Regions Of Colon Research Articles

Form & formulation approaches for COntRollable Release in 3D printed Colonic Targeting (CORR3CT) budesonide tablet

Inflammatory bowel disease (IBD) represents a group of chronic and debilitating inflammatory diseases affecting various parts of the gastrointestinal (GI) tract. The disease incidence and prevalence have been growing worldwide since the early 21st century and this upward trend is expected to continue. Due to a complex and variable clinical presentation across different patients, the efficacy of a one-size-fits-all commercial formulation for IBD remains limited. Here, we present the development of a novel adjustable and controllable release, 3D printed colonic targeting (CORR3CT) dosage form of budesonide, to reduce off-targeting adverse effects and to potentially replace the use of enemas, which are invasive and commonly associated with poor adherence. An in vitro Gastrointestinal Simulated System (GISS) model was employed in this study to examine the ability of the 3D printed tablets to deliver budesonide to various targeted sites along the gastrointestinal tract. CORR3CT tablet with Pill-in-pill configurations were designed, fabricated and the relationship between the 3D printed design and resultant dissolution profiles were established. The 3D printed tablets also exhibited excellent and comparable dose accuracy and quality versus commercial tablets, while enhancing the delivery of budesonide to the targeted colon region. Overall, this study has laid the foundational proof of concept demonstrating controllable targeting of oral therapeutics along the gastrointestinal tract using 3D printing technologies.

Colorectal cancer: Current treatments and its novel drug delivery systems

Nowadays, one of the most common tumors in the world is colorectal cancer (CRC) which is increasing day by day and attributes to the mortality of many lives around the globe. It is also the second most lethal and third most widespread cancer diagnosis for both males and females. However, numerous inventive treatments had been developed for both primary and advanced colorectal cancer which include surgery, chemotherapy, immunotherapy, and utilizing some of the novel drug delivery systems. In the present review, we have attempted to address several innovative, novel treatment methods, procedures, and targeting strategies employing different polymers and drugs to deliver at colonic region. Also, the present review highlighted the applications of nanocarriers such as carbon nanotubes, gold nanoparticles, dendrimers, liposomes, hydrogels, and phytotomies for the effective treatment of CRC

Comparative transcriptomics reveals highly conserved regional programs between porcine and human colonic enteric nervous system

The porcine gut is increasingly regarded as a useful translational model. The enteric nervous system in the colon coordinates diverse functions. However, knowledge of the molecular profiling of porcine enteric nerve system and its similarity to that of human is still lacking. We identified the distinct transcriptional programs associated with functional characteristics between inner submucosal and myenteric ganglia in porcine proximal and distal colon using bulk RNA and single-cell RNA sequencing. Comparative transcriptomics of myenteric ganglia in corresponding colonic regions of pig and human revealed highly conserved programs in porcine proximal and distal colon, which explained >96% of their transcriptomic responses to vagal nerve stimulation, suggesting that porcine proximal and distal colon could serve as predictors in translational studies. The conserved programs specific for inflammatory modulation were displayed in pigs with vagal nerve stimulation. This study provides a valuable transcriptomic resource for understanding of human colonic functions and neuromodulation using porcine model.

Smart Diagnosis of Adenocarcinoma Using Convolution Neural Networks and Support Vector Machines

Adenocarcinoma is a type of cancer that develops in the glands present on the lining of the organs in the human body. It is found that histopathological images, obtained as a result of biopsy, are the most definitive way of diagnosing cancer. The main objective of this work is to use deep learning techniques for the detection and classification of adenocarcinoma using histopathological images of lung and colon tissues with minimal preprocessing. Two approaches have been utilized. The first method entails creating two CNN architectures: CNN with a Softmax classifier (AdenoCanNet) and CNN with an SVM classifier (AdenoCanSVM). The second approach corresponds to training some of the prominent existing architecture such as VGG16, VGG19, LeNet, and ResNet50. The study aims at understanding the performance of various architectures in diagnosing using histopathological images with cases taken separately and taken together, with a full dataset and a subset of the dataset. The LC25000 dataset used consists of 25,000 histopathological images, having both cancerous and normal images from both the lung and colon regions of the human body. The accuracy metric was taken as the defining parameter for determining and comparing the performance of various architectures undertaken during the study. A comparison between the several models used in the study is presented and discussed.

