Oral Colon-specific Drug Delivery Research Articles

Development of Resistant Starch-Pectin Microsphere for Improving Oral Colon-specific Drug Delivery of 5-Fluorouracil

Conventional chemotherapy is ineffective for colorectal cancer as the drug moiety does not reach its intended site. 5-Fluorouracil (5-FU) microspheres aimed at colon-specific drug delivery have been developed by using the solvent evaporation technique in this study. The influence of utilizing different percentages of resistant starch-pectin polymer on the drug loading, encapsulation efficiency, and release behavior of the drug was investigated. The characterization of prepared microspheres was done by shape, surface morphology, drug loading, encapsulation efficiency and in vitro drug release studies. Drug-polymer interactions and drug stability were investigated by Differential Scanning Calorimetry (DSC) and FTIR spectroscopy. The 5-Fluorouracil polymeric microspheres that were formulated utilizing a resistant starch (RS) and pectin polymer displayed ideal physicochemical properties and spherical particles. The targeted microspheres demonstrated a high drug loading, encapsulation efficiency, and a satisfactory drug release pattern over the time period of 8 hours. Studies on drug release conducted under conditions that simulate stomach to colon transit have demonstrated that the drug was prevented from being released in the physiological conditions of the stomach and small intestine. Creating a new multiparticulate system using RS-pectin microspheres in order to forecast the protection that the combination might provide to the dosage form that will ensure localized drug release in the colon. Finally, it was found that the 5-Fluorouracil polymeric microsphere is a suitable microcarrier for effective colon-specific drug delivery tools with increased chemotherapeutic efficacy. Bangladesh Pharmaceutical Journal 26(1): 36-44, 2023 (January)

Development of Budesonide Oral Colon Specific Drug Delivery System using Interpolymer Complexation Method

Abstract: Background: Oral bioavailability of Budesonide is 10% due to its extensive first pass metabolism, its high volume of distribution and 85-90% of protein binding. Protection of drug release in stomach and targeting drug to colon which is an absorption site of drug is an attempt to improve therapeutic efficacy. The objective of this study was to develop interpolymer complex microspheres of Budesonide for oral colon specific drug delivery. Methods: Emulsion solvent evaporation method was used in the preparation of microspheres. Microspheres prepared at different polymer ratio and surfactant concentration were analysed for its mean particle size, surface morphology, flow property, drug release, % encapsulation efficiency. Results: Microspheres prepared with 3:5 polymer ratios F4 was optimized with respect to its % EE, in vitro drug release and percentage yield. Drug release from formulated tablets containing microspheres of 3:5 polymer ratios showed an extended release up to 12 h in pH buffer 7.4. Interpolymer complexation was confirmed by FT-IR studies, compatibility of drug with excipients by DSC indicated no significant changes with drug. SEM studies revealed formation of round microspheres with pervious and uneven surface. In vitro release data from microspheres was analysed by kinetic model fitting for mechanism of drug release. Microspheres showed 5-10% of drug release in pH 1.2 which was further prevented by formulating coated tablets of microspheres using cellulose acetate phthalate. Conclusion: Targeted colon specific drug delivery of Budenoside with extended release up to 12 h was successfully achieved by formulation of tablets containing microspheres prepared by interpolymer complexation technique. Key words: Budesonide, Colon Specific Delivery, Interpolymer Complexation, Microspheres, Cellulose Acetate phthalate.

A novel and simple oral colon-specific drug delivery system based on the pectin/modified nano-carbon sphere nanocomposite gel films

The 3-aminopropyltriethoxysilane modified nano-carbon sphere (MNCS) was added into pectin-Ca2+ film to improve the controlled release properties of the pectin-based oral colon-specific drug delivery system (OCDDS). The FT-IR measurements indicated the successful modification of nano-carbon sphere via silylation reaction and the electrostatic interaction between the pectin molecules and MNCS in the composite film. The FE-SEM showed the pore structure when the MNCS was mingled with the pectin. The 5-fluorouracil (5-FU) was employed as the drug model and the controlled release properties of the corresponding OCDDSs were determined. The values of the encapsulation efficiency ranged from 30.1% to 52.6%. All composite film based OCDDSs presented higher encapsulation efficiency than single pectin-Ca2+ based OCDDS. The drug release studies emerged that almost all the OCDDSs from composite films presented better release properties than single pectin-Ca2+ based OCDDS. The sample C revealed best release performance with the cumulative release rate of 32.17%, 22.77% and 63.89% in the simulated gastric fluid, small intestinal fluid and colon fluid, respectively. In addition, the kinetics studies were performed to analyze the release data. The cytotoxicity assay indicated good biocompatibility of the composite carriers.

