Colon Targeted Drug Delivery System Research Articles

Dual targeting total saponins of Pulsatilla of natural polymer crosslinked gel beads with multiple therapeutic effects for ulcerative colitis

Oral colon targeted drug delivery system (OCTDDS) is desirable for the treatment of ulcerative colitis (UC). In this study, we designed a partially oxidized sodium alginate-chitosan crosslinked microsphere for UC treatment. Dissipative particle dynamics (DPD) was used to study the formation and enzyme response of gel beads from a molecular perspective. The formed gel beads have a narrow particle size distribution, a compact structure, low cytotoxicity and great colon targeting in vitro and in vivo. Animal experiments demonstrated that gel beads promoted colonic epithelial barrier integrity, decreased the level of pro-inflammatory factors, accelerated the recovery of intestinal microbial homeostasis in UC rats and restored the intestinal metabolic disorders. In conclusion, our gel bead is a promising approach for the treatment of UC and significant for the researches on the pathogenesis and treatment mechanism of UC.

A Novel Approach on Nanosphere Based Colon Targeted Drug Delivery System

Oral route is the most feasible and desired one, CDDS may also employ alternative methods. When administering medications directly to the colon, rectal administration is the fastest method. Rectal administration makes it challenging to reach the proximal portion of the colon. Rectal administration may potentially cause patients discomfort and result in poor compliance. Particles with a diameter between 10 and 200 nm are known as nanospheres. Nanospheres can be crystalline or amorphous in form, and they can shield a medicine from enzymatic and chemical deterioration. When treating colonic illness, targeted drugdelivery to the colon ensures direct therapy at the afflicted area with a lower dose and less systemic adverse effects and provides an appropriate environment for proteins and peptides that are susceptible to gastric fluid and digestive enzymes. It also minimizes the first pass metabolism advantage of the standard dose form and prevents gastrointestinal discomfort brought on by the ingestion of NSAIDs.
 Keywords: Nanospheres, CDDS, Nanoparticles, NSAID, gastrointestinal discomfort

Current Advances of Nanomaterial-Based Oral Drug Delivery for Colorectal Cancer Treatment.

Colorectal cancer (CRC) is a common malignant tumor, and traditional treatments include surgical resection and radiotherapy. However, local recurrence, distal metastasis, and intestinal obstruction are significant problems. Oral nano-formulation is a promising treatment strategy for CRC. This study introduces physiological and environmental factors, the main challenges of CRC treatment, and the need for a novel oral colon-targeted drug delivery system (OCDDS). This study reviews the research progress of controlled-release, responsive, magnetic, targeted, and other oral nano-formulations in the direction of CRC treatment, in addition to the advantages of oral colon-targeted nano-formulations and concerns about the oral delivery of related therapeutic agents to inspire related research.

A REVIEW ON DEVELOPMENT OF COLON TARGETED DRUG DELIVERY SYSTEM

The purpose of this review was to select a promising drug delivery system for colon diseases. This review covers the development of Colon Targeted Drug Delivery System (CTDDS) using 36 y (1986-2022) data from various research and review articles. All fig. designed using by BioRender website. vThe colon-targeted drug delivery systems developed for the specific site drug delivery which applied for both local and systemic actions of the drug; since the drug targeted to be release within the colon, the unwanted systemic side effects are reduced along with it. Systemic side effects include organ damage, respiratory diseases and, cardiovascular damage and other illnesses. Colon-targeted drug delivery system used in the treatment of diseases in the colon, including ulcerative colitis, irritable bowel syndrome and colorectal cancer. The benefit of colon-targeted drug delivery besides the reduction of side effects also include protection from premature drug release or burst in the stomach or small intestine before reaching the colon. For the development of drugs with such benefits and advantages, drug delivery systems and approaches have used for Colon targeted drug delivery systems, varying from conventional colon-targeting drug delivery systems to novel approaches for Colon-targeted drug delivery systems. Conventional drug delivery includes the use of prodrugs, pH-dependent, time-dependent, matrix-based systems, polysaccharides-derived systems, and bio-adhesive system while novel approaches include types such as port system, pulsincap system, pressure-controlled system, osmotic controlled system, CODES, and the newest approach wish is the use of nanotechnology in colon targeted drug delivery. In this research both techniques reviewed, and their types discussed as well. The limitation of their uses and the advantage of each system discussed with a breakdown of the different mechanisms used to formulate such systems. A successful colon targeting delivery can release the drug to a specific segment in colon due to presence of different colonic enzymes formed by microorganisms that metabolize drug carrier linkage. Use of combined approaches i.e., conventional systems and newer approaches may be the best way to cure colon diseases using an optimized colon drug delivery system.

