Small Intestine Research Articles (Page 1)

Ileum targeted semaglutide delivery and pharmacokinetic study in an experimental porcine animal model via oesophagogastroduodenoscopic administration.

Pelvic abscess (PA) is a serious complication of pelvic exenteration (PE) that adversely affects patient outcomes. Although various procedures, including flap reconstruction, have been challenged, definitive indications have not been established. This study aims to identify the risk factors for PA following total PE (TPE). The subjects of this retrospective study were 107 consecutive patients who underwent TPE for locally advanced or recurrent pelvic tumors between June, 2006 and July, 2019. We analyzed the perioperative risk factors for PA, defined as infectious fluid collection in the deep pelvis requiring drainage. PA developed in 37 patients (34.6%), whose postoperative hospital stay was significantly longer than that of patients without PA (53days vs. 32days, P < 0.01). Among the presurgical and surgical factors, bony pelvic resection was an independent predictor of PA (OR: 4.94; 95% CI: 1.57-15.54; P = 0.01). Computed tomography (CT) findings of fluid accumulation and the absence of small intestine in the deep pelvis correlated significantly with PA incidence (P = 0.02, respectively). Bony pelvic resection is a key risk factor for PA following TPE. Consequently, filling the pelvic dead space with a myocutaneous flap could be considered to reduce the risk of PA in patients undergoing bony pelvic resection.

Microbial overgrowth (MO) in the small intestine can cause gastrointestinal symptoms and may arise from stasis, such as dysmotility. Microtypes of MO include small intestinal bacterial overgrowth (SIBO) and intestinal methanogen overgrowth (IMO). Dyssynergic defecation (DD) is associated with constipation and slow colonic transit (STC). Our aim was to assess the relationship between DD and MO. We retrospectively identified patients who underwent both anorectal manometry (ARM) and balloon expulsion testing (BET) for DD, and MO testing using either small intestinal aspirate culture or breath testing. SIBO was analyzed using two culture thresholds: ≥ 105 CFU/mL and ≥ 103 CFU/mL. Chi-square tests compared positive vs. negative results. 436 patients underwent culture of SB aspirates. At the ≥ 105 CFU/mL threshold, 41.7% were diagnosed with SIBO, and 87.4% at ≥ 103 CFU/mL. At ≥ 105 CFU/mL, percent anal relaxation was significantly lower in SIBO-positive patients. SIBO patients were more likely to have reduced anal relaxation (p = 0.032), but no other ARM parameters or BET > 60 s. At ≥ 103 CFU/mL, a more negative recto-anal pressure differential (RAPD) was observed, along with a combination of RAPD < -45 mmHg and resting anal pressure > 90 mmHg. 637 patients underwent breath testing for MO, with 174 positive results, predominantly showing IMO (73%). In this group, BET was significantly longer, and anal relaxation was significantly lower. SIBO at ≥ 103 CFU/mL was more prevalent in DD than STC (85.5% vs. 64.7%, p = 0.002). IMO was more common in DD than STC (p = 0.021). DD may be a risk factor for MO, often with evidence of methanogenesis.

BACKGROUND Gastrointestinal bleeding due to metastasis of an invasive mole to the small intestine is very rare. Most reported cases of metastatic invasive mole are diagnosed after surgery, and lack rich illustrations, which leads to insufficient understanding by clinicians, misdiagnosis, and unnecessary surgeries. CASE SUMMARY A 22-year-old female patient presented with bloody stool and elevated human chorionic gonadotropin. The transvaginal gynecological ultrasound ruled out pregnancy. Upper gastrointestinal endoscopy and colonoscopy were performed, but no bleeding focus was detected. The contrast-enhanced computed tomography was unremarkable. The capsule endoscopy suggested jejunal protuberant lesions with dark red blood clots. Therefore, oral single-balloon enteroscopy was performed, and two connected protuberant lesions were detected, with blood clot traces and local ulceration. The enteroscopic biopsy revealed trophoblastic cells with a probable diagnosis of trophoblastic tumor. The patient underwent surgical resection of the diseased jejunum. Intraoperative endoscopy was performed, and the findings were the same as those of the small intestine endoscopy. The postoperative pathology confirmed the preoperative diagnosis of invasive mole. CONCLUSION In non-pregnant women with elevated human chorionic gonadotropin and gastrointestinal bleeding, metastatic trophoblastic neoplasia should be considered.