Chemical cross-linking approach for prolonging diclofenac sodium release from pectin-based delivery system

To overcome the instability of pectin-Ca2+ gels based oral colon-specific drug delivery system (OCDDS) in the upper gastrointestinal tract, the chemical cross-linked pectin carriers were prepared by adding succinic anhydride and glutaric dialdehyde as the cross-linking reagents. The diclofenac sodium was employed as the water-soluble drug model to calculate the controlled release properties. The encapsulation efficiency and loading efficiency were measured and the sample PG1 shows the best efficiency of 78.81% and 7.78%, respectively. The simulative release rate was estimated and the cumulative release rate of sample PG1 reached to a maximum of 3.04, 3.66 and 79.43% in SGF, SSIF and SCF. The release data was employed to fit the First order, Higuchi, Bhaskar, and Ritger-peppas model and the goodness of the fit was calculated by the regression coefficient. The succinic anhydride and glutaric dialdehyde cross-linked pectin were characterized by FTIR to prove the cross-linking reaction. In addition, FE-SEM characterization of sample PG1 indicated the rally microsphere with smooth surface. The sample PG1 after the digestion was also characterized by the FE-SEM, and irregularly structure was obtained.

Enzyme-responsive mechanism based on multi-walled carbon nanotubes and pectin complex tablets for oral colon-specific drug delivery system

The purpose of this work was to explore the potential application of MCNT as a colon-specific delivery system based on the enzyme responsive mechanism. A novel type of enzyme-sensitive colon-specific tablet (PM-tablet) based on pectin and multi-walled carbon nanotube (MCNT) was prepared by wet granulation tabletting method. The PM-tablet in the presence of pectinase exhibited enzyme degradation release and achieve a precise release in the colon. Our study had proposed a novel idea for the application of MCNT on the oral colon-specific drug delivery system.

Design and evaluation of rhubarb total free anthraquinones oral colon-specific drug delivery granules to improve the purgative effect

Rhubarb is commonly used as a cathartic in Asian countries. However, researchers have devotedextensive concerns to the quality control and safety of rhubarb and traditional Chinese preparations composed of rhubarb due to the instable purgative effect and potential nephrotoxicity of anthraquinones. In this study, we aimed to prepare rhubarb total free anthraquinones (RTFA) oral colon-specific drug delivery granules (RTFA-OCDD-GN) to delivery anthraquinones to colon to produce purgative effect. RTFA-OCDD-GN were prepared using chitosan and Eudragit S100 through a double-layer coating process and the formulation was optimized. Continuous release studies were performed in a simulated gastric fluid (pH 1.2), followed by a small-intestinal fluid (pH 6.8) and a colonic fluid (pH 7.4, containing rat cecal contents). The purgative effect test was performed in rats. The dissolution profile of RTFA-OCDD-GN showed that the accumulative dissolution rate of RTFA was about 83.0% in the simulated colonic fluid containing rat cecal contents and only about 9.0% in the simulated gastrointestinal fluids. And the RTFA-OCDD-GN could produce the comparative purgative activity as rhubarb, suggesting it could deliver the free AQs to the colon. The RTFA-OCDD-GN was a useful media to enhance the purgative activity of free anthraquinones after administered orally.

In vitro drug release from acetylated high amylose starch-zein films for oral colon-specific drug delivery