Targeted modulation of intestinal epithelial regeneration and immune response in ulcerative colitis using dual-targeting bilirubin nanoparticles.

Rationale: The therapeutic benefits of bilirubin in the treatment of ulcerative colitis (UC) are considerable, whereas the underlying mechanism of bilirubin on UC remains unclear remains unexplored. In addition, the weak hydrophilicity and toxicity have limited its translational applications. Methods: We have developed a colon dual-targeting nanoparticle, for orally delivering bilirubin through hydrogel encapsulation of hyaluronic acid (HA)-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles (HA-PLGABilirubin). Confocal microscopy and in vivo imaging were used to evaluate the uptake and the targeted property of HA-PLGABilirubin in UC. Immunohistochemistry, immunofluorescence, and transcriptomic analyses were applied to examine the therapeutic effect and potential mechanism of HA-PLGABilirubin in UC. Results: Our results indicated that HA-PLGAbilirubin can significantly enhance the release of bilirubin at simulated intestinal pH and demonstrate higher cellular uptake in inflammatory macrophages. Moreover, in vivo biodistribution studies revealed high uptake and retention of HA-PLGAbilirubin in inflamed colon tissue of UC mouse model, resulting in effective recovery of intestinal morphology and barrier function. Importantly, HA-PLGAbilirubin exerted potent therapeutic efficacy against ulcerative colitis through modulating the intestinal epithelial/stem cells regeneration, and the improvement of angiogenesis and inflammation. Furthermore, genome-wide RNA-seq analysis revealed transcriptional reprogramming of immune response genes in colon tissue upon HA-PLGAbilirubin treatment in UC mouse model. Conclusion: Overall, our work provides an efficient colon targeted drug delivery system to potentiate the treatment of ulcerative colitis via modulating intestinal epithelium regeneration and immune response in ulcerative colitis.

Active nanoparticle targeting of MUC5AC ameliorates therapeutic outcome in experimental colitis.

Inflammatory bowel diseases (IBDs), which include Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory diseases of the gastrointestinal tract and are characterized by chronic recurrent ulceration of the bowels. Colon-targeted drug delivery systems (DDS) have received significant attention for their potential to treat IBD by improving the inflamed tissue selectivity. Herein, antiMUC5AC-decorated drug loaded nanoparticles (NP) are suggested for active epithelial targeting and selective adhesion to the inflamed tissue in experimental colitis. NPs conjugated with antiMUC5AC (anti-MUC5) were tested for their degree of bioadhesion with HT29-MTX cells by comparison with non-targeted BSA-NP conjugates. In vivo, the selectivity of bioadhesion and the influence of ligand density in bioadhesion efficiency as well as the therapeutic benefit for glucocorticoid loaded anti-MUC5-NP were studied in a murine colitis model. Quantitative adhesion analyses showed that anti-MUC5-conjugated NP exhibited a much higher binding and selectivity to inflamed tissue compared to PNA-, IgG1- and BSA-NP conjugates used as controls. This bioadhesion efficiency was found to be dependent on the ligand density, present at the NP surface. The binding specificity between anti-MUC5 ligand and inflamed tissues was confirmed by fluorescence imaging. Both anti-MUC5-NP and all other glucocorticoid containing formulations led to a significant mitigation of the experimental colitis, as became evident from the substantial reduction of myeloperoxidase activity and pro-inflammatory cytokine concentrations (TNF-α, IL-1β). Targeted NP by using anti-MUC5 appears to be a very promising tool in future treatment of various types of local disorders affecting the gastro-intestinal tract but not limited to colitis.

