Colon Targeted Drug Delivery Research Articles

A Research on Gauging of Colon Targeted Drug Delivery of Loperamide HCL with Pectin-Bora Rice Microsphere

A Research on Gauging of Colon Targeted Drug Delivery of Loperamide HCL with Pectin-Bora Rice Microsphere

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.

Engineered Shellac Beads-on-the-String Fibers Using Triaxial Electrospinning for Improved Colon-Targeted Drug Delivery.

Colon-targeted drug delivery is gradually attracting attention because it can effectively treat colon diseases. Furthermore, electrospun fibers have great potential application value in the field of drug delivery because of their unique external shape and internal structure. In this study, a core layer of hydrophilic polyethylene oxide (PEO) and the anti-colon-cancer drug curcumin (CUR), a middle layer of ethanol, and a sheath layer of the natural pH-sensitive biomaterial shellac were used in a modified triaxial electrospinning process to prepare beads-on-the-string (BOTS) microfibers. A series of characterizations were carried out on the obtained fibers to verify the process-shape/structure-application relationship. The results of scanning electron microscopy and transmission electron microscopy indicated a BOTS shape and core-sheath structure. X-ray diffraction results indicated that the drug in the fibers was in an amorphous form. Infrared spectroscopy revealed the good compatibility of the components in the fibers. In vitro drug release revealed that the BOTS microfibers provide colon-targeted drug delivery and zero-order drug release. Compared to linear cylindrical microfibers, the obtained BOTS microfibers can prevent the leakage of drugs in simulated gastric fluid, and they provide zero-order release in simulated intestinal fluid because the beads in BOTS microfibers can act as drug reservoirs.

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.

Colon Target Drug Delivery System Review

For the local treatment of a number of bowel disorders such as ulcerative colitis, Crohn's disease, amoebiasis and sand, colonic cancer, the local treatment of colonic pathologies, and the systemic distribution of protein and peptide medicines, targeted drug delivery into the colon is extremely desirable. A medication must be properly formulated for colon-focused drug delivery. To ensure sudden or controlled release in the proximal colon, the substance must first be shielded from degradation, release, and absorption in the upper GI tract. The advantages and disadvantages, cutting-edge methods for colon-targeted drug delivery, clinical evaluation methods, and some details about commercial dosage forms are the main topics of this paper

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.

A critical review on formulation and evaluation of colon targeted drug delivery systems

A multidisciplinary scientific field that is fast growing is nanotechnology, often known as molecularly generated systems and technologies. Nanotechnology is a rapidly expanding field of applied science and engineering. It relies upon the concept of nano-scale manipulation of matter, meaning the ability to handle materials on a microscopic scale. Nanoparticles can be used to deliver a variety of substances, including conventional drugs, recombinant proteins, vaccines, and more recently nucleotides. Nanoparticles and other colloidal drug delivery techniques change the kinetics, body distribution, and drug release of a related drug. The treatment of negative effects and the distribution of therapy that targets certain tissues or cells are additional effects. As a result, nanoparticles in the pharmaceutical and biotechnology industries boost the therapeutic index and provide solutions to impending delivery problems for new classes of so-called biotech medicines such recombinant proteins and oligonucleotides.

Development of a modified hard gelatin capsule for colon-targeted drug delivery of hydrogel-based piroxicam microparticles

