Inflammatory Bowel Disease Therapy Research Articles

Bioorthogonal conjugation and responsive nanocoating of probiotics for inflammatory bowel disease

Inflammatory bowel disease (IBD) is closely associated with dysregulated immune response, gut mucosal barrier, and microbiota. Conventional treatments suffer from inferior bioavailability and inadequate efficiency. Herein, we present a synergistic therapeutic strategy based on multifunctionalized probiotics to mitigate IBD through single oral administration. The probiotic (Escherichia coli Nissle 1917) is bioorthogonally conjugated with immunomodulators and subsequently encapsulated by an enteric coating. The viability and bioactivity of probiotics are not affected by the modifications. And the armored probiotics are able to resist the harsh environment of the stomach and shed their enteric coating in the intestinal tract, exposing immunomodulators to polarize pro-inflammatory M1-type macrophages into anti-inflammatory M2-type. In a mouse colitis model, orally administered multifunctionalized probiotics cooperatively alleviate IBD with increased body weight to 1.13 folds and decreased disease activity index to 0.43 folds, through downregulating the pro-inflammatory cytokines expression, upregulating the epithelial tight junction-associated proteins levels to restore the intestinal barrier, and increasing the microbiota richness and abundance. This work exhibits a feasible approach to construct functionalized orally administered probiotics for enhanced synergistic therapy of IBD.

Combined Advanced Targeted Therapy in Inflammatory Bowel Diseases: An Extensive Update.

Combined Advanced Targeted Therapy in Inflammatory Bowel Diseases: An Extensive Update.

Zein: Potential biopolymer in inflammatory bowel diseases.

Effectively managing inflammatory bowel disease (IBD) poses difficulties due to its persistent nature and unpredictable episodes of exacerbation. There is encouraging evidence that personalized medication delivery systems can improve therapy efficacy while reducing the negative effects of standard medicines. Zein, a protein produced from corn, has garnered interest as a possible means of delivering drugs for the treatment of IBD. This review delves into Zein-based drug delivery systems, showcasing its biodegradability, controlled release capabilities, and biocompatibility. Studies have shown that Zein-based nanoparticles, microcarriers, and core-shell microparticles have the capacity to increase medication stability, enhance targeting in the intestines, and decrease toxicity in animal models of IBD. The review highlights the promise of Zein in personalized therapy for IBD and urges more study to enhance its clinical use.

Bioinspired micro-nano hierarchical delivery system for sequential targeted therapy of inflammatory bowel disease

Inflammatory bowel disease (IBD) constitutes an immense health and economic burden worldwide, highlighting the need for improved therapy. Up to now, various delivery systems have been proposed to enhance IBD treatment. Herein, inspired by cellular communication in nature, we present a novel micro-nano hierarchical microsphere system with the enhanced targeting capability for IBD treatment. The hierarchical microspheres are designed for oral delivery, with astaxanthin nanoparticles in the core and Zein protein shell. Similar to a stepwise process of cellular communication, microscale spheres can escape from the gastric acid due to Zein coating. Once reach into the intestine, mucoadhesive Zein coating and the core could be enzymatically digested, following the targeted release of astaxanthin nanoparticles. Particularly, these astaxanthin nanoparticles are endowed with the mitochondria targeting capability, thereby greatly attenuating pro-inflammatory response of macrophages. Based on these features, practical performances of the hierarchical delivery system have been investigated in both acute and chronic colitis model. Animal experiments have revealed the desired therapeutic effects of the hierarchical microspheres by inhibiting inflammatory responses and modulating gut microbiota. These results suggested the present hierarchical delivery system offers a stepwise strategy for nanodrug delivery to the intestine as well as the effective treatment of IBD.

Natural medicines-derived carbon dots as novel oral antioxidant administration strategy for ulcerative colitis therapy