Efficient loading and delivery of ciprofloxacin by smart alginate/carboxylated graphene oxide/aminated chitosan composite microbeads: In vitro release and kinetic studies

New composite microbeads were formulated as smart pH-sensitive vehicle for efficient delivery of ciprofloxacin (CIP) drug. Herein, carboxylated graphene oxide (CGO) was successfully impregnated into alginate (Alg) microbeads, which were then coated with aminated chitosan (AmCs) layer to form core–shell Alg/CGO@AmCs composite microbeads. Diverse analysis tools comprising FTIR, TGA, XRD and SEM were employed to characterize the developed carriers, while their swelling profiles and pH-sensitivity were examined under different pHs. The results clarified that increasing CGO and AmCs concentrations in microbeads matrix greatly protected Alg microbeads from fast disintegration at colon pH and prolonged their swelling time. Moreover, about 94.65 % of CIP drug was successfully loaded by Alg/CGO@AmCs composite microbeads compared to 61.95 % for Alg microbeads, confirming their reduced porosity. The in vitro CIP-release profiles were investigated in simulated gastrointestinal conditions. Furthermore, increasing AmCs concentration in the outer shell of composite microbeads clearly minimized the CIP burst release at the colon region and offered a sustained release performance. Besides, the CIP release mechanism was well-described by korsmeyer-peppas kinetic model. The cytotoxicity study confirmed the potential safety of the Alg/CGO@AmCs composite microbeads with human cell viability reached 98.98 %, suggesting their applicability as smart carriers for oral delivery of antibiotics.

Phosphatidylserine-functionalized liposomes-in-microgels for delivering genistein to effectively treat ulcerative colitis.

Ulcerative colitis (UC) is an inflammatory disease involving ulcers in the colon and rectum. The conventional treatments for UC still have many limitations, such as non-specific release, adverse effects and low absorption, resulting in the poor bioavailability of therapeutic agents. To address these challenges, targeting delivery systems are required to specifically deliver drugs to the colonic site with controlled release. Herein, we present a novel microgel oral delivery system, loaded with liposome nanoparticles (Li NPs) containing a natural anti-inflammatory compound genistein (Gen) into alginate microgels, thereby achieving the targeted release of Gen in the colonic region and ameliorating UC symptoms. Initially, Gen was loaded into phosphatidylserine (PS)-functionalized Li NPs to form Gen@Li NPs with an average size of 245.9 ± 9.6 nm. In vitro assessments confirmed that Gen@Li NPs efficiently targeted macrophages and facilitated the internalization of Gen into cells. To prevent rapid degradation in the harsh gastrointestinal tract, Gen@Li NPs were further encapsulated into alginate microgels through electric spraying technology, forming Gen@Li microgels. In vivo distribution tests demonstrated that Gen@Li microgels possessed long-term retention in the colon and gradual release characteristics compared to Gen@Li NPs. Furthermore, in vivo experiments confirmed that Gen@Li microgels significantly alleviated UC symptoms in mice induced by dextran sulfate sodium salt (DSS) mainly through reducing the expression levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and promoting colonic mucosal barrier repair through upregulation of mucosal protein expression. This study shed light on the potential of utilizing oral administration of natural compounds for UC treatment.

Microwave assisted vanillin crosslinked chitosan/polycarbophil superporous hydrogels for biomedical application: Optimization and characterization

Among the numerous macromolecules used in the formulation of superporous hydrogels, naturally occurring polysaccharides like chitosan, alginate, psyllium etc., offer better sustainable building blocks with improved characteristics. Present research work emphasis on development, optimization and characterization of novel superporous hydrogel containing microwave assisted vanillin crosslinked chitosan/polycarbophil (CVP). The preparation of CVP superporous hydrogels was systematically optimized using full factorial design. Optimized CVP superporous hydrogels were subjected for FTIR, DSC and XRD. Residual solvent analysis was performed by gas chromatography. Surface morphology was analysed using SEM. Optimized CVP superporous hydrogel showed good swelling in a pH ranging from 1 to 8 and can be prepared in desired shape and size. FTIR studies revealed the presence of desirable interactions between the polymers. DSC thermograms exhibited differences in comparison to individual polymer thermograms. Residual solvent analysis by gas chromatography method revealed concentration of acetone, in formulation was within permissible limits as per the ICH guidelines. SEM images clearly revealed the formation of the interconnected pores and capillary channels throughout out the formulation. Overall, the current study signifies that the optimized CVP superporous hydrogel formulation can be successfully formulated and employed for regulated delivery of drugs to the GI tract, buccal cavity, colon, vaginal, and rectal region for both local and systemic action for varied therapeutic purposes because of its ability to swell faster in wide range of pH.