Purpose: To develop modified hard gelatin capsules (MHGCs) for colon-specific delivery of hydrogel-based piroxicam microparticles.
 Methods: Solvent evaporation technique was adopted for the microencapsulation of piroxicam using liquid paraffin (PL.MPs) and soybean oil (PS.MPs) which were subsequently encapsulated in MHGCs (water-impervious). Anti-inflammatory and in vitro dissolution studies were conducted on the unencapsulated microparticles (MPs). Furthermore, in vitro colon-specific sequential drug release from impervious capsules was carried out for 2 h at pH 1.2 and 3 h in 6.8, and ≥ 5 h in 7.4, to simulate drug release in the stomach, small intestine, and colon environment, respectively. Differential scanning calorimetry (DSC) analysis was also conducted on the formulations.
 Results: Edema inhibition of PL.MPs and PS.MPs were within the range of 51.0 – 64.0 and 58.0 – 69.0 %, respectively. In vitro colon-specific drug dissolution studies revealed absence, minimal, and highest amounts of drug release from MHGCs in pH 1.2, 6.8 and 7.4 media, respectively. Decreased crystallinity of the microparticles was indicated by a broad endothermic peak.
 Conclusion: The MHGCs hold promise as a potential alternative delivery system for hydrogel-based piroxicam microparticles designed for colon-targeted drug delivery. However, clinical development studies are required.

Development of Polyelectrolyte Complex Beads Containing Vancomycin Hydrochloride for Colon-targeted Drug Delivery

Development of Polyelectrolyte Complex Beads Containing Vancomycin Hydrochloride for Colon-targeted Drug Delivery

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.

Formulation and evaluation of 5-fluorouracil controlled release chronotherapeutic drug delivery system (CTDDS) for colorectal cancer

Objective: As most of the drugs disintegrate and dissolve in stomach before reaching the target site and to substitute intravenous (IV) route based chrono modulated chemotherapy, oral colon target drug delivery system was formed. The aim of this study was to design, develop, and evaluate a colon targeted tablet containing 5-Fluorouracil (5-FU) to give a controlled release effect of drug for colonic cancer with a goal to increase the bioavailability and improve the patient compliance. Methods: Varied concentration of different polymers such as Xanthan gum and Eudragit were used to get an optimized formulation of 5-FU tablet. The prepared formulation was evaluated for pre compression and post compression parameters such as hardness, weight, friability and drug content uniformity. The optimized formulation was further evaluated by Fourier Transformed Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), in-vitro dissolution studies, dissolution kinetic modeling and stability analysis. Results: All pre-formulation tests were within range of USP standards. Friability of all tablets was satisfied. The interference of the polymers was ruled out by FTIR. In-vitro release studies of 5-FU tablets in phosphate buffer of pH 7.0 were performed using a modified diffusion cell that resulted sustained release (90.99% to 92.69% after 12h) and kinetic models depicted the combined diffusion and dissolution mechanism of release. The optimized tablets were found having only physical interactions based on DSC. The product was found stable when evaluated using accelerated stability studies. Conclusion: It was concluded from the studies that the colon target tablet of 5-FU prepared by different concentration of polymers were optimized and can be efficiently used to control the rate of drug release to the colon in the belief of improved therapeutic efficacy and tolerability. Therefore, it is a better alternative for intravenous route based chrono modulated chemotherapy.

Formulation of Pectin-Based Double Layer-Coated Tablets Containing Dexamethasone and Probiotics for Inflammatory Bowel Disease

Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition in the colon that includes ulcerative colitis and Crohn’s disease. Dexamethasone is a steroid anti-inflammatory drug that can be used in IBD therapy. This study aims to obtain an optimum formulation of a dexamethasone drug delivery system for IBD treatment and to investigate its release profile based on an in vitro dissolution test. Dexamethasone was formulated as a double-coated tablet in combination with a probiotic L. acidophilus and B. longum mixture (1:1). The core tablets were produced using the wet granulation method, after which they were coated with pectin 4% b/v on the inner coat and a mixture of Eudragit L100 and S100 (1:4) on the outer coat. Three different core tablet formulas were prepared by varying the concentration of probiotics at 0%, 16% and 40% (F1, F2, and F3, respectively). The cumulative drug release of F1, F2 and F3 in HCl 0.1 N pH 1.2 for 2 hours were 42.92 ± 1.55%, 39.41 ± 4.10%, and 39.39 ± 1.63%, respectively, while in the phosphate buffer pH 6.8 they were 102.83 ± 1.56%, 105.08 ± 1.70%, and 98.81 ± 3.37% respectively, after 12 hours. From the results, we conclude that all formulas could be promising candidates for developing colon-targeted drug delivery.