This study describes the preparation of free films of zein with and without acetylated high amylose maize starch (HAS) and their corresponding coated tablets as a novel approach to colonic drug delivery. We hypothesise that the embedding of a digestible starch component within the inert zein would allow the film to remain intact until the large intestine is reached. Free films of zein alone and starch/zein were prepared and characterized. SEM and AFM images of film surface showed that films were morphologically inhomogeneous, particularly at lower HAS/Zein ratios; however, nanothermal analysis data suggested that these differences in appearance within the same film are not compositional differences. Moreover, FT-IR could detect no molecular interaction between the two polymers. Paracetamol tablets were coated with HAS/Zein aqueous based coatings of different compositions to a TWG of 20%. Drug release from zein alone and 1:5 HAS/Zein coated tablets under upper gastrointestinal conditions (pH 1.2, pH 6.8 with pepsin and pancreatin included) was very similar (for example approximately 12% and 14% of the drug was released, respectively, after 6 h in a sequential in vitro test), suggesting that release in this region is limited and is not influenced by the presence of HAS in the ratio to zein under study. Studies using an in vitro colon model showed that under simulated colonic conditions, the drug release was significantly (p < 0.05) more rapid from 1:5 HAS/Zein, compared to the zein alone coating formulation. These data therefore support the potential use of zein-starch mixed films for colonic targeting purposes.

Starch film-coated microparticles for oral colon-specific drug delivery

The aim of this study was to prepare and characterize a novel type of starch-coated microparticles (MPs) allowing site-specific delivery of bioactives to the colon. An oral colon-specific controlled-release system was developed in the form of MPs coated with a resistant starch (RS2/RS3) film (RS@MPs) through an aqueous suspension coating process. The RS2 was chosen from a high-amylose cornstarch with 88.5% digestion resistibility. The RS3 was prepared by a high-temperature/pressure (HTP) treatment, with the following of enzymatic debranching, and retrogradation, resulting in a dramatic increase in enzymatic resistance (RS3 content: 76.6%). RS@MPs showed 40.7% of 5-aminosalicylic acid release within 8 h. The in vivo study of fluorescein-loaded RS@MPs indicated the high acidic and enzymatic resistibility of RS@MPs and a restrained release in the upper GIT. Therefore, RS@MPs has revealed to be a high potential system for accurately targeting bioactive compound delivery to the colon.

The rhubarb total free anthraquinone oral colon-specific drug delivery granules: Comparative pharmacokinetics study with rhubarb by UPLC-MS/MS after oral administration

ObjectiveThis study aimed to compare pharmacokinetics of rhubarb total free anthraquinones (AQs) oral colon-specific delivery granules (RTFA-OCDD-GN) and rhubarb after oral administration to evaluate the colonic-target releasing characteristic of RTFA-OCDD-GN and the impact of five AQs components on the contribution of the attenuation of nephrotoxicity. MethodsThe compare pharmacokinetics of RTFA-OCDD-GN and rhubarb was performed in rats. The plasma concentrations of aloe-emodin, rhein, emodin, chrysophanol and physcion were assayed by a validated UPLC-MS/MS method. ResultsThe pharmacokinetics results showed that the AUC0-72h of aloe-emodin, emodin, chrysophanol and physcion was decreased by 3.09-fold (p < 0.05), 2.68-fold (p < 0.05), 2.97-fold (p < 0.01) and 2.84-fold (p < 0.05) respectively in group RTFA-OCDD-GN; whereas the AUC0-72h of rhein was increased slightly by 1.05-fold (p > 0.05) compared with group rhubarb samples. However the dose-normalized AUC0-72h of aloe-emodin, rhein, emodin and chrysophanol was decreased by 1.90-fold (p < 0.05), 1.82-fold, 1.33-fold and 2.27-fold (p < 0.01) respectively in RTFA-OCDD-GN group; whereas the dose-normalized AUC0-72h of physcion was increased by 2.33-fold (p < 0.01) compared with group rhubarb samples. ConclusionThese differences on pharmacokinetic parameters indicated that RTFA-OCDD-GN delivered AQs to colon. The systemic exposure reduction of aloe-emodin, emodin and physcion in group RTFA-OCDD-GN could contribute to the attenuation of nephyrotoxicity caused by rhubarb.

Oral colon-specific drug delivery system reduces the nephrotoxicity of rhubarb anthraquinones when they produce purgative efficacy.