Preparation and Characterization of IL-22 mRNA-loaded Lipid Nanoparticles.

Interleukin-22 (IL-22) has been demonstrated as a critical regulator of epithelial homeostasis and repair; it showed an anti-inflammatory effect against ulcerative colitis. Local microinjection of IL-22 cDNA vector has been shown to be effective in treating ulcerative colitis in mouse models. However, microinjection comes with multiple technical challenges for routine colon-targeted drug delivery. In contrast, oral administration can get around these challenges and provide comparable efficacy. We showed in previous studies that oral administration of new lipid nanoparticles (nLNP)-encapsulated IL-22 mRNA targets the colon region and efficiently ameliorates colitis. This protocol describes the details of preparing and characterizing the nLNP-encapsulated IL-22 mRNA using three major lipids that mimic the natural ginger-derived nanoparticles. It provides an nLNP platform that can be used to orally deliver other types of nucleic acids to the colon.

Kolonoskopi Sırasında Hasta Pozisyonunun Değiştirilmesinin Kolonoskopi Süresi, İleal Entübasyon Oranı Ve Polip Sayısına Etkisi

Objective: Colonoscopy is universally considered as the conventional tool for the identification and removal of adenomatous polyps. The aim was to evaluate the effect of position change on the cecal and ileal intubation rates and the detection rate of polyps. In this way, it is aimed to accelerate the colonoscopy procedure time and increase its sensitivity. Methods: The study included 943 patients aged between 17 and 90 years presented for a diagnostic colonoscopy at our hospital surgery clinic from January 2008 to December 2018. Results: The results indicated significantly lower median cecal and ileal intubation time and higher polyps detection rate owing to change in the patient’s posture to supine than in the left lateral position during colonoscopy procedure (p<0.0001). Moreover, cecal (p<0.0001) and ileal (p=0.001) intubation time was negatively correlated with the number of polyps detected. The age of the participating patients was the demographic factor found to be positively correlated with the number of polyps detected (p<0.0001). Furthermore, changing the patient’s posture to supine led to an 11% increase in the polyp detection rate in the cecum, ascending colon, and hepatic flexure combined regions (p<0.0001). The odds of detection of polyps in this region were 2.11 (95%CI, 1.60-2.78) times higher in supine posture compared to the left lateral position. Conclusion: The above findings strengthen the relevance of the position of the patient in the polyp detection rate during colonoscopy procedures.

Micromotor Based Mini-Tablet for Oral Delivery of Insulin.

Diabetes is a metabolic disorder characterized by hyperglycemia due to defective insulin secretion or its biological dysfunction. However, frequent subcutaneous injection of insulin often results in discomfort and local tissue infection. Herein, we demonstrate the successful fabrication of a mini-tablet system based on self-propelled micromotors with biocompatibility and biodegradability for oral colon administration of insulin. The insulin layer is first constructed onto the surface of a magnesium based micromotor via electrostatic interactions, followed by a tableting process. The resulting mini-tablets are then coated with esterified starch with colonic degradation capability, thus achieving controlled release of the embedded micromotors in the colon region. In the meantime, autonomous movement of the released micromotors with a speed up to 76.22 μm·s-1 further results in enhanced colonic uptake and absorption of insulin, realizing long-term control of blood glucose for more than 5 h. Our micromotor based mini-tablet system can not only broaden the biomedical applications of emerging self-propelled micromotors but also offer an appealing strategy for oral administration of biomacromolecular drugs represented by insulin.

A comprehensive review on RNA interference-mediated targeting of interleukins and its potential therapeutic implications in colon cancer.

