Colon-specific Delivery Research Articles

Colon-specific delivery of methotrexate using hyaluronic acid modified pH-responsive nanocarrier for the therapy of colitis in mice

Oral immunosuppressant methotrexate (MTX) is an effective method for the treatment of inflammatory bowel disease (IBD). To overcome the defects of clinical application of MTX, poly (lactic-co-glycolic acid) (PLGA), Eudragits® S100 (ES100), chitosan (CS) and hyaluronic acid (HA) were used to structure the MTX-loaded HA-CS/ES100/PLGA nanoparticles (MTX@hCEP). MTX@hCEP had a hydrodynamic particle size of approximately 202.5 nm, narrow size distribution, negative zeta potential (-18.7 mV), and smooth surface morphology. In vitro drug release experiments under simulated gastrointestinal conditions indicated that MTX@hCEP exhibited colonic pH-sensitive drug release properties. The cellular uptake capacity of hCEP nanoparticles was significantly enhanced in RAW 264.7 macrophages. Moreover, we further found that the MTX@hCEP also inhibited the proliferation and the secretion of pro-inflammatory cytokines in the LPS-stimulated macrophages. In vivo imaging results not only demonstrated that the accumulated in the colon of colitis mice, but also indicated the extended retention time of MTX in the colon. Additionally, MTX@hCEP alleviated inflammatory symptoms via decreasing the activities of myeloperoxidase and pro-inflammatory factors, promoting mucosal repair in vivo. Collectively, these results clearly demonstrated that MTX@hCEP with properties of colon-specific and macrophages targeting can be exploited as an efficient nanotherapeutic for IBD therapy.

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.

Preparation and Characterization of a Novel Multiparticulate Dosage Form Carrying Budesonide-Loaded Chitosan Nanoparticles to Enhance the Efficiency of Pellets in the Colon.

An attempt was made to conquer the limitation of orally administered nanoparticles for the delivery of budesonide to the colon. The ionic gelation technique was used to load budesonide on chitosan nanoparticles. The nanoparticles were investigated in terms of size, zeta potential, encapsulation efficiency, shape and drug release. Then, nanoparticles were pelletized using the extrusion-spheronization method and were investigated for their size, mechanical properties, and drug release. Pellets were subsequently coated with a polymeric solution composed of two enteric (eudragit L and S) and time-dependent polymers (eudragit RS) for colon-specific delivery. All formulations were examined for their anti-inflammatory effect in rats with induced colitis and the relapse of the colitis after discontinuation of treatment was also followed. The size of nanoparticles ranged between 288 ± 7.5 and 566 ± 7.7 nm and zeta potential verified their positive charged surface. The drug release from nanoparticles showed an initial burst release followed by a continuous release. Pelletized nanoparticles showed proper mechanical properties and faster drug release in acidic pH compared with alkaline pH. It was interesting to note that pelletized budesonide nanoparticles released the drug throughout the GIT in a sustained fashion, and had long-lasting anti-inflammatory effects while rapid relapse was observed for those treated with conventional budesonide pellets. It seems that there is a synergistic effect of nanoformulation of budesonide and the encapsulation of pelletized nanoparticles in a proper coating system for colon delivery that could result in a significant and long-lasting anti-inflammatory effect.

Carboxymethyl cellulose based sustainable hydrogel for colon-specific delivery of gentamicin

The current research includes the synthesis, improvement of NaCMC-cl-DMAA/AAc hydrogel and in-situ controlled release of gentamicin within various pH environments. The prepared hydrogel was then modified using boron nitride nanosheets aiming to enhancement in the adsorption rate. The prepared hydrogels were investigated by FTIR, XRD, FESEM, TGA/DSC, swelling and cell viability analysis. Cytotoxicity study indicated that prepared sample has a cytocompatibility nature towards healthy normal human cell line (FR2 cells). By changing the pH environment, the drug release properties of the hydrogels can be controlled. The cumulative rate of release for NaCMC-cl-DMAA/AAc hydrogel was 76.5 % at pH = 2.2 and 87.5 % at pH = 7.4. Whereas drug release rate for NaCMC-cl-DMAA/AAc-BNNSs hydrogel composite was 78.6 % at pH = 2.2 and 97.3 % at pH = 7.4 within 4320 min. Gentamicin release kinetics have been determined using the Korsemeyar-Peppas model, which confirms the drug release mechanism.