The gastrointestinal tract (GIT) of cattle plays a vital role in nutrient absorption, immune function, and microbial homeostasis. While the importance of the GIT microbiome and epithelial barrier integrity has been increasingly recognized, the typical composition of microbial communities and the expression of tight junction proteins (TJPs) in feedlot cattle remains poorly characterized. We investigated microbial community structure and TJP expression at three GIT sites: the rumen (RU), small intestine (SI), and large intestine (LI) in 21 finish-fed feedlot steers sourced from 21 commercial feedyards in the Texas Panhandle. Samples of luminal contents and GIT tissue were collected from each region, as well as feces and liver abscess material. Microbial communities were characterized using 16S rRNA gene sequencing. TJP gene expression was quantified by RT-qPCR using synthetic standards, and protein expression was evaluated by immunohistochemistry (IHC) with both computer-generated and pathologist-generated scoring. Microbial community structures varied primarily by GIT region rather than by individual animals raised at different locations. Nine bacterial families were identified as core microbiome members, with Lachnospiraceae being the most abundant across the GIT. TJP gene expression varied considerably by site, with RU having significantly lower Claudin 1, Claudin 2, and E-Cadherin expression than the SI and LI. IHC results paralleled qPCR findings, with region-specific patterns of protein localization and intensity. Computerized and pathologist-generated H-scores showed moderate agreement but differed notably between epithelial and lamina propria regions. This study provides a comprehensive baseline of microbial and host factors associated with gut health in a uniquely diverse population of feedlot cattle. The identification of regional microbial communities and distinct TJP expression patterns offers foundational insights into gastrointestinal physiology and barrier function. This work establishes baseline data to support future investigations into the relationships among microbial ecology, epithelial barrier function, and cattle health and productivity.

An endoscopically placed duodenal-jejunal bypass liner (DJBL) may provide a safe adjunctive therapy for those with poorly controlled type 2 diabetes mellitus (T2DM) and obesity. While some endoscopic therapies have been shown to improve glycemic indices secondary to weight loss, small bowel interventions may have direct metabolic effects. A meta-analysis of observational studies demonstrated reduction in HbA1c by 1.3% at one year following DJBL in patients with T2DM and obesity. This was a multicenter, double-blind, randomized, sham-controlled trial comparing DJBL to sham procedure with medical management and lifestyle modification. Primary endpoints included mean difference in changes in HbA1c at 12 months between arms, and device-related serious adverse events (SAEs). Secondary endpoints included percent total weight loss (%TWL) and subjects achieving HbA1c≤7% and TWL≥5% at 12 months. 320 subjects were randomized to DJBL (n=212) and sham (n=108). Baseline HbA1c and BMI were 8.79±0.92% and 38.45±5.75kg/m2. On modified intent-to-treat analysis, change in HbA1c at 12 months was -1.10±1.45% and -0.28±1.54% for DJBL and sham groups, respectively (P=0.0004). Rate of device-related SAEs was 9.4% including intolerance (3.7%), hemorrhage (2.8%) and hepatic abscess (2.3% stopping study early). At 12 months, DJBL group experienced greater weight loss compared to sham (7.7±9.6% TWL and 2.1±5.4% TWL, respectively; P<0.0001), with significantly more patients achieving HbA1c ≤ 7% (28.3% vs. 9.4%; P<0.0003) and TWL ≥ 5% (60.4% vs. 21.3%; P<0.0001). DJBL met primary glycemic control efficacy and primary safety endpoints, while providing clinically significant weight loss, and comorbidity improvement.

A 1-year-old boy presenting with irritability, lethargy and vomiting was diagnosed with small bowel volvulus due to intestinal malrotation. Prompt surgical intervention prevented severe complications. The case highlights the importance of considering acute abdominal conditions in infants with altered consciousness and the utility of abdominal ultrasound as a rapid diagnostic tool.

Fructose malabsorption is characterized as the incomplete absorption of fructose in the small intestine. Fructose is one of the most common monosaccharides in the human diet. The purpose of this review is to provide an updated overview of insights into the relationship between high-fructose diet, fructose malabsorption, gut microbiota and clinical consequences. Incomplete absorption of fructose causes accumulation in the colon, which leads to fermentation by gut microbiota and abdominal symptoms such as bloating and excessive gas production. Malabsorption may result from exceeding the absorptive capacity of GLUT5 or insufficient upregulation, with incidence increasing with age and higher dietary fructose concentrations. High-fructose diets generally promote an increase in inflammatory bacterial groups such as Desulfovibrio and Deferribacteraceae, while reducing beneficial Bacteroidetes. These microbial alterations may impair intestinal barrier function, modify short-chain fatty acid profiles, and contribute to systemic inflammation, metabolic disorders, and potentially mental health issues. Animal studies using fructose malabsorption models present inconclusive results regarding the impact of fructose on the composition of gut microbiota. Additional research is essential to fully comprehend the complex relationship between diet, fructose malabsorption and gut microbiota, to develop personalized, effective dietary approaches for managing symptoms of fructose malabsorption.