Microspheres: A Novel Approach for Sustained Colon Targeted Drug Delivery

Abstract: Colon targeted medication delivery is a field of study for disorders including colon can-cer and inflammatory bowel disease (IBD), with the goal of delivering localised therapy with mini-mal systemic damage. In recent decades, the global prevalence of colonic problems has increased, demanding more local treatment of colonic disorders, which will lead to the development of more effective and safe pharmaceutical regimens. When developing a formulation for colonic administra-tion, it's critical to consider both the physiological characteristics of the colon and the environment surrounding the disease site (s). The GI tract experiences dynamic changes in motility, fluid vol-ume, enzyme activity, and pH from the stomach to the intestine. The current review focuses on Bio-degradable polymers or protein‑based microspheres having free‑flowing properties and particle size 5200 nm have a variety of advantages over conventional colon targeted drug delivery systems. Dur-ing drug transit through the GIT, polysaccharides maintain their integrity and inhibit drug release. When it comes into contact with colonic fluid, however, it is attacked by anaerobic microbes, and the imprisoned medication is released. In this review, several methods of microsphere formulation and characterization were investigated along with its in vitro and in vivo study methodology.

Oral delivery of pectin-chitosan hydrogels entrapping macrophage-targeted curcumin-loaded liposomes for the treatment of ulcerative colitis

The oral delivery of anti-inflammatory drugs has been a promising strategy for enhancing the clinical efficacy of ulcerative colitis (UC) treatment strategies. However, achieving site specific drug delivery to colon tissues and target cells is a challenging task for formulation scientists. In this study, macrophages-targeted liposome-loaded pectin-chitosan hydrogels were developed for UC treatment via oral administration. Folate-functionalized cholesterol was synthesized as lipid membrane materials for the liposomes containing curcumin (CUR). The incorporation of the liposomal CUR within pectin-chitosan hydrogels resulted in a matrix that exhibited considerable sensitivity to colonic enzymes during in vitro release. The targeted delivery of hybrids was able to effectively reach macrophages. They also showed enhanced capability to downregulate TNF-α, IL-6, and IL-1β in the lipopolysaccharide-induced Raw 264.7 cells model. DSS-induced mice modelshowed improved anti-UC effects, including accelerated mucosal repair and decreased inflammation and modulate the immune balance in the intestinal tissue of mice with colitis, which may be attributable to increased drug accumulation in the colonic lumen and improved internalization to target cells. Therefore, the incorporation of folate-modified liposomes containing CUR and pectin-chitosan physical hydrogels could potentially serve as a favorable approach for treating UC through an oral colon-targeted drug delivery system.

QbD: A novel approach for formulation and optimization of colon targeted drug delivery system containing mebeverine HCl

The aim of the work is to study the programmed release of model antispasmodic drug Mebeverine HCl based on pulsatile principle to target colon proximity. Compression coated tablets included core tablet consisting of Croscarmellose as super disintegrant and pulsatile layer comprising impermeable Ethocel cup and mixture of Keltone, Eudragit S100, Ethocel as swellable and rupturable layer. The prepared core tablet was evaluated for weight variation, hardness, thickness, friability, drug content, disintegration time and in vitro dissolution studies. For optimization Box-Behnken design was employed to study the effect of independent variables viz., weight ratio of Keltone (X1), Eudragit S100 (X2), Ethocel (X3) on dependent variables viz., t10 (Y1), t50 (Y2) and Q12 (Y3). Results revealed positive influence of independent factors on responses. The data were statistically analyzed using ANOVA and were found to be statistically significant (P < 0.05). Mathematical modeling for kinetic studies revealed that the release profile after lag time followed first order kinetics. The results concluding that a successful pulsatile drug delivery system of Mebeverine HCl was developed.