BackgroundUlcerative colitis (UC) is a chronic intestinal inflammation, resulting in a global healthcare challenge with no real specific medicine. Natural medicines are recognized as a potential clinical alternative therapy, but their applications are limited by poor solubility and low bioavailability.ResultsIn this work, inspired by the natural medicines of ancient China, novel functional carbon dots derived from Magnetite and Medicated Leaven (MML-CDs) were synthesized by hydrothermal method, and confirmed their ultrasmall nano-size (3.2 ± 0.6 nm) and Fe doped surface structure, thereby with excellent gastrointestinal stability, remarkable capabilities in eliminating ROS, and highly biocompatibility. With no external stimuli, the oral administration of MML-CDs demonstrated obvious alleviation to UC. Further experiments pointed that MML-CDs could improve hemostasis capability, suppress inflammation reactions and oxidative stress, and up-regulate the expression of tight junction proteins. Furthermore, MML-CDs also showed well regulation in the dysbiosis of intestinal flora.ConclusionOverall, above evidence reveals that green-synthesized MML-CDs can significantly alleviate intestinal bleeding, inhibit colon inflammation, and repair colonic barrier damage, further regulating intestinal flora and intestinal inflammation microenvironment. Our findings provide an efficient oral administration of MML-CDs as a novel therapy strategy for ulcerative colitis.Graphical

Dynamic changes in the gut microbiota composition during adalimumab therapy in patients with ulcerative colitis: implications for treatment response prediction and therapeutic targets

BackgroundWhile significant research exists on gut microbiota changes after anti-tumor necrosis factor-alpha (anti TNF-α) therapy for ulcerative colitis, little is known about the longitudinal changes related to the effects of anti TNF-α. This study aimed to investigate the dynamics of gut microbiome changes during anti TNF-α (adalimumab) therapy in patients with ulcerative colitis (UC).ResultsThe microbiota composition was affected by the disease severity and extent in patients with UC. Regardless of clinical remission status at each time point, patients with UC exhibited microbial community distinctions from healthy controls. Distinct amplicon sequence variants (ASVs) differences were identified throughout the course of Adalimumab (ADA) treatment at each time point. A notable reduction in gut microbiome dissimilarity was observed only in remitters. Remitters demonstrated a decrease in the relative abundances of Burkholderia-Caballeronia-Paraburkholderia and Staphylococcus as the treatment progressed. Additionally, there was an observed increase in the relative abundances of Bifidobacterium and Dorea. Given the distribution of the 48 ASVs with high or low relative abundances in the pre-treatment samples according to clinical remission at week 8, a clinical remission at week 8 with a sensitivity and specificity of 72.4% and 84.3%, respectively, was predicted on the receiver operating characteristic curve (area under the curve, 0.851).ConclusionsThe gut microbiota undergoes diverse changes according to the treatment response during ADA treatment. These changes provide insights into predicting treatment responses to ADA and offer new therapeutic targets for UC.

Limited predictive value of the gut microbiome and metabolome for response to biological therapy in inflammatory bowel disease

ABSTRACT Emerging evidence suggests the gut microbiome’s potential in predicting response to biologic treatments in patients with inflammatory bowel disease (IBD). In this prospective study, we aimed to predict treatment response to vedolizumab and ustekinumab, integrating clinical data, gut microbiome profiles based on metagenomic sequencing, and untargeted fecal metabolomics. We aimed to identify predictive biomarkers and attempted to replicate microbiome-based signals from previous studies. We found that the predictive utility of the gut microbiome and fecal metabolites for treatment response was marginal compared to clinical features alone. Testing our identified microbial ratios in an external cohort reinforced the lack of predictive power of the microbiome. Additionally, we could not confirm previously published predictive signals observed in similar sized cohorts. Overall, these findings highlight the importance of external validation and larger sample sizes, to better understand the microbiome’s impact on therapy outcomes in the setting of biologicals in IBD before potential clinical implementation.

Current Treatments, Emerging Therapeutics, and Natural Remedies for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic, lifelong disorder characterized by inflammation of the gastrointestinal (GI) tract. The exact etiology of IBD remains incompletely understood due to its multifaceted nature, which includes genetic predisposition, environmental factors, and host immune response dysfunction. Currently, there is no cure for IBD. This review discusses the available treatment options and the challenges they present. Importantly, we examine emerging therapeutics, such as biologics and immunomodulators, that offer targeted treatment strategies for IBD. While many IBD patients do not respond adequately to most biologics, recent clinical trials combining biologics with small-molecule drugs (SMDs) have provided new insights into improving the IBD treatment landscape. Furthermore, numerous novel and specific therapeutic targets have been identified. The high cost of IBD drugs poses a significant barrier to treatment, but this challenge may be alleviated with the development of more affordable biosimilars. Additionally, emerging point-of-care protein biomarkers from serum and plasma are showing potential for enhancing the precision of IBD diagnosis and prognosis. Several natural products (NPs), including crude extracts, small molecules, and peptides, have demonstrated promising anti-inflammatory activity in high-throughput screening (HTS) systems and advanced artificial intelligence (AI)-assisted platforms, such as molecular docking and ADMET prediction. These platforms are advancing the search for alternative IBD therapies derived from natural sources, potentially leading to more affordable and safer treatment options with fewer side effects.