Acute enterocolitis encompasses a broad spectrum of conditions affecting the small and large bowel, frequently presenting with nonspecific symptoms such as abdominal pain, diarrhea, fever, and vomiting. Given the clinical overlap among infectious, inflammatory, immune-mediated, vascular, and miscellaneous etiologies, imaging plays a pivotal role in refining the differential diagnosis, identifying complications, and guiding timely management. Computed tomography (CT), owing to its accessibility and rapid acquisition, remains the cornerstone of imaging evaluation in acute settings. CT enables detailed assessment of bowel wall morphology, disease distribution, vascular involvement, and extraintestinal manifestations. While ancillary imaging modalities have a role in select scenarios, this review emphasizes a CT-focused approach tailored for acute care. We present a comprehensive, pattern-based review of the CT imaging features across various forms of acute enterocolitis, highlighting diagnostic hallmarks, interpretive pitfalls, and clinically relevant mimics. The included cases were encountered by the radiologists in their day-to day practice and included based on their ability to highlight the majority representative features of each pathology. Through the integration of structured tables, illustrative cases, and diagnostic tips, this article aims to enhance the radiologist's ability to recognize key imaging signatures, avoid diagnostic errors, and contribute meaningfully to multidisciplinary patient care.

Video Capsule Endoscopycapsule endoscopy (VCE) has emerged as a minimally invasive diagnostic tool for detecting and monitoring small bowel involvement in polyposis syndromes. VCE is included in the surveillance guidelines of Peutz-Jeghers syndrome. In the remaining familial polyposis syndromes, VCE may facilitate the early detection of polyps, when indicated, particularly in areas beyond the reach of conventional endoscopy, thereby aiding timely detection. Colon capsule endoscopy has been studied in symptomatic, screening and polyp surveillance populations and the second-generation colon capsule has demonstrated excellent detection rates for advanced neoplasia, however its role in colonic polyposis requires further research. The role of the panenteric capsule has not been explored in polyposis syndromes as a panintestinal examination. Despite its advantages, VCE has notable limitations; it may miss small, flat, or hidden lesions and lacks the capability for tissue sampling or therapeutic intervention. In the future, advances in imaging technology, extended battery life, and the integration of artificial intelligence (AI) are expected to further enhance the utility of VCE. Our review aims to focus on the applications of VCE in polyposis syndromes and future perspectives.

Background A great heterogeneity exists among patients with chronic intestinal failure even with the same intestinal circuit. Weaning from parenteral support depends on intestinal adaptation, remnant bowel length, and functional capacity. The present study aimed to assess if pre-existent nutritional reserves would predict the possibility of enteral autonomy. Methods This retrospective observational study evaluated the incidence of weaning off parenteral support in adult patients with chronic intestinal failure due to short bowel syndrome from an Italian referral center. Multivariable models, considering mortality as a competing risk, identified predictors of weaning. Results Out of 251 patients, 116 (46.2%) died without being weaned and 76 (30.3%) were weaned off. The latter showed increased residual small bowel length, more frequently the colon-in-continuity and the ileocecal valve, lower age, higher weight and BMI (25.3 ± 5.6 vs 20.9 ± 3.2 kg/m 2 ) at parenteral support starting. In a multivariable competing risk model, age [sub-distribution hazard ratio (SHR) 0.82; 95%CI 0.71–0.95], small bowel length (SHR = 1.11; 1.06–1.15), type 2 (SHR = 2.63; 1.37–5.02) and type 3 short bowel syndrome (SHR = 6.85; 3.45–13.60), and BMI at enrolment (SHR = 1.11; 1.06–1.15) were significantly associated with weaning off. Body composition by bioelectrical impedance was assessed in a subgroup ( n = 147). Patients who weaned displayed increased intracellular water as total water percentage, phase angle and muscle mass index. At multivariable analyses, % intracellular water was a significant predictor of weaning (SHR = 1.06; 1.03–1.09). Conclusion Patients with chronic intestinal failure due to short bowel syndrome with increased BMI and a healthier body composition were more likely to be weaned off parenteral nutrition.