Challenges, opportunities, and future prospects of polysaccharide-based nanoparticles for colon targeting: A comprehensive review

Polysaccharides have attracted considerable attention as potential vehicles for drug delivery because of their unique and versatile characteristics. The biodegradability, biocompatibility, mucoadhesive characteristics, and tunable properties of polysaccharide make them attractive carriers for formulating of colon-targeted drug delivery systems. This review article encompasses the research on nanoparticles (NPs) based on polysaccharides (e. g. pectin, sodium alginate and chitosan) for targeted drug delivery to the colon. Various strategies such as microbially triggered, enzymatic degradation, and pH responsive systems have been discussed. Furthermore, ligand-based active targeting of therapeutics to colon has also been highlighted. The review also covers the various characterization and evaluation techniques used in the development of polysaccharide-based NPs. The importance of morphology, particle size (PS), surface charge of the NPs on performance of the delivery system has also been given due consideration. The challenges and future perspectives associated with colon drug delivery have been summarized. The information presented will be helpful to the scientific community when working with polysaccharides and will pave the way for improved therapeutic outcomes.

Fabrication of a Dual-Triggered Natural Gum–Based Multi-Particulate Colon-Targeted Drug Delivery System of Budesonide Using the QbD Approach

Fabrication of a Dual-Triggered Natural Gum–Based Multi-Particulate Colon-Targeted Drug Delivery System of Budesonide Using the QbD Approach

Formulation And In Vitro, In Vivo Evaluation of Colon Targeted Drug Delivery System Of 5-Fluorouracil

Colon-targeted drug delivery systems can provide therapeutic benefits including better patient compliance and lower costs. The present investigation is aimed to design a colon specific microbially triggered system using biodegradable co-polymer mixtures. The calibration curves of 5-FU were measured in distilled water, 0.1N HCl and phosphate buffer of pH 6.8 and 7.4 which showed good linearity. Compatibility study of pure drugs, excipients and their physical mixtures were evaluated and passed as per standards. Solubility determination was carried out in different solvents. Satisfactory results were found from evaluation of micromeritic parameters such as flow property, in-vitro dissolution study and kinetic study. The prime focus of the study was to design and evaluate a swelling dependent delayed release system for a colonic delivery of anticancer agent 5-Fluorouracil (5-FU) and further to determine the effects of carboxy polymer (Carbopol 71G-NF) on release behavior of 5-FU from a matrix tablet system containing different amounts of inulin (a biodegradable oligofructose) aiding in enzymatic degradation by colonic microflora. Mixed film coating with a blend of Ethyl cellulose: Eudragit®S-100 (2:1) at coat weight levels of 2%w/w, 4%w/w and 6.0%w/w was carried out respectively, which further retarded the drug release in the initial hours of the in-vitro dissolution profile. Swelling studies were also carried out on uncoated matrix tablet batches. The releases studies with or without rat cecal contents were performed on optimized batches and the samples were analyzed by a validated RP-HPLC method. In-vitro rat cecal study results revealed that complete drug release would occur from the tablets in the human colonic microenvironment. The study revealed an effective site-specific delivery of a hydrophilic chemotherapeutic agent, 5-FU to the colon for the treatment of various local as well as systemic pathologies.

Formulation and Evaluation of Microspheres for Colon Targeted Drug Delivery Using Anthelminthics Drugs

The objective of this study was to develop sustained release microspheres for colon-targeted drug delivery system to enhance therapeutic efficacy while minimizing systemic side effects. The controlled and prolonged release of drugs in the colon can significantly improve the treatment outcomes for various colon-related diseases. Microspheres, small spherical particles with sizes ranging from 1 to 1000 micrometers, were formulated using biodegradable polymers and natural materials to ensure biocompatibility and controlled drug release. The formulation process involved the selection of appropriate polymers, such as poly lactic acid and polyglycolic acid, and the incorporation of the drug within the microspheres. Various techniques, including solvent evaporation, coacervation, and spray drying, were employed to prepare the microspheres with the desired drug-loading efficiency and particle size distribution.The formulated microspheres were extensively evaluated to assess their suitability for sustained release colon-targeted drug delivery. Evaluation parameters included drug encapsulation efficiency, particle size distribution, surface morphology and in vitro.In vitro drug release studies were conducted using simulated gastrointestinal fluids to mimic the conditions in the gastrointestinal tract. The sustained release microspheres exhibited controlled drug release over an extended period, specifically in the colon region. This sustained release profile was achieved by optimizing the polymer composition and formulation parameters, which allowed for the gradual degradation of the microspheres and subsequent release of the drug.