Oral delivery of sodium alginate/chitosan bilayer microgels loaded with Lactobacillus rhamnosus GG for targeted therapy of ulcerative colitis

Probiotics regulate intestinal flora balance and enhance the intestinal barrier, which is useful in preventing and treating colitis. However, they have strict storage requirements. In addition, they degrade in a strongly acidic environment, resulting in a significant decrease in their activity when used as microbial agents. Lactobacillus rhamnosus GG (LGG) was loaded into acid-resistant and colon-targeting double-layer microgels. The inner layer consists of guar gum (GG) and low methoxyl pectin (LMP), which can achieve retention and degradation in the colon. To achieve colon localization, the outer layer was composed of chitosan (CS) and sodium alginate (SA). The formulation demonstrated favorable bio-responses across various pH conditions in vitro and sustained release of LGG in the colon lesions. Bare LGG survival decreased by 52.2 % in simulated gastric juice (pH 1.2) for 2 h, whereas that of encapsulated LGG decreased by 18.5 %. In the DSS-induced inflammatory model, LGG-loaded microgel significantly alleviated UC symptoms in mice and reduced inflammatory factor levels in the colon. Encapsulation of LGG improved its stability in acidic conditions, thus increasing its content at the colon lesions and reducing pathogenic bacteria. These findings provide an experimental basis and a technical reference for developing and applying probiotic microgel preparations.

Role of Extracellular Vesicles in Crohn's Patients on Adalimumab Who Received COVID-19 Vaccination.

Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) affecting the gastrointestinal tract that can also cause extra-intestinal complications. Following exposure to the mRNA vaccine BNT162b2 (Pfizer-BioNTech) encoding the SARS-CoV-2 Spike (S) protein, some patients experienced a lack of response to the biological drug Adalimumab and a recrudescence of the disease. In CD patients in progression, resistant to considered biological therapy, an abnormal increase in intestinal permeability was observed, more often with a modulated expression of different proteins such as Aquaporin 8 (AQP8) and in tight junctions (e.g., ZO-1, Claudin1, Claudin2, Occludin), especially during disease flares. The aim of this study is to investigate how the SARS-CoV-2 vaccine could interfere with IBD therapy and contribute to disease exacerbation. We investigated the role of the SARS-CoV-2 Spike protein, transported by extracellular vesicles (EVs), and the impact of various EVs components, namely, exosomes (EXOs) and microvesicles (MVs), in modulating the expression of molecules involved in the exacerbation of CD, which remains unknown.

US National Estimates of Contemporary Mortality Rates in Patients With Ulcerative Colitis Undergoing Colectomy.

Despite a growing armamentarium of medical therapies for ulcerative colitis, colectomy remains an important therapeutic option. To better inform shared decision-making about surgery, we estimated the contemporary risk of mortality after colectomy. Mortality rates were estimated using the National Inpatient Sample (2016-2020). Factors associated with postcolectomy death were evaluated in multivariable regression. Postcolectomy mortality occurred in 1.2% (95% CI: 0.8%, 1.9%) of hospitalizations. Comorbidity burden, emergent laparotomy, and delays to surgery >5 days after admission were associated with mortality. Colectomy may be associated with mortality; however, this risk is heterogeneous based on patient- and procedural-related factors.

Real-World Treatment Persistence Among Advanced Therapy-Naïve or -Experienced Patients with Ulcerative Colitis Initiated on Ustekinumab or Adalimumab.

