Colon Targeted Drug Delivery System Research Articles

Preparation and characterization of copper oxide-chitosan nanocomposite for colon-targeted drug delivery system

Preparation and characterization of copper oxide-chitosan nanocomposite for colon-targeted drug delivery system

A Comprehensive Review of Challenges in Oral Drug Delivery Systems and Recent Advancements in Innovative Design Strategies.

The oral route of drug administration is often preferred by patients and healthcare providers due to its convenience, ease of use, non-invasiveness, and patient acceptance. However, traditional oral dosage forms have several limitations, including low bioavailability, limited drug loading capacity, and stability and storage issues, particularly with solutions and suspensions. Over the years, researchers have dedicated considerable effort to developing novel oral drug delivery systems to overcome these limitations. This review discusses various challenges associated with oral drug delivery systems, including biological, pharmaceutical, and physicochemical barriers. It also explores common delivery approaches, such as gastroretentive drug delivery, small intestine drug delivery, and colon-targeting drug delivery systems. Additionally, numerous strategies aimed at improving oral drug delivery efficiency are reviewed, including solid dispersion, absorption enhancers, lipidbased formulations, nanoparticles, polymer-based nanocarriers, liposomal formulations, microencapsulation, and micellar formulations. Furthermore, innovative approaches like orally disintegrating tablets (ODT), orally disintegrating films (ODF), layered tablets, micro particulates, self-nano emulsifying formulations (SNEF), and controlled release dosage forms are explored for their potential in enhancing oral drug delivery efficiency and promoting patients' compliance. Overall, this review highlights significant progress in addressing challenges in the pharmaceutical industry and clinical settings, offering novel approaches for the development of effective oral drug delivery systems.

Emerging Nanoparticle-Based Herbal Drug Delivery Systems for Colon Targeting Therapy

Abstract: Herbal medications hold a dominant position in the pharmaceutical sector due to their well-established therapeutic effects and extremely low negative effects. Besides, herbal remedies are easily available and highly economical. However, to circumvent the issue of poor bioavailability, the combinatorial strategy of incorporating herbal medicines and nano-technology is useful. The phytoconstituents molded in novel nanocarriers such as polymeric nanoparticles, polymeric micelles, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, gold nanoparticles, etc., have been extensively investigated as they are the most promising approach for colon-targeting drug delivery systems. Although plant-based medicines have been developed for decades, there is enormous research interest in the development of an effective plant-derived delivery system for the incorporation of phytocon-stituents into various nanomaterials to overcome potential challenges related to solubility, bioavailability, and stability issues. The encapsulation of phytoconstituents in a novel nanocarrier is a promising approach to improving the bioavailability, stability, and therapeutic efficacy of herbal medicines. The herbal nanomedicines are used as a promising tool for tar-geted delivery to the colon, with potentially effective outcomes for the treatment of colonic diseases, viz., ulcerative colitis, diverticulitis, Crohn's disease, shigellosis, constipation, co-lonic polyps, colon cancer, etc. This article presents a comprehensive survey of recent find-ings and patents by innovators working exclusively on nanoparticles for the delivery of phy-tomedicines for colon targeting.

Advances in Colon-Targeted Drug Delivery Systems: Innovative Strategies for Treating Colonic Disorders and Prospects for the Future.

Colon-specific targeting delivery systems have drawn a great deal of attention because they represent potential vehicles for treating colonic disorders like diverticulitis, colitis, salmonellosis, Crohn's disease, etc. with less systemic adverse effects as well as for the better oral delivery of many therapeutics that are prone to enzymatic and acidic deterioration in the upper GI tract. Smart polymeric delivery systems in particular have been investigated as "intelligent" delivery systems capable of releasing entrapped pharmaceuticals at the proper time & site of action in response to certain physiological stimuli. The creation of novel polymers & crosslinkers with improved biodegradability and biocompatibility would expand and enhance applications now in use. The development of polymeric systems could result in more precise and programmable drug delivery/therapies. In addition, newer advancements have led to the development of numerous ground-breaking techniques for directing a medication molecule to the colon. This review highlighted formulation techniques pH-dependent, time-dependent, enzyme sensitive, magnetically dependent, ligand-receptor mediated, and microflora-activated systems. Moreover, several methods have been put forth that make use of the innovative idea of such delivery systems, and mechanisms in which the release of drugs is regulated by pH and time as well as pH and the colon's bacteria.