Rhubarb is commonly used to treat constipation in China and anthraquinones (AQs) are the active components present in rhubarb. However, an increasing number of studies have reported that AQs induce nephrotoxicity. In the present study, rhubarb total free anthraquinones (RTFA) oral colon-specific drug delivery granules (RTFA-OCDD-GN) were prepared to determine whether RTFA-OCDD-GN could reduce the nephrotoxicity that occurs when AQs produce purgative efficacy. RTFA-OCDD-GN were prepared using pH-enzyme double-layer coating technology and the cumulative release rate of RTFA in RTFA-OCDD-GN was assessed. The first black stool time, the number and state of feces over 8 h were observed to measure the purgative efficacy. In the nephrotoxicity test, biochemical and histopathological examinations were performed following 20 and 40 days administration, and 20 days convalescence. The cumulative release rate of RTFA in RTFA-OCDD-GN was >80% in simulated colonic fluid. RTFA-OCDD-GN produced considerable purgative efficacy compared with rhubarb medical material samples (RMMS). Following 40 days RMMS administration, blood urea nitrogen, creatinine and urine β2-microglobulin levels in the high-dosage group were significantly increased compared with the control and RTFA-OCDD-GN groups (P<0.05). All specimens from the high-dosage RMMS group exhibited swelling/degeneration of renal proximal convoluted tubule epithelial cells. No difference in pathological conditions and biochemical indicators was detected between the RTFA-OCDD-GN groups and the control group. The nephrotoxicity of AQs was significantly reduced following RTFA-OCDD-GN administration, which produced considerable purgative efficacy compared with RMMS.

Colon targeted oral drug delivery system based on alginate-chitosan microspheres loaded with icariin in the treatment of ulcerative colitis

In recent years, oral colon specific drug delivery system has been paid more attention in the treatment of inflammatory bowel disease (IBD). As the special pH condition in gastrointestinal tract, the challenge for treatment of IBD was that the colon drug delivery system should endure the low pH in stomach and release drugs quickly in high pH in colon. Icariin with the poor solubility and low bioavailability limited the treatment of many diseases in clinic. In this study, the protective mechanism of alginate-chitosan microspheres loaded with icariin were investigated with trinitrobenzene sulfonic acid (TNBS)/ethanol induced colonic mucosal injury in rats. The results of drug release showed that the icariin loaded into microspheres released only 10% in simulated gastric fluid and a high amount of 65.6% released in simulated colonic fluid. The fluorescence tracer indicated high retention of targeted microspheres more than 12h in colon. The microspheres loaded with icariin could not only reduce the colonic injury by decreasing the colon mucosa damage index in rats, but also reduce the inflammatory response by reducing the production and gene expression of inflammatory mediators and cytokines in colonic mucosa. All the results indicate that targeted microspheres loaded with icariin could exert the colon-protective effects through reducing the inflammatory response, which would be developed as a potential drug controlled release system for treatment of ulcerative colitis.

Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery

A safe and efficient nanocomposite hydrogel for colon cancer drug delivery was synthesized using pH-sensitive and biocompatible graphene oxide (GO) containing azoaromatic crosslinks as well as poly (vinyl alcohol) (PVA) (GO–N=N–GO/PVA composite hydrogels). Curcumin (CUR), an anti-cancer drug, was encapsulated successfully into the hydrogel through a freezing and thawing process. Fourier transform infrared spectroscopy, scanning electron microscopy and Raman spectroscopy were performed to confirm the formation and morphological properties of the nanocomposite hydrogel. The hydrogels exhibited good swelling properties in a pH-sensitive manner. Drug release studies under conditions mimicking stomach to colon transit have shown that the drug was protected from being released completely into the physiological environment of the stomach and small intestine. In vivo imaging analysis, pharmacokinetics and a distribution of the gastrointestinal tract experiment were systematically studied and evaluated as colon-specific drug delivery systems. All the results demonstrated that GO–N=N–GO/PVA composite hydrogels could protect CUR well while passing through the stomach and small intestine to the proximal colon, and enhance the colon-targeting ability and residence time in the colon site. Therefore, CUR loaded GO–N=N–GO/PVA composite hydrogels might potentially provide a theoretical basis for the treatment of colon cancer with high efficiency and low toxicity.