Persistence on advanced therapies in ulcerative colitis (UC) is a useful real-world treatment performance measure. This study compared real-world persistence during the maintenance phase among advanced therapy-naïve and -experienced patients with UC initiated on ustekinumab or adalimumab. Claims data from the IQVIA PharMetrics® Plus de-identified database (01/01/2015-06/30/2022) were used to select adult patients with UC treated with ustekinumab or adalimumab based on the agent first initiated (index date) after 10/21/2019. Inverse probability of treatment weighting was used to balance cohorts on baseline characteristics. Persistence on the index agent (no gaps in days of supply of>120 days for ustekinumab or>60 days for adalimumab), persistence while corticosteroid-free, while on monotherapy, and persistence on the US labeled dose were described and compared during the 12-month period post-index using Kaplan-Meier analysis and Cox proportional hazards models. Outcomes were analyzed separately among advanced therapy-naïve and advanced therapy-experienced patients. At 12 months post-index, advanced therapy-naïve patients receiving ustekinumab (n=371) had higher persistence on the index agent [83.8% vs. 57.6%, hazard ratio (95% confidence interval) =3.09 (2.29-4.16); p<0.001), persistence while corticosteroid-free [2.00 (1.63-2.45); p<0.001], persistence while on monotherapy [2.67 (2.07-3.44); p<0.001], and persistence on the labeled dose [4.21 (2.76-6.44); p<0.001] versus those receiving adalimumab (n=1726). At 12 months post-index, advanced therapy-experienced patients receiving ustekinumab (n=693) had higher persistence on the index agent [78.1% vs. 59.2%, 2.44 (1.82-3.26); p<0.001], persistence while corticosteroid-free [1.24 (1.01-1.54); p=0.0447], persistence while on monotherapy [2.53 (2.00-3.21); p<0.001], and persistence on the labeled dose [4.77 (3.09-7.35); p<0.001] versus those receiving adalimumab (n=254). This claims-based analysis demonstrated significantly higher treatment persistence, including persistence while corticosteroid-free, persistence while on monotherapy, and persistence on the labeled dose, among both advanced therapy-naïve and advanced therapy-experienced patients with UC initiated on ustekinumab compared to adalimumab.

Yoga in Pediatric Gastroenterology.

Pediatric use of yoga as an integrative medicine modality has increased in prevalence over the last several decades. In this article, we review the available evidence for yoga in pediatric gastrointestinal disorders. Evidence supports that in many pediatric disorders of gut brain interaction (DGBI), including irritable bowel syndrome, functional abdominal pain and functional dyspepsia, yoga decreases pain intensity and frequency and increases school attendance. Yoga has been shown to improve health-related quality of life and improve stress management as an effective adjunct to standard medical therapy in pediatric inflammatory bowel disease (IBD). Further studies are needed regarding optimal frequency, duration of practice and evaluation of the impact on IBD disease activity measures. Yoga may benefit pediatric gastroenterology patients with DGBIs and IBD through improving quality of life and reducing pain. Future yoga studies could investigate biomarkers and continued research will help integrate this modality into routine pediatric gastroenterology care.

Safety and Effectiveness of Thiopurines and Small Molecules in Elderly Patients with Inflammatory Bowel Diseases.

The management of inflammatory bowel diseases (IBD) requires weighing an individual patient's therapeutic benefits and therapy-related complication risks. The immunomodulators that have been commonly used so far in IBD therapy are thiopurines, including 6-mercaptopurine and azathioprine. As our understanding of the IBD pathomechanisms is widening, new therapeutic approaches are being introduced, including the Janus kinase (JAK) inhibitors and Sphingosine 1-phosphate receptor (S1PR) modulators' development. Non-selective JAK inhibitors are represented by tofacitinib, while selective JAK inhibitors comprise filgotinib and upadacitinib. As for the S1PR modulators, ozanimod and etrasimod are approved for UC therapy. The number of elderly patients with IBD is growing; therefore, this review aimed to evaluate the effectiveness and safety of the oral immunomodulators among the subjects aged ≥60. Possible complications limit the use of thiopurines in senior patients. Likewise, the promising effectiveness of new drugs in IBD therapy in those with additional risk factors might be confined by the risk of serious adverse events. However, the data regarding this issue are limited.

A metabolic constraint in the kynurenine pathway drives mucosal inflammation in IBD.

