microbiota development in early life, its association with allergic disease pathogenesis, and the current progress in microbiota-targeted interventions, offering a theoretical foundation for individualized prevention and treatment strategies. Full article

Colon cancer ranks among the most prevalent and lethal cancers worldwide. Lifestyle and dietary factors—such as high consumption of processed foods, red meat, and alcohol, coupled with sedentary behavior—are key contributors to its development. Despite the availability of standard treatments like surgery, chemotherapy, and radiotherapy, colon cancer remains a significant cause of cancer-related deaths. These conventional approaches are often limited by severe side effects, toxicity, recurrence, and the emergence of drug resistance, highlighting the urgent need for alternative therapeutic strategies. Essential oils are a potential cancer-treatment candidate owing to their diverse composition and favorable safety profile. Numerous studies have revealed essential oils’ promising cytotoxic, antioxidant, and anti-inflammatory effects, supporting their potential role in cancer prevention and treatment. Nevertheless, applying volatile oils to the colon faces several limitations, mainly due to their low bioavailability. Furthermore, conditions within the gastrointestinal tract also contribute to the reduced therapeutic efficacy of essential oils. Novel and promising strategies have been developed to overcome the limitations associated with the application of essential oils. The utilization of targeted drug delivery systems has improved the stability of essential oils and enhanced their therapeutic potential in colon cancer treatment. Moreover, even though essential oils cannot replace conventional chemotherapy, they can mitigate some of its adverse effects and improve the efficacy of associated chemotherapy drugs. This review explores the potential of essential oils and their bioactive compounds in colon cancer therapy and highlights current advancements in micro- and nanoencapsulation techniques for their targeted delivery to the colon. Full article

In recent years, combination chemotherapy with therapeutic nucleic acids has emerged as a promising strategy to enhance the effectiveness of cancer therapy. However, developing an effective co-delivery system to simultaneously transport both chemotherapeutic drugs and nucleic acids remains challenging. Herein, we fabricated cholesterol-conjugated polyion complex nanoparticles (PCNs) for combination delivery of hydrophobic paclitaxel (PTX) and hydrophilic miR-34a. Cholesterol was conjugated to polyethylenimine (PEI) and hyaluronic acid (HA), producing C–PEI and C–HA, respectively. PTX was initially encapsulated within the hydrophobic core formed by the self-assembly of C–HA and C–PEI, yielding polyion complex nanoparticles (PTX@C–HA/C–PEI PCNs). Subsequently, the negatively charged miR-34a was electrostatically complexed with the cationic C–PEI moieties to generate miR-34a/PTX@C–HA/C–PEI PCNs. These PCNs exhibited a nanoscale structure with a uniform size distribution and demonstrated low cytotoxicity in colon cancer cells. Fluorescence microscopy confirmed efficient cytosolic delivery of C–HA/C–PEI PCNs in colon carcinoma cells. Furthermore, combination delivery of PTX and miR-34a using C–HA/C–PEI PCNs exhibited significantly enhanced transfection efficiency and cellular uptake for human colon cancer cells. Notably, PTX/miR-34a@C–HA/C–PEI PCNs effectively downregulated critical oncogenic targets, including Notch1, Snail1, and BCL-2, resulting in reduced cancer cell migration and proliferation. These findings indicate that PTX/miR-34a@C–HA/C–PEI PCNs hold significant potential as an innovative combination delivery platform, offering improved therapeutic efficacy for colon cancer therapy. Full article

Resistant starch (RS) is emerging as a multifunctional dietary component and delivery platform for microbiota-accessible carbohydrates. Upon fermentation by gut microbiota, particularly in the colon, RS generates a wide spectrum of postbiotic compounds—including short-chain fatty acids (SCFAs), indoles, bile acid derivatives, and neuroactive amines such as GABA and serotonin precursors. These metabolites modulate gut–brain signaling, immune responses, and intestinal barrier integrity, which are critical pathways in the pathophysiology of irritable bowel syndrome (IBS). This review synthesizes current knowledge on RS structure, classification, and fermentation dynamics, with a special focus on RS3 due to its practical dietary relevance and strong microbiota-modulatory effects. We highlight emerging evidence from clinical studies supporting RS-mediated improvements in IBS symptoms, microbial diversity, and inflammation. Importantly, RS acts as a smart colonic delivery system by escaping enzymatic digestion in the small intestine and reaching the colon intact, where it serves as a targeted substrate for microbial fermentation into bioactive metabolites. This host–microbiota interplay underpins the development of personalized, microbiome-informed nutrition interventions tailored to specific IBS subtypes. Future directions include omics-based stratification, optimized RS formulations, and predictive algorithms for individualized responses. This review aims to clarify the mechanistic links between RS fermentation and postbiotic production, highlighting its therapeutic potential in IBS management. Full article