Encapsulation of Marjoram Phenolic Compounds Using Chitosan to Improve Its Colon Delivery.

In this study, chitosan particles were used to encapsulate marjoram phenolic compounds as colon-specific drug-delivery systems. The microparticles were prepared by ionic gelation and spray-drying techniques and varying amounts of polymer and extract, along with different method conditions. The spray drying of microparticles (0.75% low molecular weight chitosan dissolved in 0.4% of acetic acid) presented the best encapsulation efficiency (near 75%), with size ranges from 1.55 to 1.68 µm that allowed the encapsulation of 1.25-1.88 mg/mL of extract. Release studies of individual marjoram phenolic compounds at pH 2 and 7.4 showed that most of the compounds remained encapsulated in the microparticles. Only arbutin and vicenin II presented a high initial burst release. As the polarity of the compounds was reduced, their initial release decreased. In addition, after gastrointestinal digestion, most of marjoram phenolic compounds remained encapsulated. These results prove that chitosan microparticlescould protect the marjoram phenolic compounds during gastrointestinal digestion, specifically those related to anticancer activity, which enables their application as colon-specific delivery systems.

Probiotic-Assisted Colon-Specific Delivery of Anti-Inflammatory Drug – 5 ASA

Background: Mesalamine, one derivative of 5-aminosalicylic acid (5-ASA), has been recommended as the first-line medicine to induce and maintain remission in patients with mild-to-moderately active ulcerative colitis on account of its efficacy and safety. Objective: To evaluate the efficacy and safety of mesalamine in conjunction with probiotics for ulcerative colitis an ideal colon targeting system aims to deliver a therapeutic agent, selectively and effectively, to the colon. This system should ideally retain the drug release in the upper GI tract (stomach and small intestine); while trigger the drug release in the colon. Several approaches have been used to fabricate formulations to achieve a colon specific delivery of mesalamine such as; time dependent, enzymatic/microbial responsive approaches. This overview outlines the recent advances in mesalamine-colon delivery approaches for the potential treatment of ulcerative colitis and Crohn’ disease. Method: The matrix tablets of guar gum were prepared by wet granulation method Lactose, guar gum, talc and magnesium stearate were sifted separately through sieve number 60 to obtain particles of uniform size. Weighed quantity of Mesalamine was sifted through sieve number 100. Result: Matrix tablets containing Mesalamine were prepared by wet granulation method using guar gum as the colon targeting polymer and varying concentrations of probiotics Sporlac and Vivaflora to assist in colon targeting.

Formulation and Optimization of 5-Amino Salicylic acid Tablet for Colon Targeting

Objective: The objective of present work was to prepare colon-specific delivery systems for 5-aminosalicylic acid (5-ASA) using fenugreek gum and chitosan as a carrier target to the colon. Methods: Core tablets containing 5-ASA were prepared by wet granulation with using polyvinyl pyrolidone (PVP) as a binder and sodium starch glycolate as a super disintegrant. The prepared granules were evaluated for the angle of repose, compressibility index and Hausner’s ratio. The prepared tablets were evaluated the hardness, friability, weight variation and disintegration studies. The core tablets were coated with the concentration of 2%, 5%, and 7% in the ratio of 50:50, 40:60, 60:40, 70:30 and 30:70 of fenugreek gum and chitosan. The enteric coated tablets were characterized for the in vitro disintegration, and dissolution. The drug polymer compatibility studies were determined by using FT-IR study and found out no interaction between the drug and polymers. Results: The formation of complexes between fenugreek gum and chitosan prevents the drug release in the stomach. The tablets coated with 7% concentration solutions in the ratio 70:30 (Fenugreek gum: Chitosan) shows better swelling property and 89.99% drug releases in the colon. FT-IR, DSC studies showed the absence of interaction between 5-ASA and the excipients on storage accelerated condition at 40°C±2°C, 75%±5% RH for 12 weeks. Conclusion: Thus, it can be concluded that developed fenugreek gum and chitosan coated 5-ASA tablets can be considered as a promising system for targeted delivery to colon for local action.