Colon cancer is the world's fourth leading cause of death. It is cancer of the latter part of the large intestine, i.e. the colon. Chronic inflammation over a long period also leads to the development of cancer. Cancer in the colon region is arduous to diagnose and is detected at a later stage when it metastasizes to other parts of the body like the liver, lungs, peritoneum, etc. Colon cancer is a great example of solid tumours associated with chronic inflammation. Although conventional therapies are effective, they lose their effectiveness beyond a certain point. Relapse of the disease occurs frequently. RNA interference (RNAi) is emerging as a great tool to specifically attack the cancer cells of a target site like the colon. RNAi deals with epigenetic changes made in the defective cells which ultimately leads to their death without harming the healthy cells. In this review, two types of epigenetic modulators have been considered, namely siRNA and miRNA, and their effect on interleukins. Interleukins, a class of cytokines, are major inflammatory responses of the body that are released by immune cells like leukocytes and macrophages. Some of these interleukins are pro-inflammatory, thereby promoting inflammation which eventually causes cancer. RNAi can prevent colon cancer by inhibiting pro-inflammatory interleukins.

An AI-Based Colonic Polyp Classifier for Colorectal Cancer Screening Using Low-Dose Abdominal CT.

Among the non-invasive Colorectal cancer (CRC) screening approaches, Computed Tomography Colonography (CTC) and Virtual Colonoscopy (VC), are much more accurate. This work proposes an AI-based polyp detection framework for virtual colonoscopy (VC). Two main steps are addressed in this work: automatic segmentation to isolate the colon region from its background, and automatic polyp detection. Moreover, we evaluate the performance of the proposed framework on low-dose Computed Tomography (CT) scans. We build on our visualization approach, Fly-In (FI), which provides "filet"-like projections of the internal surface of the colon. The performance of the Fly-In approach confirms its ability with helping gastroenterologists, and it holds a great promise for combating CRC. In this work, these 2D projections of FI are fused with the 3D colon representation to generate new synthetic images. The synthetic images are used to train a RetinaNet model to detect polyps. The trained model has a 94% f1-score and 97% sensitivity. Furthermore, we study the effect of dose variation in CT scans on the performance of the the FI approach in polyp visualization. A simulation platform is developed for CTC visualization using FI, for regular CTC and low-dose CTC. This is accomplished using a novel AI restoration algorithm that enhances the Low-Dose CT images so that a 3D colon can be successfully reconstructed and visualized using the FI approach. Three senior board-certified radiologists evaluated the framework for the peak voltages of 30 KV, and the average relative sensitivities of the platform were 92%, whereas the 60 KV peak voltage produced average relative sensitivities of 99.5%.

Human gut microbiota stratified by (+)-catechin metabolism dynamics reveals colon region-dependent metabolic profile

Catechins have proven to have several health benefits, yet a huge interindividual variability occurs. The metabolic potency of the colonic microbiota towards catechin is a key determinant of this variability. Microbiota from two donors – previously characterized as a fast and a slow converter– were incubated with (+)-catechin in vitro. The robustness of in vitro metabolic profiles was verified by well-fitted human trials. The colon region-dependent and donor-dependent patterns were reflected in both metabolic features and colonic microbiota composition. Upstream and downstream metabolites were mainly detected in the proximal and distal colons, respectively, and were considered important explanatory variables for microbiota clustering in the corresponding colon regions. Higher abundances of two catechin-metabolizing bacteria, Eggerthella and Flavonifractor were found in the distal colon compared to the proximal colon and in slow converter than fast converter. Additionally, these two bacteria were enriched in treatment samples compared to sham treatment samples.