Diarrhoea is a global health issue affecting all regions and populations, particularly in low and middle-income countries of sub-Saharan Africa and Asia from where the very young and old aged are more vulnerable. The conventional belief that extracts of sweet potato leaves are effective in the treatment of diarrhoea is not supported by any statistical evidence from the scientific community. Therefore, the present study aimed to screen the crude extracts of sweet potato for its secondary metabolites, acute toxicity, antioxidant enzyme, and antidiarrhoeal activity at 125, 250, and 500 mg/kg bw in a Wistar rat model. Methanol and n-hexane extracts of sweet potato (Ipomoea batatas) leaves were tested for antidiarrhoeal activity using castor oil-induced models in rats. The most active extracts were screened for elemental compositions using standard methods. The crude extracts revealed the presence of flavonoids, saponins, alkaloids, tannins, and terpenes. The LD50 of the extracts was found to be greater than 5000 mg/kg body weight of the rats. The elemental analysis of the most active extract revealed the presence of zinc (Zn), potassium (K), sodium (Na), and chloride (Cl). Both extracts delayed diarrhoea onset and reduced faecal frequency and water content significantly (p&lt;0.05), with the methanol extract showing greater inhibition (~66.5%) at 500 mg/kg compared to controls. Na+-K+-ATPase, alkaline phosphatase, and catalase activity in the small intestine increased significantly (p &lt; 0.05) as the dose of crude extracts increased, whereas crude extract produced dose-specific dependent on intestinal superoxide dismutase activity and nitric oxide concentration. The GC-MS analysis carried out on the most active extract revealed that the extract is composed of gallo-tannins (71.27%), n-Hexadecanoic acid (23.53%), catechol (2.57%), methylgallate (1.59%), propanoic acid, 2-(aminoxy) (0.92%), and trigonelline (0.10%). These compounds were found to be the most abundant in the extract.

Maladaptive host metabolic responses to infection are emerging as major determinants of infectious disease pathogenesis. However, the factors regulating these metabolic changes within tissues remain poorly understood. In this study, we used toxoplasmosis, as a prototypical example of a disease regulated by strong type I immune responses, to assess the relative roles of current local parasite burden, local tissue inflammation, and the microbiome in shaping local tissue metabolism during acute and chronic infections. Toxoplasmosis is a zoonotic disease caused by the parasite Toxoplasma gondii. This protozoan infects the small intestine and then disseminates broadly in the acute stage of infection, before establishing chronic infection in the skeletal muscle, cardiac muscle, and brain. We compared metabolism in 11 sampling sites in C57BL/6 mice during the acute and chronic stages of T. gondii infection. Strikingly, major spatial mismatches were observed between metabolic perturbation and local parasite burden at the time of sample collection for both disease stages. By contrast, a stronger association with indicators of active type I immune responses was observed, indicating a tighter relationship between metabolic perturbation and local immunity than with local parasite burden. Loss of signaling through the IL1 receptor in IL1R knockout mice was associated with reduced metabolic impact of infection. In addition, we observed significant changes in microbiota composition with infection and candidate microbial origins for multiple metabolites impacted by infection. These findings highlight the metabolic consequences of toxoplasmosis across different organs and potential regulators.IMPORTANCEInflammation is a major driver of tissue perturbation. However, the signals driving these changes on a tissue-intrinsic and molecular level are poorly understood. This study evaluated tissue-specific metabolic perturbations across 11 sampling sites following systemic murine infection with the parasite Toxoplasma gondii. Results revealed relationships between differential metabolite enrichment and variables, including inflammatory signals, pathogen burden, and commensal microbial communities. These data will inform hypotheses about the signals driving specific metabolic adaptation in acute and chronic protozoan infection, with broader implications for infection and inflammation in general.

Solid lipid nanoparticles (SLNs) have garnered significant interest for their safety and efficacy, especially following the success of COVID-19 mRNA vaccines. This study presents the synthesis and characterization of a novel stearic acid (SA)-gambogic acid (GA) conjugate, where GA, a xanthonoid, exhibits high affinity for the transferrin receptor (TfR) without competing with endogenous transferrin. The SA-GA conjugate was employed to formulate SLNs using a hot homogenization-ultrasonication-solvent evaporation technique for the peroral delivery of cyclosporine (CsA), paclitaxel (PTX), and urolithin-A (UA). Physicochemical properties, including particle size, zeta potential, drug loading, and entrapment efficiency, were assessed. Among the three tested compounds, UA exhibited the highest encapsulation efficiency at both 5% and 10% w/w loading, with particle sizes remaining under 250nm. SA-GA SLNs demonstrated excellent stability in simulated gastric fluids, supporting their potential for oral administration. Cellular uptake studies using Coumarin-6 (C6) and drug-loaded SLNs indicated that UA achieved the highest uptake (~ 50%) in both FHS-74 (human small intestine) and HK2 (human kidney) cell lines. Further, in cisplatin-induced HK2 cell damage models, UA-loaded SA-GA SLNs significantly reduced inflammatory markers TLR4, NF-κB, and IL-1β. These results highlight UA-loaded SA-GA SLNs as a promising TfR-targeted oral delivery system for mitigating cisplatin-induced acute kidney injury (AKI) in cancer therapy.