Notoginsenoside Rb1 (Rb1), a bioactive saponin from Panax notoginseng, exerts cardio-cerebrovascular protective, anti-inflammatory, antioxidant, and glucose homeostasis-regulating effects. However, its oral bioavailability is limited by gastric degradation and poor intestinal permeability. This study presents a food-grade bigel system for encapsulating Rb1 to enhance its stability and controlled-release performance. Oleogels were structured using monoglycerides (8%, w/w) in soybean oil. Rb1-loaded binary hydrogels (gellan gum/xanthan gum, 12:1 w/w) were emulsified in 10% Tween-80 (w/w). Bigels were formulated at varying hydrogel-to-oleogel ratios, and a ratio of 4:6 was identified as optimal. Stress-sweep rheological analysis revealed a dense gel structure with a peak storage modulus (G′) of 290.64 Pa—the highest among all tested ratios—indicating superior structural integrity. Confocal microscopy confirmed homogeneous encapsulation of Rb1 within the continuous hydrogel phase, effectively preventing payload leakage. Differential scanning calorimetry (DSC) analysis detected a distinct endothermic transition at 55 °C (ΔH = 6.25 J/g), signifying energy absorption that enables thermal buffering during food processing. The system achieved an encapsulation efficiency of 99.91% and retains both water and oil retention. Effective acid protection and colon-targeted delivery were observed in the digestion test. Effective acid protection and colon-targeted delivery were observed in the digestion test. Less than 5% of Rb1 was released in the gastric phase, and over 90% sustained intestinal release occurred at 4 h. The optimized bigel effectively protected Rb1 from gastric degradation and enabled sustained intestinal release. Its food-grade composition, thermal stability, and tunable rheology offer significant potential for use in functional foods and nutraceuticals. Full article

Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, driven by chronic inflammation, gut microbiota dysbiosis, and complex tumor microenvironment interactions. Current therapies are limited by systemic toxicity and poor tumor accumulation. This study aimed to develop a ROS/enzyme dual-responsive oral drug delivery system, KGM-CUR/PSM microspheres, to achieve precise drug release in CRC and enhance tumor-specific drug accumulation, which leverages high ROS levels in CRC and the β-mannanase overexpression in colorectal tissues. Methods: In this study, we synthesized a ROS-responsive prodrug polymer (PSM) by conjugating polyethylene glycol monomethyl ether (mPEG) and mesalazine (MSL) via a thioether bond. CUR was then encapsulated into PSM using thin-film hydration to form tumor microenvironment-responsive micelles (CUR/PSM). Subsequently, konjac glucomannan (KGM) was employed to fabricate KGM-CUR/PSM microspheres, enabling targeted delivery for colorectal cancer therapy. The ROS/enzyme dual-response properties were confirmed through in vitro drug release studies. Cytotoxicity, cellular uptake, and cell migration were assessed in SW480 cells. In vivo efficacy was evaluated in AOM/DSS-induced CRC mice, monitoring tumor growth, inflammatory markers (TNF-α, IL-1β, IL-6, MPO), and gut microbiota composition. Results: In vitro drug release studies demonstrated that KGM-CUR/PSM microspheres exhibited ROS/enzyme-responsive release profiles. CUR/PSM micelles demonstrated significant anti-CRC efficacy in cytotoxicity assays, cellular uptake studies, and cell migration assays. In AOM/DSS-induced CRC mice, KGM-CUR/PSM microspheres significantly improved survival and inhibited CRC tumor growth, and effectively reduced the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and myeloperoxidase (MPO). Histopathological and microbiological analyses revealed near-normal colon architecture and microbial diversity in the KGM-CUR/PSM group, confirming the system’s ability to disrupt the “inflammation-microbiota-tumor” axis. Conclusions: The KGM-CUR/PSM microspheres demonstrated a synergistic enhancement of anti-tumor efficacy by inducing apoptosis, alleviating inflammation, and modulating the intestinal microbiota, which offers a promising stimuli-responsive drug delivery system for future clinical treatment of CRC. Full article