Chitosan-melanin complex microsphere: A potential colonic delivery system for protein drugs

The characteristics and performance of chitosan-based colon delivery systems are significantly influenced by the method of preparation. Insect chitosan-melanin complex (CMC) may offer superior attributes over traditional shrimp and crab chitosan (CS) for colon-targeted administration. This study used dung beetle CMC as the carrier matrix and comprehensively examined the impact of various crosslinking techniques on the colonic drug delivery efficacy of microspheres, encompassing drug loading, swelling, drug release behavior, adhesion, enzymatic degradation, and absorption enhancement. The results indicate that F-TPPLC microspheres, crosslinked with a combination of formaldehyde and TPP, exhibit superior drug loading capabilities, optimal swelling behavior, and controlled in vitro drug release profiles in the colonic environment, along with excellent adhesion and enzymatic degradation properties within intestinal tract. Notably, these F-TPPLC microspheres increase paracellular permeability, possibly by disrupting the calcium-dependent adhesion junctions. In comparison to commercial CS, CMC demonstrates superior drug encapsulation efficiency, enhanced colonic drug release, adhesion, and absorption promotion, rendering it a favorable candidate as a carrier in colon-targeted drug delivery systems. Consequently, F-TPPLC microspheres derived from CMC are highly suitable for colon drug delivery applications and show promising potential for the oral delivery of peptide and protein-based therapeutics to the colon.

Combining Gut Microbiota Modulation and Enzymatic-Triggered Colonic Delivery by Prebiotic Nanoparticles Improves Mouse Colitis Therapy.

The efficacy of ulcerative colitis (UC) therapy is closely connected to the composition of gut microbiota in the gastrointestinal tract. Prebiotic-based nanoparticles (NPs) provide a more precise approach to alleviate UC via modulating gut microbiota dysbiosis. The present study develops an efficient prebiotic-based colon-targeted drug delivery system (PCDDS) by using prebiotic pectin (Pcn) and chitosan (Csn) polysaccharides as a prebiotic shell, with the anti-inflammatory drug sulfasalazine (SAS) loaded into a poly(lactic-co-glycolic acid) (PLGA) core to construct SAS@PLGA-Csn-Pcn NPs. Then, we examine its characterization, cellular uptake, and invivo therapeutic efficacy. The results of our study indicate that the Pcn/Csn shell confers efficient pH-sensitivity properties. The gut microbiota-secreted pectinase serves as the trigger agent for Pcn/Csn shell degradation, and the resulting Pcn oligosaccharides possess a substantial prebiotic property. Meanwhile, the formed PCDDSs exhibit robust biodistribution and accumulation in the colon tissue, rapid cellular uptake, efficient invivo therapeutic efficacy, and modulation of gut microbiota dysbiosis in a mouse colitis model. Collectively, our synthetic PCDDSs demonstrate a promising and synergistic strategy for UC therapy.

Review on Colon Targeted Drug Delivery System

This review focuses on the importance of local drug delivery in the treatment of Gastro intestinal diseases ulcerative colitis, Crohn’s disease, amebiasis, colon cancer. For many types of drugs, oral administration is the most common route of administration due to patient compliance and flexibility. Targeted drug delivery system is a system that sends drugs to diseased areas by changing the amount of information. The large intestine is where local drug delivery and systemic diseases can occur. Treatment will be better if the drug directly targets the intestine. The large intestine is where the local child allows local treatment of intestinal diseases and the distribution of drugs. Gastrointestinal therapeutic drugs are effective when they can be directly targeted to the intestine, because drug release and absorption should not occur in the stomach and small intestine and the bioactive agents should not be broken down and released into the intestine. Drugs targeting the intestinal area not only affect the treatment of local diseases, but also deliver drugs such as proteins and peptides to the body due to their effects on the body. At the same time, due to weakness of the digestive system, these drugs are broken down and their availability is quiet low.

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.

Current Update of Clinical Therapeutic Strategies for Colon-Targeted Delivery Systems

Oral colon-targeted drug delivery systems represent a significant advancement offering both systemic and local therapeutic effects for a range of intestinal diseases, including irritable bowel syndrome, inflammatory bowel disease, colonic bacterial infections, and colorectal cancer. These systems facilitate the delivery of both small molecules and macromolecular compounds such as peptides, proteins, antibodies, oligonucleotides, RNA, and probiotics. This review provides an up-to-date exploration of the critical factors crucial for the effective design and development of drug delivery systems targeting the colon. The chosen strategy takes into account various aspects of colon physiology that influences the profile of drug release, absorption, dissolution, and stability in the colon, including pH, retention time, presence of enzymes, pressure, presence of reactive oxygen species due to inflammation, and specific receptors. Site-targeted drug release allows for high concentrations in the colon while minimizing systemic adverse effects by reducing or preventing drug absorption in the small intestine.

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.