Introduction and Definition: Celiac Disease (CD) is an autoimmune disorder affecting the small intestine, triggered by an abnormal immune response to gluten, a protein found in wheat, barley, and rye. Although its roots date back to the 2nd century AD, the condition was first identified by English physician Samuel Gee in 1888, who hypothesized dietary changes as beneficial. Today, the National Institute of Diabetes and Digestive and Kidney Diseases defines CD as "a chronic digestive and immune disorder that damages the small intestine". CD affects about 1% of the global population, yet about 80% of cases go undiagnosed. This significant underdiagnosis highlights the need for greater awareness and research, as delayed diagnosis can cause complications and reduce quality of life. Causes: Gluten consumption in individuals carrying the HLA-DQ2 and HLA-DQ8 genetic alleles causes inflammation in the small intestine, leading to villous atrophy (damage to nutrient-absorbing villi). Beyond genetics, environmental factors such as early-life gluten exposure, gastrointestinal infections, frequent early-life illnesses, and microbiome (digestive bacteria) changes may contribute to disease onset in some cases. Symptoms and Diagnosis: CD symptoms vary widely, ranging from digestive issues like diarrhea and bloating to nutrient malabsorption problems like anemia, as well as systemic effects including osteoporosis, mental health issues, and reproductive problems. Timely diagnosis can prevent complications and often begins with blood tests to detect elevated levels of antibodies, followed by biopsies of the small intestine to confirm villous atrophy. Treatment and Management: The only current treatment for CD is a lifelong gluten-free diet, essential for healing the small intestine and alleviating symptoms. While vitamin and mineral supplements may help manage deficiencies, they do not heal the intestine. Effective management involves educating patients about CD, providing regular medical monitoring, and offering support for the social and emotional challenges associated with the condition. Current Research: Ongoing research explores enzyme therapies, vaccines, and microbiome-targeted treatments to supplement the gluten-free diet. Latiglutenase, a combination of enzymes that break down gluten, shows promise in reducing intestinal damage and symptoms from accidental gluten exposure, a common issue for patients. It is being considered as a possible additional therapy for CD.

IL-17A plays a crucial role in the immune defense against Giardia infection, yet its cellular sources remain incompletely defined. In this study, the site-specific expression and cellular origin of IL-17A were investigated, focusing on both adaptive and innate immune cells in the small intestine, Peyer's patches and mesenteric lymph nodes of Giardia muris infected C57BL/6 mice. RT-qPCR analyses showed that IL-17A mRNA expression was significantly upregulated in the small intestine, slightly elevated in the Peyer's patches and unchanged in the mesenteric lymph nodes. Flow cytometry revealed that CD4⁺ T helper cells in the lamina propria of the small intestine are the predominant source of anti-giardial IL-17A. No increase in IL-17A was detected by γδT cells, Tc cells, NK(T) cells, B cells, neutrophils, dendritic cells and innate lymphoid cells. Within the CD3- innate cell population, increased IL-17A production was observed in MHC-II+CD11c+CD11b+/- cells, including a subset of cells expressing typical macrophage markers, namely MHC-II⁺CD11c⁺CD11b⁺CD64⁺F4/80⁺ cells. In T cell-deficient mice, both IL-17A expression and parasite clearance were severely impaired. Our findings demonstrate the importance of the adaptive immunity and simultaneously identify Th cells in the lamina propria as the main source of anti-giardial IL-17A, with a possible supporting role from macrophage-like antigen-presenting cells.