Background/Objectives: 5-Fluorouracil (5-FU) and Irinotecan (IRT) are two of the most used chemotherapeutic agents in CRC treatment. However, achieving treatment goals has been hampered by poor drug delivery to tumor sites and associated toxicity from off-target binding to healthy cells. Though the synergism of 5-FU-IRT has provided incremental improvements in clinical outcomes, the short elimination half-life and off-target binding to healthy cells remain significant challenges. We postulated that nanoencapsulation of a combination of 5-FU and IRT in niosomes would prolong the drugs’ half-lives, while over-encapsulation lyophilized powder in Targit^® oral capsules would passively the CRC microenvironment and avoid extensive systemic distribution. Methods: Ranges of formulation and process variables were input into design of experiment (DOE Fusion One) software, to generate screening experiments. Niosomes were prepared using the thin-film hydration method and characterized by size, the polydispersity index (PDI), morphology and intrastructure, and drug loading. Blank niosomes ranged in size from 215 nm to 257 nm. Results: After loading with the 5-FU-IRT combination, the niosomes averaged 251 ± 2.20 nm with a mean PDI of 0.293 ± 0.01. The surfactant-to-cholesterol ratio significantly influenced the niosome size and the PDI. The hydrophilic 5-FU exhibited superior loading compared to the lipophilic IRT molecules, which probably competed with other lipophilic niosome components in niosomes’ palisade layers. In vitro dissolution in biorelevant media showed delayed release until lower intestinal region (IRT) or colonic region (5-FU). Conclusions: Thus, co-nanoencapsulation of 5-FU/IRT in niosomes, lyophilization, and over-encapsulation of powder in colon-specific capsules could passively target the CRC cells in the colonic microenvironment. Full article

Background/Objectives: This study aimed to enhance the oral delivery and therapeutic synergy of atorvastatin (AT) and docetaxel (DT) through a metronomic schedule using a transporter-targeted nanoemulsion (NE), with the goal of improving antitumor efficacy and immune modulation. Methods: AT and DT were co-encapsulated in a NE system (AT/DT-NE#E) incorporating deoxycholic acid–DOTAP (D-TAP), biotin-conjugated phospholipid (Biotin-PE), and d-α-tocopherol polyethylene glycol succinate (TPGS) to exploit bile acid and multivitamin transport pathways and inhibit P-glycoprotein efflux. The optimized NE was characterized physicochemically and evaluated for permeability in artificial membranes and Caco-2/HT29-MTX-E12 monolayers. Pharmacokinetics, tumor suppression, and immune cell infiltration were assessed in vivo using rat and CT26.CL25 mouse models. Results: AT/DT-NE#E showed enhanced permeability of AT and DT by 45.7- and 43.1-fold, respectively, across intestinal cell models and improved oral bioavailability by 118% and 376% compared to free drugs. In vivo, oral metronomic AT/DT-NE#E reduced tumor volume by 65.2%, outperforming intravenous AT/DT. Combination with anti-PD1 therapy achieved a 942% increase in tumor suppression over the control, accompanied by marked increases in tumor-infiltrating CD45⁺, CD4⁺CD3⁺, and CD8⁺CD3⁺ T cells. Conclusions: Oral metronomic administration of AT/DT via a dual-transporter-targeted NE significantly improves drug absorption, tumor inhibition, and immune response. This strategy presents a safe and effective approach for colon cancer therapy, particularly when combined with immunotherapy. Full article

Ferulic acid (FA) exhibits beneficial properties in ulcerative colitis (UC) pathogenesis, while sensitivity to the environment and enzymes limits its use in UC therapy. Therefore, this study aims to develop a colon-targeted nanocomplex delivery system using FA and investigate its protective effects and underlying regulatory mechanisms in UC mice. A novel Zein/FA–pectin (PEC)/chitosan (CS) nanocomplex was successfully fabricated in this study. Through systematic adjustment of the PEC/CS-to-Zein/FA ratio, optimal encapsulation efficiency (60.1%) and loading capacity (26.2%) were achieved. The characterized data indicated that hydrogen bonds, electrostatic interactions, and hydrophobic forces were the main driving forces maintaining the formation of the nanocomplexes, accompanied by alterations in the secondary structure of Zein. The Zein/FA–PEC/CS nanocomplexes demonstrated excellent thermal/storage particle size stability and exhibited both protective and sustained-release effects of FA during simulated gastrointestinal digestion. Furthermore, the results demonstrated that the nanocomplexes potentially alleviate UC by regulating inflammatory cytokines, oxidative stress, and gut microbiota. Compared to unencapsulated FA, the nanocomplexes have a better effect on alleviating UC symptoms. In summary, Zein/FA–PEC/CS nanocomplexes have promising prospects in alleviating colitis in UC mice. Full article