Formulation development and Evaluation of Colon Specific Delivery System of Anti- amoebic Drug (Tinidazole) using different Polysaccharide carriers

Amoebiasis is an infection of the large intestine caused by Entamoeba histolytica. Tinidazole is the preferred drug used in the treatment of intestinal amoebiasis. The conventional tablet dosage form provides minimal amount of drug in the colon with undesirable adverse effect due to variation in the transit time. Hence, to target the drug directly to the site of action in the colon, there is need to develop colon targeted drug delivery systems that will enhance the therapeutic drug level, increases the bioavailability of active medicament and reduce the dose of drug. The fast disintegrating core tablet of Tinidazole was prepared by direct compression method. The core tablet was evaluated for hardness, thickness, Friability, weight variation, drug content, in vitro disintegration time and in vitro drug release studies. Using the optimized formulation (C3), different formulations (F1-F6) of coated tablet was prepared by using different polymers like chitosan and xanthan gum. The formulated coated tablet were evaluated for various parameters like for hardness, thickness, Friability, weight variation, drug content, swelling study and in vitro dissolution study. The optimized formulation F3 shows 6.24% drug release in Stomach and Small Intestine and maximum drug release up to 96.53% in the colon. The kinetic data analysis of formulations indicated that it fits to Korsmeyer -Peppas Model and follows zero order release kinetics. The mechanism of drug release from the tablet followed non-Fickian (super case-11) transport. The stability studies of the optimized formulation were investigated as per ICH guidelines. There were no significant changes in thickness, hardness, weight variation, friability, drug content and in vitro drug release. These findings suggest that compression coated tablet using polysaccharide carriers provide more site specific delivery, reduced degradation and release of drug in stomach and small intestine.

Preparation and in-vitro characterization of 5-aminosalicylic acid loaded hydrogels for colon specific delivery

The aim of the current investigation was to prepare and characterize the novel pH-sensitive hydrogels of pluronic F127 and sodium polystyrene sulfonate for the controlled delivery of 5-aminosalicylic acid to colon. Pluronic F127 and sodium polystyrene sulfonate were crosslinked with acrylic acid by N,N′-Methylene bisacrylamide. Various studies including porosity, drug loading, swelling, and drug release were performed for the fabricated hydrogels. Greater swelling and drug release were observed at high pH 7.4 as compared to pH 4.6 and 1.2, thus depicted pH-sensitive nature of developed hydrogel. Characterizations such as Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM), were performed in order to evaluate the crosslinking, thermal stability, crystallinity, and surface morphology of the fabricated hydrogel, respectively. The toxicity of the developed drug carrier system was investigated by the HET-CAM test and revealed no toxic effects on the chorioallantoic membrane of the chicken egg. Conclusively, the fabricated hydrogel could be applied as a potential alternate to conventional dosage forms for controlled release of 5-aminosalicylic acid for prolonged period of time.

Colon-specific delivery of isoliquiritigenin by oral edible zein/caseate nanocomplex for ulcerative colitis treatment.