Inflammatory bowel disease (IBD) is associated with perturbed metabolism of the essential amino acid tryptophan (Trp). Whether increased degradation of Trp directly fuels mucosal inflammation or acts as a compensatory attempt to restore cellular energy levels via de-novo nicotinamide adenine dinucleotide (NAD + ) synthesis is not understood. Employing a systems medicine approach on longitudinal IBD therapy intervention cohorts and targeted screening in preclinical IBD models, we discover that steady increases in Trp levels upon therapy success coincide with a rewiring of metabolic processes within the kynurenine pathway (KP). In detail, we identify that Trp catabolism in IBD is metabolically constrained at the level of quinolinate phosphorybosyltransferase (QPRT), leading to accumulation of quinolinic acid (Quin) and a decrease of NAD + . We further demonstrate that Trp degradation along the KP occurs locally in the inflamed intestinal mucosa and critically depends on janus kinase / signal transducers and activators of transcription (JAK/STAT) signalling. Subsequently, knockdown of QPRT in-vitro induces NAD + depletion and a pro-inflammatory state, which can largely be rescued by bypassing QPRT via other NAD + precursors. We hence propose a model of impaired de-novo NAD + synthesis from Trp in IBD. These findings point towards the replenishment of NAD + precursors as a novel therapeutic pathway in IBD.

Matrix metalloproteinase-responsive hydrogels with tunable retention for on-demand therapy of inflammatory bowel disease

Therapeutic options for addressing inflammatory bowel disease (IBD) include the administration of an enema to reduce intestinal inflammation and alleviate associated symptoms. However, uncontrollable retention of enemas in the intestinal tract has posed a long-term challenge for improving their therapeutic efficacy and safety. Herein we have developed a protease-labile hydrogel system as an on-demand enema vehicle with tunable degradation and drug release rates in response to varying matrix metalloproteinase-9 (MMP-9) expression. The system, composed of three tailored hydrogel networks, is crosslinked by poly (ethylene glycol) (PEG) with 2-, 4- and 8-arms through dynamic hydrazone bonds to confer injectability and generate varying network connectivity. The retention time of the hydrogels can be tuned from 12 to 36 h in the intestine due to their different degradation behaviors induced by MMP-9. The drug-releasing rate of the hydrogels can be controlled from 0.0003 mg/h to 0.278 mg/h. In addition, injection of such hydrogels in vivo resulted in significant differences in therapeutic effects including MMP-9 consumption, colon tissue repair, reduced collagen deposition, and decreased macrophage cells, for treating a mouse model of acute colitis. Among them, GP-8/5-ASA exhibits the best performance. This study validates the effectiveness of the tailored design of hydrogel architecture in response to pathological microenvironment cues, representing a promising strategy for on-demand therapy of IBD. Statement of significanceThe uncontrollable retention of enemas at the delivery site poses a long-term challenge for improving therapeutic efficacy in IBD patients. MMP-9 is highly expressed in IBD and correlates with disease severity. Therefore, an MMP-9-responsive GP hydrogel system was developed as an enema by linking multi-armed PEG and gelatin through hydrazone bonds. This forms a dynamic hydrogel characterized by in situ gelation, injectability, enhanced bio-adhesion, biocompatibility, controlled retention time, and regulated drug release. GP hydrogels encapsulating 5-ASA significantly improved the intestinal phenotype of acute IBD and demonstrated notable therapeutic differences with increasing PEG arms. This method represents a promising on-demand IBD therapy strategy and provides insights into treating diseases of varying severities using endogenous stimulus-responsive drug delivery systems.

Recent advances in novel functionalized oral administration therapy for inflammatory bowel diseases

Recent advances in novel functionalized oral administration therapy for inflammatory bowel diseases

Leveraging thiol-functionalized biomucoadhesive hybrid nanoliposome for local therapy of ulcerative colitis

Directly administering medication to inflamed intestinal sites for treating ulcerative colitis (UC), poses significant challenges like retention time, absorption variability, side effects, drug stability, and non-specific delivery. Recent advancements in therapy to treat colitis aim to improve local drug availability that is enema therapy at the site of inflammation, thereby reducing systemic adverse effects. Nevertheless, a key limitation lies in enemas' inability to sustain medication in the colon due to rapid peristaltic movement, diarrhea, and poor local adherence. Therefore, in this work, we have developed site-specific thiolated mucoadhesive anionic nanoliposomes to overcome the limitations of conventional enema therapy. The thiolated delivery system allows prolonged residence of the delivery system at the inflamed site in the colon, confirmed by the adhesion potential of thiolated nanoliposomes using in-vitro and in-vivo models. To further provide therapeutic efficacy thiolated nanoliposomes were loaded with gallic acid (GA), a natural compound known for its antibacterial, antioxidant, and potent anti-inflammatory properties. Consequently, Gallic Acid-loaded Thiolated 2,6 DALP DMPG (GATh@APDL) demonstrates the potential for targeted adhesion to the inflamed colon, facilitated by their small size 100 nm and anionic nature. Therapeutic studies indicate that this formulation offers protective effects by mitigating colonic inflammation, downregulating the expression of NF-κB, HIF-1α, and MMP-9, and demonstrating superior efficacy compared to the free GA enema. The encapsulated GA inhibits the NF-κB expression, leading to enhanced expression of MUC2 protein, thereby promoting mucosal healing in the colon. Furthermore, GATh@APDL effectively reduces neutrophil infiltration and regulates immune cell quantification in colonic lamina propria. Our findings suggest that GATh@APDL holds promise for alleviating UC and addressing the limitations of conventional enema therapy.