Rapid Indomethacin Release from Porous Pectin Particles as a Colon-Targeted Drug Delivery System.

The conventional pectin delivery systems in the colon are often impaired by a slow release rate. Nanostructured particles, especially porous ones, have gained popularity as drug delivery systems owing to their high mass transfer efficiency. In this research, porous pectin particles were synthesized as drug carriers (using indomethacin as a model drug) via template-assisted spray drying. Specific surface areas of the porous pectin particles have been improved by up to 203 m2 g-1 compared with nonporous particles (1 m2 g-1). The porous structure shortened the diffusion path and improved the release rate of drug molecules. Additionally, the predominant drug release mechanism from porous pectin particles is Fickian diffusion, which is different from the combination of erosion and diffusion mechanism observed for nonporous particles. As a result, these porous drug-loaded pectin particles demonstrated rapid drug release rates of up to three times faster than nonporous particles. Control of the release rate could be achieved by changing the porous structure of the particles. This strategy is an efficient means to synthesize porous particles allowing rapid drug release into the colonic target.

Formulation Development and Characterization of Vancomycin Hydrochloride Colon-Targeted Tablets Using In-Situ Polyelectrolyte Complexation Technique

Introduction: Vancomycin hydrochloride (VH) is an amphoteric glycopeptide antibiotic used to manage enterocolitis and pseudomembranous colitis. However, VH is prone to proteolytic degradation in the stomach, thus obscuring the drug entry into the colon. Colon-targeted drug delivery can prevent gastric degradation and localise the drug in the colon. 
 Methodology: The applicability of in situ polyelectrolyte complexation technique using the polymers Chitosan, Karaya gum, and Hupu gum at various concentrations along with enteric coating using Eudragit S100 was studied for the preparation of colon-targeted tablets of VH.
 Colon-targeted tablets of VH are developed by incorporating natural polymers like chitosan, karaya gum, and hupu gum at different concentrations such that in-situ polyelectrolyte complex is formed and the formulations were then coated with Eudragit S100(6%, 8%, and 10% weight gain) to release the drug in a controlled manner in the colon. 
 Results: Prepared formulations were subjected to in vitro, ex vivo, and in vivo evaluation studies. Out of all the prepared formulations, the formulation H2C10 prepared with 10:2 PEC and 10% Eudragit S100 coating has shown a sufficient lag time of 2 hours in 0.1N HCl, 3 hours of lag time in pH 6.8 phosphate buffer and has shown a 100.02% drug release at 22 hours in pH 7.4 phosphate buffer. 
 Conclusion: The research results suggested that a colon-targeted drug delivery system of VH can decrease drug degradation and achieve higher concentrations in the colon to provide more therapeutic benefits.

Synthesis of pH-sensitive nanocarrier-based acrylic acid-grafted-flaxseed gum for quercetin delivery for anti-cancer application

This study deals with the fabrication and characterization of quercetin-loaded acrylic acid-grafted-flaxseed gum nanoparticles (QUR@AA-g-FGS) to delivers quercetin to the targeted colonic area and to enhances anti-cancer activity. The acrylic acid-grafted-flaxseed gum (AA-g-FGS) was synthesized using ceric ammonium nitrate (CAN) as a redox initiator via the conventional method. The synthesized acrylic acid-grafted-flaxseed (AA-g-FGS) gum was also optimized through varying grafting parameters such as acrylic acid and CAN concentration, time and temperature to obtain the maximum yield of acrylic acid-grafted-flaxseed gum. The quercetin release behavior of QUR@AA-g-FGS was studied at several biological pH and the highest drug release (95%) was observed at pH 7.4 and 8 h. The quercetin release kinetic data was following the first order (R2 = 0.9842) kinetic model. The cytotoxicity of QUR@AA-g-FGS was investigated on HCT-15 cell line (cancerous human cell line) and, QUR@AA-g-FGS demonstrated outstanding toxicity toward HCT-15 cell line. Thus, the present study procures a worthwhile, nominal and ecologically sound approach toward the synthesis of QUR@AA-g-FGS for colon targeted drug delivery system.