A Comparative Analysis of the Socio-Demographic Development of the Cities in Siberia and Amazonia in the second half of the 20th century

The article examines the prospects of using a comparative analysis in the study of the socio-demographic processes in the Northeastern regions of Brazil (Amazonia) and Siberia. The authors hypothesize that one of the optimal cases for comparison with Siberia is Amazonia. A comparative analysis suggests that the compared cases (a set of objects, phenomena and processes) should have a number of similar and distinctive features, while at the same time having tangible differences. Despite the seeming heterogeneity, Amazonia and Siberia have many similarities. Among the elements of similarity, the frontier position stands out in the first place. Both Siberia and Amazonia were the regions of European colonization. Throughout the 20th century, Siberia continued to be a relatively undeveloped territory, in fact, still being a frontier. Brazil's Amazon plays a similar role. Both regions have a similar economic profile and act as resource regions that are rich in timber, metals and other minerals as well as having similar energy profiles. The article highlights that the development in both regions peaked in the second half of the 20th century, and also discusses similar phenomena in the demographic processes in these regions. The findings have allowed the authors to formulate the main directions for further comparative analysis of the socio-demographic development of the large urban centers in Siberia and Amazonia.

Hydrolytic Quinoa Protein and Cationic Lotus Root Starch-Based Micelles for Co-Delivery of Quercetin and Epigallo-catechin 3-Gallate in Ulcerative Colitis Treatment.

The accumulation and sustained release of drugs in the colonic inflammatory region are the favorable strategy for treating ulcerative colitis (UC). In this study, we developed a synergistic anti-inflammatory drug (quercetin/EGCG)-loaded micelle using hydrolytic quinoa protein (HQP) and cationic lotus root starch (CLRS) by a layer-by-layer assembly method. The encapsulation efficiency of quercetin and EGCG in the Que-HQP-EGCG-CLRS micelles reached 91.5 and 89.4%, respectively. This composite micelle exhibited a core-shell structure, where Que-HQP-EGCG was the core and CLRS was the coating shell. Moreover, the in vitro experiments indicated that these micelles can make Que/EGCG pass through gastric environments stably and delay their release in the intestine. Animal experiments further confirmed that the Que-HQP-EGCG-CLRS micelles can efficiently accumulate in the colonic inflammatory region and enable sustained release of drugs (more than 24 h), thus notably alleviating the symptoms of UC. These results suggested that Que-HQP-EGCG-CLRS micelles have good gastric stability, colonic inflammatory-accumulated effect, and sustained drug release ability, which are a promising co-delivery system for UC treatment.

Distinct pretreatment innate immune landscape and posttreatment T cell responses underlie immunotherapy-induced colitis.

Immune-related adverse events represent a major hurdle to the success of immunotherapy. The immunological mechanisms underlying their development and relation to antitumor responses are poorly understood. By examining both systemic and tissue-specific immune changes induced by combination anti-CTLA-4 and anti-PD-1 immunotherapy, we found distinct repertoire changes in patients who developed moderate-severe colitis, irrespective of their antitumor response to therapy. The proportion of circulating monocytes were significantly increased at baseline in patients who subsequently developed colitis compared with patients who did not develop colitis, and biopsies from patients with colitis showed monocytic infiltration of both endoscopically and histopathologically normal and inflamed regions of colon. The magnitude of systemic expansion of T cells following commencement of immunotherapy was also greater in patients who developed colitis. Importantly, we show expansion of specific T cell subsets within inflamed regions of the colon, including tissue-resident memory CD8+ T cells and Th1 CD4+ T cells in patients who developed colitis. Our data also suggest that CD8+ T cell expansion was locally induced, while Th1 cell expansion was systemic. Together, our data show that exaggerated innate and T cell responses to combination immunotherapy synergize to propel colitis in susceptible patients.

First-line antibiotic treatment in patients with localized extragastric mucosa-associated lymphoid tissue lymphoma.

Between January 2010 and December 2015, we enrolled 28 patients with stage IEI/IIE1 extragastric mucosa-associated lymphoid tissue (MALT) lymphoma who received first-line antibiotic treatment, after informing them about the pros and cons of alternative therapies. In addition, during the same period, 64 patients with stage IE/IIE1 disease who received conventional treatment were selected as the control group. The most common primary sites were the ocular adnexal area (17 cases), followed by the salivary glands (four cases), pulmonary (three cases), and thyroid, trachea, larynx, and colon region (one case each). First-line antibiotic treatment resulted in an overall response rate of 57.1%: 12 patients achieved complete remission (CR), while four achieved partial remission (antibiotic-responsive tumors). Monoclonal gammopathy was significantly prevalent in antibiotic-unresponsive tumors than in antibiotic-responsive tumors (50.0% [6/12] vs. 12.5% [2/16], p=0.044). After a median follow-up of 7years, all patients with CR remained lymphoma-free, with 7-year event-free survival (EFS) and overall survival (OS) rates of 62.7% and 96.4%, respectively. The 7-year EFS and OS rates of patients who received conventional treatments were 73.1% and 91.1%, respectively. Compared with that noted in patients who received conventional treatment, antibiotic treatment was effective in some patients with localized extragastric MALT lymphoma.