Background and Objectives: Primary mesenteric liposarcoma (LPS) is an exceptionally rare malignancy, with most literature data limited to isolated case reports or small series. This papers aims to evaluate the clinicopathological features, treatment outcomes, and prognostic factors in patients with mesenteric LPS. Materials and Methods: Thirteen patients diagnosed with primary mesenteric LPS between 2010 and 2022 were retrospectively analyzed. Data included demographics, tumor location, histological subtype, surgical treatment, recurrence, and survival. Results: The median age was 56 years (range, 22–74), with a slight male predominance (53.8%). Most tumors arose from the small bowel (53.8%) and colonic (38.5%) mesenteries, with one involving the gastric mesentery. The predominant histological subtypes were myxoid (46.1%) and dedifferentiated (23.1%). R0 resection was achieved in 76.9% of patients. During a median follow-up of 55.2 months, nine patients (69.2%) developed recurrence. Mortality was higher in patients with dedifferentiated LPS (66.7%) than in those with myxoid LPS (40%). Five-year survival rate was 100% in patients without recurrence and 28.6% in those with recurrence (p = 0.112, not significant). Patients who received adjuvant chemoradiotherapy suggested longer survival (110.7 vs. 46.2 months; p = 0.620). Conclusions: This 12-year study highlights the aggressive nature of mesenteric LPS, particularly the dedifferentiated subtype which showed the poorest prognosis. Complete resection remains the primary treatment; however, it has high recurrence rates. To diminish the catastrophic poor results of the postoperative period, multidisciplinary treatment strategies become a keystone.

Background: Substance Use Disorders (SUDs) are a common and serious public health problem. In 2019, the overall death toll attributable to SUDs included 7.7 million deaths related to smoking, 2.4 million due to alcohol use, and approximately 0.5 million resulting from the use of other psychoactive substances. Treatment methods for SUDs typically include psychotherapy, pharmacotherapy, and neuromodulation techniques. Glucagon-like peptide-1 (GLP-1), produced mainly in the small intestine, exerts various peripheral effects. These properties have formed the basis for the use of GLP-1 analogues, initially in the treatment of type II diabetes and more recently in obesity and cardiovascular diseases. GLP-1 also exerts central nervous system effects, which has led to interest in its potential application in the treatment of SUDs.Aim of the study: The aim of this paper is to review the existing literature on randomized controlled trials (RCTs) evaluating the efficacy of GLP-1 analogues in reducing psychoactive substance use among patients with SUDs.Materials and Methods: The PubMed database was searched using the following terms: “GLP-1” AND (“addiction” OR “substance use”). Only clinical trials with a placebo or active control group were included.Results: A total of 321 papers were identified, of which 7 met the inclusion criteria. In total, 525 adult participants were included in the analysis, including patients diagnosed with nicotine use disorder (335 participants), alcohol use disorder (175 participants), and cocaine use disorder (13 participants).Conclusions: Three of the seven reviewed RCTs reported a significant reduction in substance use with GLP-1 receptor (GLP-1R) agonists compared to placebo. Another trial demonstrated similar efficacy only in a specific subgroup of obese participants. The remaining three studies did not report significant effects. Adverse events were common but generally mild and consistent with the known safety profile of GLP-1R agonists. GLP-1R agonists represent a promising new therapeutic approach; however, the limited number of trials and heterogeneity in inclusion criteria and treatment regimens highlight the need for more comprehensive and longer-term research.

Sinomenine (SIN) is a promising candidate for the treatment of rheumatoid arthritis (RA). Although it possesses the advantage of being non-addictive, its poor aqueous solubility and low oral bioavailability have limited its clinical application. To address these issues, SIN was encapsulated into lipid cubic liquid crystal nanoparticles (LCNPs) and systematically characterized. Molecular dynamics (MD) simulations were first employed to screen suitable excipients for formulation development. Combined with single-factor optimization and Box–Behnken response surface design, the optimal composition and preparation process were determined. The resulting SIN-LCNPs exhibited a particle size of 149.7 ± 0.9 nm, a polydispersity index (PDI) of 0.223 ± 0.01, a zeta potential of −18.9 mV, and an encapsulation efficiency (EE%) of 92.2%. Spectroscopic analyses confirmed successful incorporation of SIN into the lipid matrix. Pharmacodynamic studies revealed that SIN-LCNPs enhanced targeted drug delivery to inflamed joints, significantly alleviating inflammation and suppressing disease progression in rats. In vivo single-pass intestinal perfusion (SPIP) experiments further demonstrated that SIN was primarily absorbed through the small intestine and that the LCNP carrier effectively improved its intestinal permeability. Collectively, this study provides a novel strategy and theoretical foundation for developing efficient formulations of poorly water-soluble drugs, highlighting the potential clinical application of SIN-LCNPs in RA therapy.

A rare cause of partial small bowel obstruction