Formulation and Evaluation of Microspheres as an effective Colon Targeting Drug Delivery System

The present work comprised of the preparation of coated HPMC capsules of meloxicam microspheres in order to target the drug release in colon resulting in increased absorption and subsequent bioavailability. The meloxicam microspheres were developed in nineteen different batches using HPMC, combination of EC with HPMC, Eudragits (S100, RS100 and E100) in different drug and polymer ratios by solvent evaporation method. The formulation of different batches were examined by various studies i.e. percentage yield, surface morphology (SEM), particle size analysis, entrapment efficiency, drug compatibility with polymers using FTIR and in-vitro drug release determinations. The complex of meloxicam with β-cyclodextrin increased the solubility of the drug accompanying its in-vitro release. The microspheres filled HPMC capsules were coated with eudragit S100 which proved to be an effective method for drug targeting to the colon. A 22 factorial design showed that a very significant increase in release of the drug using polymers i.e. HPMC, E.C with HPMC, Eudragit S100, Eudragit RS100, Eudragit E100 could be obtained by the exclusive manipulation of two variables i.e. surfactant and polymer concentrations. The drug loaded microspheres showed percentage drug entrapment as 35.09-62.50% in A1-A4, 76.29-87.78% in B1-B4, 81.36-92.70% in S1-S4, 65.47-69.4% in RS1-RS4 and 68.91-78.08% in E1-E3. The pH 7.4 phosphate buffer and simulated colonic fluid were used for the in-vitro release tests. The best drug release profiles were seen with formulations A3, B2, RS1, S1 and E2 (containing different ratios of drug: polymer) coated with 15% (w/v) Eudragit S-100 solution.

Nanotechnology Approaches for Colon Targeted Drug Delivery System: A Review

Debgopal Ganguly1, Ananta Choudhury1 and Subhabrota Majumdar2 Author informationArticle notesCopyright and License information 1Faculty of Pharmaceutical Science, Assam Down Town University, Sankar Madhab Path, Gandhi Nagar, Panikhaiti, Guwahati, Assam, INDIA 2Department of Pharmaceutics, Calcutta Institute of Pharmaceutical Technology and Allied Health Science, Uluberia, Howrah, West Bengal, INDIA Corresponding author. Correspondence: Prof. Ananta Choudhury Assam Down

Hyaluronic acid modified oral drug delivery system with mucoadhesiveness and macrophage-targeting for colitis treatment

Based on the biocompatibility and macrophage targeting of natural polysaccharides, combined with the physiological and pathological characteristics of the gastrointestinal tract and colonic mucosa of ulcerative colitis (UC), we prepare dexamethasone (Dex)-loaded oral colon-targeted nano-in-micro drug delivery systems coated with multilayers of chitosan (CS), hyaluronic acid (HA), and finally Eudragit S100 (ECHCD MPs) using a layer-by-layer coating technique for UC treatment through regulating the M1/M2 polarization of intestinal macrophages. HA/CS/Dex nanoparticles (HCD NPs) are ingested by macrophages via CD44 receptor-mediated endocytosis to regulate M1-to-M2 macrophage polarization and exert anti-inflammatory effects. Moreover, ECHCD MPs show better colon-targeting properties than Dex-loaded chitosan nanoparticles (CD NPs) and HCD NPs which is demonstrated by stronger mucoadhesion to inflamed colon tissues. After oral administration, ECHCD MPs exert significant anti-UC effects. Therefore, ECHCD MPs are proven to be as promising oral colon-targeting drug delivery systems for Dex and have potential application in UC treatment.

A Review on Colon Targeted Drug Delivery System

Colon-specific drug delivery systems (CDDS) are advantageous for the treatment of a range of local diseases such as ulcerative colitis, Crohn’s disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. Colon targeted drug delivery system can be utilized to deliver protein and peptide drugs as they that are known to degrade in the extreme gastric pH. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the variation in the pH along the GI tract, the occurrence of colonic microflora, and enzymes, to attain colon targeting. This article highlights the advantages, limitations and factors influencing colon-specific drug delivery. Further, the review gives information of various conventional, as well as relatively newer formulation approaches presently being utilized for the improvement of CDDS.