Although a natural anti-inflammatory ingredient, isoliquiritigenin (ISL), plays an effective role in ulcerative colitis (UC) treatment, a series of drawbacks still limit its clinical application, including the poor solubility, instability in gastrointestinal tract, and rapid elimination rate of ISL. Zein-based NPs display the benefits on drug loading and delivery, whereas with the poor stability. In this study, an edible nano-system composed by zein/caseinate complex was fabricated for the colon-targeting delivery of ISL, to improve its colon retention and anti-UC effects. The optimized ISL loaded zein/caseinate NPs (ISL@NPs) were prepared by single-factor design by anti-solvent precipitation method, and then characterized. The improved cellular uptake of ISL@NPs on NCM460 and RAW 264.7 cells was evaluated in vitro. The colon tissue permeability and retention capacity in vivo, and the anti-UC efficacy of ISL@NPs in DSS-induce UC were implemented. As a result, ISL@NPs with the high drug loading efficiency of 9.39% ± 0.26%, the average particle diameter of 137.32 ± 2.54 nm, exhibited the pH-sensitive stability in the different simulated gastrointestinal buffer. Compared with free ISL, ISL@NPs showed significantly higher cellular uptake ability in NCM460 and RAW 264.7 cells. Based on in vivo imaging system, zein/caseinate NPs showed the prolonged colonic retention and the enhanced penetration into the colonic epithelium. Finally, the oral administration of ISL@NPs could effectively alleviate the UC-related symptoms, down-regulate the production of pro-inflammatory factors, and reduce the infiltration of macrophages and neutrophils in colon tissues. In this study, an oral colon-specific nano-system, composed with the natural compound and edible materials, was developed as the promising alternatives in the prevention and treatment of UC.

In-vitro evaluation of the 5-fluorouracil loaded GQDs@Bio-MOF capped with starch biopolymer for improved colon-specific delivery

Herein, for the first time, the photoluminescent graphene quantum dots@Bio-metal organic framework (GQDs@Bio-MOF) nanohybrid was prepared. BET analysis obtained the average pore diameter of GQDs@Bio-MOF about 11.97 nm. The existence of nanoscale porosity in GQDs@Bio-MOF displays its suitability for 5-Fu loading owing to the smaller size of 5-Fu. 5-Fu entrapment efficiency and loading capacity were found to be ~42.04 % and ~4.20 %, respectively (5-Fu@GQDs@Bio-MOF). The 5-Fu@GQDs@Bio-MOF was capped with starch biopolymer (St@5-Fu@GQDs@Bio-MOF), fabricated sample displayed 4.67 for pHPZC. SEM analysis displayed that the St@5-Fu@GQDs@Bio-MOF microspheres have a spherical shape with a diameter of ~2 μm. The in vitro drug release assay displayed better release behavior for St@5-Fu@GQDs@Bio-MOF than 5-Fu@GQDs@Bio-MOF, releasing about 62.3 % of the entrapped 5-Fu within 96 h of incubation. The 5-Fu release showed the best fitting with the Higuchi model with R2 0.9884. The in vitro cytotoxicity screening outcomes displayed that the St@GQDs@Bio-MOF is a promising biocompatible carrier, with cell viability of higher than 84 %. Accumulation of the results revealed that the St@5-Fu@GQDs@Bio-MOF is a new system with advantages of sustained drug release and biocompatibility that are the main criteria for each newly designed anticancer drug carrier.

Curcumin-Loaded Microspheres Are Effective in Preventing Oxidative Stress and Intestinal Inflammatory Abnormalities in Experimental Ulcerative Colitis in Rats.