Five commonly used traditional Chinese medicine formulas in the treatment of ulcerative colitis: A network meta-analysis.

Currently, traditional Chinese medicine (TCM) formulas are commonly being used as adjunctive therapy for ulcerative colitis in China. Network meta-analysis, a quantitative and comprehensive analytical method, can systematically compare the effects of different adjunctive treatment options for ulcerative colitis, providing scientific evidence for clinical decision-making. To evaluate the clinical efficacy and safety of commonly used TCM for the treatment of ulcerative colitis (UC) in clinical practice through a network meta-analysis. Clinical randomized controlled trials of these TCM formulas used for the adjuvant treatment of UC were searched from the establishment of the databases to July 1, 2022. Studies that met the inclusion criteria were screened and evaluated for literature quality and risk of bias according to the Cochrane 5.1 standard. The methodological quality of the studies was assessed using ReviewManager (RevMan) 5.4, and a funnel plot was constructed to test for publication bias. ADDIS 1.16 statistical software was used to perform statistical analysis of the treatment measures and derive the network relationship and ranking diagrams of the various intervention measures. A total of 64 randomized controlled trials involving 5456 patients with UC were included in this study. The adjuvant treatment of UC using five TCM formulations was able to improve the clinical outcome of the patients. Adjuvant treatment with Baitouweng decoction (BTWT) showed a significant effect [mean difference = 36.22, 95% confidence interval (CI): 7.63 to 65.76]. For the reduction of tumor necrosis factor in patients with UC, adjunctive therapy with BTWT (mean difference = -9.55, 95%CI: -17.89 to -1.41), Shenlingbaizhu powder [SLBZS; odds ratio (OR) = 0.19, 95%CI: 0.08 to 0.39], and Shaoyao decoction (OR = -23.02, 95%CI: -33.64 to -13.14) was effective. Shaoyao decoction was more effective than BTWT (OR = 0.12, 95%CI: 0.03 to 0.39), SLBZS (OR = 0.19, 95%CI: 0.08 to 0. 39), and Xi Lei powder (OR = 0.34, 95%CI: 0.13 to 0.81) in reducing tumor necrosis factor and the recurrence rate of UC. TCM combined with mesalazine is more effective than mesalazine alone in the treatment of UC.

Sustained release of 5-aminosalicylic acid from azoreductase-responsive polymeric prodrugs for prolonged colon-targeted colitis therapy

Ulcerative colitis (UC) is a challenging inflammatory gastrointestinal disorder, whose therapies encounter limitations in overcoming insufficient colonic retention and rapid systemic clearance. In this study, we report an innovative polymeric prodrug nanoformulation for targeted UC treatment through sustained 5-aminosalicylic acid (5-ASA) delivery. Amphiphilic polymer-based 13.5 nm micelles were engineered to incorporate azo-linked 5-ASA prodrug motifs, enabling cleavage via colonic azoreductases. In vitro, micelles exhibited excellent stability under gastric/intestinal conditions while demonstrating controlled 5-ASA release over 24 h in colonic fluids. Orally administered micelles revealed prolonged 24-h retention and a high accumulation within inflamed murine colonic tissue. At an approximately 60% dose reduction from those most advanced recent studies, the platform halted DSS colitis progression and outperformed standard 5-ASA therapy through a 77–97% suppression of inflammatory markers. Histological analysis confirmed intact colon morphology and restored barrier protein expression. This integrated prodrug nanoformulation addresses limitations in colon-targeted UC therapy through localized bioactivation and tailored pharmacokinetics, suggesting the potential of nanotechnology-guided precision delivery to transform disease management.