Redox responsive poly(allylamine)/eudragit S-100 nanoparticles for dual drug delivery in colorectal cancer

Herein, we report redox responsive, colon cancer targeting poly(allylamine) (PA)/eudragit S-100 (EU) nanoparticles (PAEU NPs) (≈59 nm). These disulfide crosslinked PAEU NPs are developed via air oxidation of thiolated PA and thiolated EU, eliminating the need of any external crosslinking agent for dual drug delivery. PAEU NPs can effectively encapsulate both hydrophilic doxorubicin (DOX) and hydrophobic curcumin (Cur) drug with ≈85 % and ≈97 % encapsulation efficiency respectively. Here, the combination of drugs having different anticancer mechanism offers the possibility of developing nanosystem with enhanced anticancer efficacy. The developed PAEU NPs show good colloidal stability and low drug release under physiological conditions, while high DOX (≈98 %) and Cur (≈93 %) release is observed in reducing environment (10 mM GSH). Further, DOX and Cur loaded PAEU NPs exhibit higher cancer cell killing efficiency as compared to individual free drugs. In vivo biodistribution studies with Balb/C mice display the retention of PAEU NPs in the colon region up to 24 h presenting the developed approach as an efficient way for colorectal cancer therapy.

3D Printed Fractal-like Structures with High Percentage of Drug for Zero-Order Colonic Release.

Colonic drug delivery of drugs is an area of great interest due to the need to treat high prevalence colonic local diseases as well as systemic conditions that may benefit from the advantages associated to this route of drug administration. In the last decade, the use of 3D printing technologies has expanded, offering the possibility of preparing personalized medicines in small batches directly at the point of care. The aim of this work is to design a high drug loaded 3D printed system prepared by a combination of Fused Deposition Modelling (FDM) and Injection Volume Filling (IVF) techniques intended for zero-order colonic drug release. For this purpose, different batches of binary and ternary filaments based on the thermoplastic polyurethane Tecoflex EG-72D (TPU), theophylline anhydrous (AT) as model drug, and magnesium stearate as lubricant have been developed and characterized. Filaments with the highest drug load and the best rheological properties were selected for the manufacture of a printed fractal-like structure based on multiple toroids. This design was proposed to provide high surface area, leading to increased drug release and water uptake in the colonic region. This structure was 3D printed by FDM and then coated in a unique step by IVF technology using the enteric polymer DrugCoat S 12.5. This way, an additional coating process is avoided, reducing costs and production time. Studies of drug release confirmed the ability of the structures to provide a five-hour period of constant drug delivery in the colonic region.

Persistence of the Probiotic Lacticaseibacillus rhamnosus Strain GG (LGG) in an In Vitro Model of the Gut Microbiome.

The consumption of probiotics is widely encouraged due to reports of their positive effects on human health. In particular, Lacticaseibacillus rhamnosus strain GG (LGG) is an approved probiotic that has been reported to improve health outcomes, especially for gastrointestinal disorders. However, how LGG cooperates with the gut microbiome has not been fully explored. To understand the interaction between LGG and its ability to survive and grow within the gut microbiome, this study introduced LGG into established microbial communities using an in vitro model of the colon. LGG was inoculated into the simulated ascending colon and its persistence in, and transit through the subsequent transverse and descending colon regions was monitored over two weeks. The impact of LGG on the existing bacterial communities was investigated using 16S rRNA sequencing and short-chain fatty acid analysis. LGG was able to engraft and proliferate in the ascending region for at least 10 days but was diminished in the transverse and descending colon regions with little effect on short-chain fatty acid abundance. These data suggest that the health benefits of the probiotic LGG rely on its ability to transiently engraft and modulate the host microbial community.