Preparation and in vitro evaluation of hot-melt extruded pectin-based pellets containing ketoprofen for colon targeting

This work developed high drug-load pellets for colon targeting in minimal steps by coupling hot-melt extrusion (HME) with a die-surface cutting pelletizer, offering a potential continuous pellet manufacturing process. Ketoprofen (KTP) was selected as a model drug for this study due to its thermal stability and severe upper gastrointestinal side effects. Low and high methoxyl grade pectins were the enzyme-triggered release matrix, and hydroxypropyl methylcellulose (HME 4 M/HME 100LV) was used as a premature release-retarding agent. The powder X-ray diffraction technique and the differential scanning calorimetry results revealed that KTP exists in the solid-solution state within the polymeric matrix after the HME step. The scanning electron micrographs of the fabricated pellets showed a smooth surface without any cracks. The lead formulation showed the lowest premature drug release (∼13%) with an extended KTP release profile over a 24 h period in the presence and absence of the release-triggering enzyme. The lead formulation was stable for 3 months at accelerated stability conditions (40 °C/75 ± 5% RH) concerning drug content, in vitro release, and thermal characteristics. In summary, coupling HME and pelletization processes could be a promising technology for developing colon-targeted drug delivery systems.

Novel Approaches For Colon Site-Specific Drug Delivery: An Overview Of Recent Advancements

Nowadays, various routes of administration have been explored for the effective delivery of the drug to the target site. The oral route is considered to be the most convenient for the administration of drugs to patients. But it has a serious drawback in conditions where localized delivery of the drug in the colon is required. The colon-targeted drug delivery system (CDDS) is a potential approach for systemic and topical drug delivery in treating inflammatory bowel diseases such as ulcerative colitis, Crohn’s disease, colon cancer, and amoebiasis. CDDS would provide direct treatment at the site of the disease, reduced dose, and reduced systemic adverse effects. CDDS should be able to release the drug into the colon, indicating that neither drug release nor absorption should take place in the stomach or small intestine, nor should the bioactive agent be degraded there. Instead, the drug should only be released and absorbed when it reaches the colon. The colon is a site for both local and systemic drug delivery. This review mainly compares the primary approaches for CDDS (Colon Specific Drug Delivery) namely prodrugs, pH and time-dependent systems, and microbially triggered systems, which achieved limited success and had limitations as compared with newer CDDS namely pressure-controlled colonic delivery capsules, CODESTM, and osmotic controlled drug delivery systems. The review is also focused on the possible benefits and issues associated with the novel colon-targeted drug delivery system. Recent advancements in various approaches for designing colon-targeted drug delivery systems and their pharmaceutical applications are covered with a particular emphasis on formulation technologies.

Advancement in Therapeutic Intervention of Prebiotic-Based Nanoparticles for Colonic Diseases.

Intestinal flora has become a therapeutic target for the intervention of colonic diseases (CDs) with better understanding of the interplay between microbiota and CDs. Depending on unique properties and prominent ability of regulating the intestinal flora, prebiotics can not only achieve a colon-specific drug delivery but also maintain the intestinal homeostasis, thus playing a positive role in the intervention of CDs. Currently, different studies on prebiotic-based nanoparticles have been contrived for colonic drug delivery and have shown great potential in curing various CDs, such as colitis and colorectal cancer. Nevertheless, there is a lack of systematic survey on the use of prebiotic nanoparticles for the treatment of CDs. This review aims to generalize the state-of-the-art of prebiotic nanomedicines specific for CDs. The species and function of intestinal flora and various kinds of prebiotics available as well as their regulating effects on intestinal flora were expounded. A variety of prebiotic nanoparticles pertinent to colon-targeted drug delivery systems were illustrated with particular emphasis on their curative activities on CDs. The efficacy and safety of prebiotic-based colonic drug delivery systems (p-CDDs) were also analyzed. In conclusion, the synergy between prebiotic nanoparticles and their cargos may hold promise for the treatment and intervention of CDs.