Curcumin’s role in the treatment of ulcerative colitis (UC) has been proven by numerous studies, but its preventive administration, with the aim of reducing the remission episodes that are characteristic of this disease, must be further investigated. This study investigates the effects of a novel curcumin-loaded polymeric microparticulate oral-drug-delivery system for colon targeting (Col-CUR-MPs) in an experimental model of UC. Male Wistar rats (n = 40) were divided into five groups (n = 8), which were treated daily by oral gavage for seven days with a 2% aqueous solution of carboxymethylcellulose sodium salt (CMCNa) (healthy and disease control), free curcumin powder (reference), Col-CUR-MPs (test) and prednisolone (reference) prior to UC induction by the intrarectal administration of acetic acid (AA), followed by animal sacrification and blood and colonic samples’ collection on the eighth day. Col-CUR-MPs exhibited an important preventive effect in the severity degree of oxidative stress that resulted following AA intrarectal administration, which was proved by the highest catalase (CAT) and total antioxidant capacity (TAC) levels and the lowest nitrites/nitrates (NOx), total oxidative status (TOS) and oxidative stress index (OSI) levels. Biochemical parameter analysis was supported by histopathological assessment, confirming the significant anti-inflammatory and antioxidant effects of this novel colon-specific delivery system in AA-induced rat models of UC. Thus, this study offers encouraging perspectives regarding the preventive administration of curcumin in the form of a drug delivery system for colon targeting.

Characterization Formulation and in Vitro Assesment of Pulsatile Drug Delivery of Montelukast Sodium

The Montelukast pulsatile delivery system was created with the goal of delivering the drug to the colon for successful treatment of nocturnal asthma. The microspheres were sealed within the insoluble hard gelatin capsule body with an erodible hydrogel plug to create a time delayed capsule. Emulsion solvent evaporation was used to make the microspheres. Based on dissolving tests, optimised microsphere formulations were designed. The entire device was enteric coated in order to overcome the variability in gastric emptying time and achieve colon-specific delivery. The hydrogel plug (HPMC K100 and lactose in a 1:1 ratio) with a hardness of 4.5kg/cm2 and a weight of 100 mg was placed in the capsule opening and found to be effective in delaying release of the drug in small intestinal fluid, ejecting the plug into colonic fluid, and releasing the microspheres into colonic fluid after a 5-hour lag time. Three dissolving medium with pH 1.2, 7.4, and 6.8 were employed consecutively to imitate pH fluctuations along the GI tract. The medication and polymer had no interaction, according to the FTIR analysis. Montelukast microspheres 1:4 ratio had the longest release time of all the formulations, lasting 12 hours. The results showed that the device is capable of delaying drug release for a programmable period of time and treating asthma. Keywords: Montelukast, hydrogel plugs, pulsatile delivery, nocturnal asthma, microspheres.

Colon specific delivery of miR-155 inhibitor alleviates estrogen deficiency related phenotype via microbiota remodeling

Compelling data have indicated menopause-associated increase in cardiovascular disease in women, while the underlying mechanisms remain largely unknown. It is established that changes of intestinal microbiota affect cardiovascular function in the context of metabolic syndrome. We here aimed to explore the possible link between host intestinal function, microbiota, and cardiac function in the ovariectomy (OVX) mouse model. Mice were ovariectomized to induce estrogen-related metabolic syndrome and cardiovascular defect. Microbiota was analyzed by 16s rRNA sequencing. miRNA and mRNA candidates expression were tested by qPCR. Cardiac function was examined by echocardiography. Colon specific delivery of miRNA candidates was achieved by oral gavage of Eudragit S100 functionalized microspheres. In comparison with the sham-operated group, OVX mice showed compromised cardiac function, together with activated inflammation in the visceral adipose tissue and heart. Lactobacillus abundance was significantly decreased in the gut of OVX mice. Meanwhile, miR-155 was mostly upregulated in the intestinal epithelium and thus the feces over other candidates, which in turn decreased Lactobacillus abundance in the intestine when endocytosed. Oral delivery of miR-155 antagonist restored the protective microbiota and thus protected the cardiac function in the OVX mice. This study has established a possible regulatory axis of intestinal miRNAs-microbiota-estrogen deficiency related phenotype in the OVX model. Colon specific delivery of therapeutic miRNAs would possibly restore the microbiota toward protective phenotype in the context of metabolic syndrome.