Probiotics, as live microbial agents, play a pivotal role in modulating host microbiota balance, enhancing immunity, and improving gastrointestinal health. However, their application is hindered by critical challenges, such as inactivation during processing, storage, and gastrointestinal delivery, as well as low colonization efficiency. This article comprehensively reviews recent advances in probiotic delivery systems, focusing on innovative technologies, including hydrogels, nanocoatings, emulsions, and core–shell microgels. It provides an in-depth analysis of natural polyphenol-based nanocoatings and metal–phenolic network (MPN) single-cell encapsulation strategies for enhancing bacterial survival rates while highlighting the unique potential of microalgae-based bio-carriers in targeted delivery. Research demonstrates that well-designed edible delivery systems can effectively preserve probiotic viability and enable controlled intestinal release, offering novel strategies to reshape a healthy gut microbiome. While these systems show promise in maintaining probiotic activity and gut colonization, challenges remain in safety, scalable production, and clinical translation. Overcoming these barriers is crucial to fully harnessing probiotics for human health. Full article

Background:Salmonella Typhimurium is a major zoonotic pathogen, in which type 1 fimbriae play a crucial role in intestinal colonization and immune modulation. This study aimed to improve the protective immunity of a previously developed growth-deficient strain—a double auxotroph for D-glutamate and D-alanine—by engineering the inducible expression of type 1 fimbriae. Methods: P_tetA-driven expression of the fim operon was achieved by λ-Red mutagenesis. fimA expression was quantified by qRT-PCR, and fimbriation visualized by transmission electron microscopy. Adhesive properties were evaluated through FimH sequence analysis, yeast agglutination, mannose-binding/inhibition assays, and HT-29 cell adherence. BALB/c mice were immunized orogastrically with IRTA ΔΔΔ or IRTA ΔΔΔ P_tetA::fim. Safety and immunogenicity were assessed by clinical monitoring, bacterial load, fecal shedding, ELISA tests, and adhesion/blocking assays using fecal extracts. Protection was evaluated after challenging with wild-type and heterologous strains. Results: IRTA ΔΔΔ P_tetA::fim showed robust fimA expression, dense fimbrial coverage, a marked mannose-sensitive adhesive phenotype and enhanced HT-29 attachment. Fimbrial overexpression did not alter intestinal colonization or translocation to mesenteric lymph nodes (mLNs). Immunization elicited a mixed IgG1/IgG2a, significantly increased IgA and IgG against type 1 fimbriae-expressing Salmonella, and enhanced the ability of fecal extracts to inhibit the adherence of wild-type strains. Upon challenge (IRTA wild-type/20220258), IRTA ΔΔΔ P_tetA::fim reduced infection burden in the cecum (−1.46/1.47-log), large intestine (−1.35/2.17-log), mLNs (−1.32/0.98-log) and systemic organs more effectively than IRTA ΔΔΔ. Conclusions: Inducible expression of type 1 fimbriae enhances mucosal immunity and protection, supporting their inclusion in next-generation Salmonella vaccines. Future work should assess cross-protection and optimize FimH-mediated targeting for mucosal delivery. Full article

Probiotics are widely used as dietary additives to strengthen gut barrier function, shape microbiota composition, regulate host metabolism, and promote overall health. To enhance probiotic delivery and microbial viability, this study evaluated a liquid feeding system supplemented with a probiotic consortium (Bifidobacterium infantis, Lactobacillus plantarum, and Pediococcus acidilactici) in nursery piglets. A 60-day trial involving 270 piglets (16.84 ± 0.12 kg) compared three diets: solid feed (Dry), liquid feed (Liq), and probiotic-enriched liquid feed (Pro). Compared to the Dry and Liq groups, probiotic supplementation significantly improved growth performance, with the average daily gain increasing by over 17.86% (p < 0.01) and the average daily feed intake increasing by more than 6.08% (p < 0.05). The feed conversion ratio was reduced by up to 8.08% (p < 0.05), indicating improved feed efficiency. The Pro group also exhibited elevated tight junction protein expression (p < 0.05), increased colonic short-chain fatty acid levels (p < 0.01), and decreased serum biomarkers of intestinal permeability (p < 0.05). The 16 S rRNA sequencing indicated the probiotic-driven colonization of B. infantis and L. plantarum and the suppression of opportunistic pathogens. Metabolomic analyses revealed enhanced colonic tryptophan metabolism, evidenced by elevated kynurenic and xanthurenic acid levels. Additionally, serum-targeted metabolomics and in vitro experiments confirmed that B. infantis and L. plantarum effectively converted tryptophan into indole-3-lactic acid, promoting its accumulation in piglet serum and colons. These results deepen our understanding of the mechanisms by which probiotics and tryptophan metabolism enhance intestinal health, providing a foundational platform for the application of probiotic-based interventions in livestock production. Full article