Designing robust xylan/chitosan composite shells around drug-loaded MSNs: Stability in upper GIT and degradation in the colon microbiota

Long residence times, near-neutral pH values, and release triggered by the enzymatic action of the resident microbiota offer unique opportunities for improved drug delivery in the colon. The fact that a delivery agent must also pass through the complete GI tract without degradation presents a challenge due to widely changing pH conditions. In this study, a promising colon-targeted drug delivery system was composed of a xylan/chitosan composite shell formed on curcumin-loaded mesoporous silica nanoparticles (MSNs). A novel synthesis approach was employed to facilitate precipitation of negatively charged xylan on negatively charged MSNs by concurrent chitosan polymerization. Curcumin-loaded xylan/chitosan-coated MSNs (C-MSNs) were determined to contain nearly 42% xylan by the inclusion of chitosan in a one-to-one ratio with xylan. The xylan/chitosan composite shell demonstrated excellent stability in the acidic upper GI tract. The hydrolysis of glycosidic bonds by resident microbiota was the triggering mechanism for xylan degradation and curcumin release in the colon. The presence of xylan has the further benefit of increasing the number of beneficial bacteria and improving short-chain fatty acid production for improved colon health.

An oral delivery vehicle based on konjac glucomannan acetate targeting the colon for inflammatory bowel disease therapy.

Orally administered colon-targeted delivery vehicles are of major importance in the treatment of inflammatory bowel disease (IBD). However, it remains a challenge to maintain the integrity of such delivery vehicles during treatment, particularly in the gastric environment, which may cause untimely drug release before reaching the targeted colon. Herein, an oral colon-targeted drug delivery system (OCDDS) based on acetylated konjac glucomannan (AceKGM) has been developed in this work, which accomplishes colonic localization release and targets local inflammatory macrophages. The AceKGM nanoparticle-loading curcumin (Cur) was successfully fabricated by emulsion solvent evaporation techniques. DLS, AFM, and SEM were used in order to evaluate the nanoparticles' diameter as well as their in vitro drug release profile, and reactive oxygen species (ROS) scavenging results showed that the OCDDS considerably retained the activity of Cur treated with simulated gastric fluid (SGF) and controllably released in simulated intestinal fluid (SIF). In addition, the adhesion experiment results indicated that the nanoparticle could accumulate on the colonic macrophages. Evaluations in colitis mice showed that the treatment significantly alleviated the symptoms of colitis by decreasing the local level of myeloperoxidase (MPO) and the disease activity index (DAI) score in mice. In summary, the results of our research demonstrate that Cur-AceKGM nanoparticles exhibit significantly improved therapeutic efficacy compared to orally administered free Cur and can be developed as an effective drug delivery vehicle for IBD treatment.

Colon targeted drug delivery systems: Based on Polymers

Research on colon-targeted polymers delivery systems is ongoing for conditions such ulcerative colitis, Crohn's disease, colon cancer, as well as the delivery of peptide or protein medications and vaccines. For colon-specific disorders in particular, focused nano-drug delivery to the colon is helpful because nanoparticles can build up in sick areas, improve therapeutic efficacies, and allow localized therapies, which lower systemic toxicity. The efficient delivery of NDDS to the colon, however, may be hampered by a number of obstacles, including burst drug release, enzyme and acidic degradation of drug and carrier in the stomach, pH fluctuations, mucus trapping, and systemic uptake in the upper small intestine. These obstacles might be surmounted with improvements in NDDS, resulting in effective drug delivery for colon-specific illnesses. This review provides an updated summary of recent advances in the development of orally administered NDDS for colon targeting and the future advancements in this research. It also discusses some potential colon-specific drug delivery areas, challenges faced by colon-targeted oral delivery systems, and potential drug delivery areas.