Studies on Jackfruit-Okra Mucilage-Based Curcumin Mucoadhesive Tablet for Colon Targeted Delivery.

The present work investigates a blend of jack fruit mucilage (JFM) and okra mucilage (OKM) as promising mucoadhesive carriers for colon-specific delivery of a curcumin (CMN)-loaded mucoadhesive tablet (CMT) formulation. Formulation optimization was performed using central composite design (CCD) to further decipher the effect of varying proportions of the mucoadhesive carriers JFM and OKG on response factors such as drug release (% DR) and mucoadhesive strength (MA). The optimized formulation CMT (F14) demonstrated a favorable 54.35% in vitro release of CMN in 12 h with release kinetics resulting from a zero-order anomalous diffusion mechanism and MA of 34.1733 ± 1.26 g. Accelerated stability testing of CMT (F14) confirmed a shelf life of about 4.7 years. In vivo drug targeting studies performed using rabbit models in order to observe transit behavior (colon-specific delivery) of the dosage form were assessed by fluoroscopic images of the GI tract. Taking the results together, the results confirm that the combination of JFM and OKM could be exploited as an ideal mucoadhesive carrier for effective delivery of macromolecules to the colon.

Formulation and Evaluation of Hydroxypropylmethylcellulose-dicyclomine Microsponges for Colon Targeted Drug Delivery: In Vitro and In Vivo Evaluation.

The objective of the present study was to design novel colon targeted delivery of Dicyclomine Hydrochloride (DCH) microsponges. Microsponges (MS1-MS4) based on different ratios of Hydroxypropylmethylcellulose (HPMC) and DCH were prepared by quasi-emulsion solvent diffusion method. Micro-sponges were analyzed by determining percent yield, encapsulation efficiency, drug content, drug-polymer compatibility and thermal stability. Kinetic analysis of thermal stability data was done by Chang method, Friedman method and Broido method. In vitro dissolution study was carried out at pH 1.2, pH 6.8 and pH 7.4 at different time intervals. Results showed that there was no chemical interaction between DCH and HPMC in all microsponge formulations. Production yield, drug content and encapsulation efficiency were enhanced on increasing the drug-polymer ratio. Thermal stability of all the micro-sponges was greater than that of pure drug. In vitro drug release was decreased on increasing the polymer concentration at different pH levels. The newly prepared micro-sponges based on HPMC were confirmed as a promising means of colon-targeted delivery of DCH. An HPLC method was developed and validated for the bioequivalence study of newly designed microsponges. Pharmacokinetics parameters were calculated using the linear trapezoidal method after single oral administration of microsponges in white albino rabbits. Pharmacokinetics results indicate an enhancement in the value of t1/2, tmax, Cmax and AUC0-t of DCH in the microsponges as compared to standard DCH showing enhanced bioavailability of the drug after microsponges formation. The current study shows a new approach for colon-specific delivery of DCH based on microsponges.

Design and Development of Ornidazole Loaded Polymeric Nanoparticles

This research describes the preparation of ornidazole (ORZ) polymeric nanoparticles by using chitosan as polymer for colon-specific delivery. The polymeric nanoparticles were prepared by the ionic gelation method. The nanoparticles were evaluated for their in vitro drug release properties. Scanning electron microscopy was used for morphology observation. The nanoparticles exhibited mucoadhesive properties, which diminished with increasing drug content. The nanoparticles with a particle size range between 180 and 280 nm exhibited excellent mucoadhesive properties. The results shown that the formulated nanoparticles have succeeded in controlling the release of (ORZ) over a 14-hr period. In conclusion, the release of ORZ was found to be dependent upon the composition of the nanoparticles, the ratio of the components and possible particle size, as well as bioadhesive ability.

PH-sensitive liposomes for colonic co-delivery of mesalazine and curcumin for the treatment of ulcerative colitis

The ineffectiveness of the current management of ulcerative colitis (UC) demands novel pharmaceutical techniques and advance therapeutic strategies to facilitate safe and efficacious treatment of the disease. In this quest, mesalazine (MZ), a 5-aminosalicylate with anti-inflammatory and potent antioxidant activities, along with curcumin (CM), a natural anti-inflammatory and antioxidant polyphenol, were found to produce a synergistic efficacy to efficiently alleviate UC. In the present study, we have formulated pH-sensitive liposomes (LS) containing a low-dose combination of MZ and CM as a potential therapy for UC. It was hypothesized that the synergistic action of the two drugs, pH-dependent colon-specific delivery, and use of LS as a nano-technological drug carrier system could diminish drug-associated side effects, reduce the dose and provide effective treatment strategy for UC. The guinea pig model of UC was used to evaluate the in vivo efficacy of pH sensitive MZ-CM co-loaded LS and found to be more efficacious than single-drug LS or drug solution. Furthermore, both drugs exhibited high antioxidant activity and mitigated the oxidative stress present along UC; resulting in an effective treatment of UC. In conclusion, eudragit-S100 coated MZ-CM liposomes is a promising treatment strategy for the effective oral therapy of UC.

Discovery of a Colon-Targeted Azo Prodrug of Tofacitinib through the Establishment of Colon-Specific Delivery Systems Constructed by 5-ASA-PABA-MAC and 5-ASA-PABA-Diamine for the Treatment of Ulcerative Colitis.

To mitigate the systemic adverse effects of tofacitinib, 5-ASA-PABA-MAC and 5-ASA-PABA-diamine colon-specific delivery systems were constructed, and tofacitinib azo prodrugs 9 and 20a-20g were synthesized accordingly. The release studies suggested that these systems could effectively release tofacitinib in vitro, and the 5-ASA-PABA-diamine system could successfully realize the colon targeting of tofacitinib in vivo. Specifically, compound 20g displayed a 3.67-fold decrease of plasma AUC(tofacitinib,0-∞) and a 9.61-fold increase of colonic AUC(tofacitinib,0-12h), compared with tofacitinib at a molar equivalent oral dose. Moreover, mouse models suggested that compound 20g (1.5 mg/kg) could achieve roughly the same efficacy against ulcerative colitis compared with tofacitinib (10 mg/kg) and did not impair natural killer cells. These results demonstrated the feasibility of compound 20g as an effective alternative to mitigate the systemic adverse effects of tofacitinib, and 5-ASA-PABA-MAC and 5-ASA-PABA-diamine systems were proven to be effective for colon-specific drug delivery.

Hemoglobin bio-adhesive nanoparticles as a colon-specific delivery system for sustained release of 5-aminosalicylic acid in the effective treatment of inflammatory bowel disease

A colonic drug delivery system was developed to specifically deliver 5-aminosalicylic acid (5-ASA) to the inflamed site by conjugating with hemoglobin nanoparticles (HbNPs). The 5-ASA-HbNPs (eight 5-ASA molecules per Hb molecule) with the size of 220 nm and zeta potential of −14.6 mV is a tailored nanoparticle able to pass through the mucus layer. The 5-ASA-HbNPs do not undergo chemical and enzymatic hydrolysis in the simulated gastrointestinal fluids over 6 h. Significantly higher cellular uptakes and prolonged release was seen for the 5-ASA-HbNPs in Caco-2 cells, compared to free 5-ASA over 72 h. In addition, 5-ASA-HbNPs revealed similar therapeutic effectiveness with free 5-ASA against tumor necrosis factor and showed less inhibitory concentration (IC50) for myeloperoxidase enzyme activity. In vivo imaging of mouse demonstrated the localization of drug in the descending colon after oral administration and about 15% of the administered dose was recovered as 5-ASA from urine in 6 h. The use of these nanoparticles with the mucus adhesion properties and permeability to intestinal epithelial cells can be a good candidate with potential application in the colonic drug delivery field.