Role of Polysaccharides in Colon-Specific Drug Delivery

Copyright © 2015, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited. Oral colon delivery has gained wide interest not just for the treatment of local diseases of the colon, such as inflammatory bowel disease (IBD) or Crohn’s disease, but also as a reliable approach for peptide and protein drug delivery (1). Owing to the distal location of the colon in the gastrointestinal (GI) tract, an oral colon-specific drug delivery system must withstand the conditions in the upper GI tract and should rapidly release the drug upon entry into the colon. The slow movement of material through the colon allows the presence of a large microbial population, much greater than that in the stomach or small intestine. These bacteria produce a wide range of reductive and hydrolytic enzymes, many of which are not present in the upper GI tract (2). Therefore, taking susceptibility to degradation by colonic enzymes into consideration, different natural or synthetic polymers have been employed in approaches such as prodrugs, hydrogels, matrices, and biodegradable coating materials. These polymers protect the drug from the conditions in the upper GI tract and undergo degradation via cleavage by colonic microbial enzymes, thus enabling drug release in the colon environment. A large number of polysaccharides are resistant to degradation by gastric and intestinal bacteria and are specifically hydrolyzed by colonic microbial flora; thus, they show potential for use as colon-specific drug delivery systems (3). Naturally occurring polysaccharides originate from plants (pectin, inulin and guar gum), animals (chitosan and chondroitin sulfate), algae (alginates), or bacteria (dextran). They are inexpensive, non-toxic, and have varied structures and properties. Furthermore, because of their safety and biocompatibility characteristics, these polysaccharides have also been widely used as excipients in the pharmaceutical industry. The problems typically encountered with polysaccharides are their high water solubility and poor filmforming property, which can lead to premature drug release from polysaccharide-based systems at off-target sites. Several methods have been used to overcome these obstacles. One way of decreasing the solubility of polysaccharides is to make them more water-resistant and yet enzymatically degradable by using derivatives such as calcium-bound pectin (4). The other approaches are based on combining polysaccharides with other insoluble film-forming polymers that limit the hydration of polysaccharides and thus inhibit premature drug release. In this respect, various polymers such as ethyl cellulose and polymethacrylates (5) have been used. The formation of polyelectrolyte complexes with an anionic (pectin) and a cationic polysaccharide (chitosan) was successfully assessed (6). Most recently, a combination of a polysaccharide-based system and the other colonic delivery systems such as pHand time-dependent polymers have been the broad direction of interest because of the significant advantages of site-specificity of drug release in the colon. and owing to the various benefits of naturally occurring polysaccharides.

Oral administration of pH-sensitive curcumin-loaded microparticles for ulcerative colitis therapy

Oral colon-specific drug delivery is of great interest for ulcerative colitis (UC) therapy. Here, an emulsion-solvent evaporation method was used to fabricate microparticles (MPs) with pH-sensitive Eudragit S100 (ERS100) and poly(lactide-co-glycolide) (PLGA), and the MPs were loaded with curcumin (an efficient anti-inflammatory agent). The resultant spherical MPs had a desirable particle size ranging from 1.52 to 1.91μm. Their loading efficiency could be regulated by changing the weight ratios of ERS100 and PLGA, with some MPs exhibiting loading efficiencies over 80%. It was observed that the fast release of curcumin from MPs in buffers (pH 1.2 and 6.8) could be significantly decreased by increasing the PLGA content. ERS100/PLGA MPs with a weight ratio of 1:2 (MPs-4) were able to maintain sustained release of curcumin, releasing ∼48% of the initial drug load at pH 7.2–7.4 during a 20h-incubation. Most importantly, in vivo experiments revealed that orally administered MPs-4 had a superior therapeutic efficiency in alleviating colitis in a UC mouse model, compared to curcumin. Collectively, our one-step-fabricated curcumin-loaded MPs have the properties of pH-sensitivity, controlled drug release and colon targeting, and thus, may hold promise as a readily scalable drug carrier for the efficient clinical treatment of UC.

The pharmacokinetic study on the mechanism of toxicity attenuation of rhubarb total free anthraquinone oral colon-specific drug delivery system

Rhubarb is commonly used as laxatives in Asian countries, of which anthraquinones are the major active ingredients, but there are an increased number of concerns regarding the nephrotoxicity of anthraquinones. In this study, we compared the pharmacokinetic characteristics of rhubarb anthraquinones in rats after orally administered with rhubarb and rhubarb total free anthraquinone oral colon-specific drug delivery granules (RTFA-OCDD-GN), and then explained why these granules could reduce the nephrotoxicity of anthraquinones when they produced purgative efficacy. A sensitive and reliable high performance liquid chromatography (HPLC) method has been fully validated for simultaneous determination of the five active components of rhubarb, and successfully applied to investigate and compare the remarkable differences in pharmacokinetic study of rhubarb anthraquinones after orally administered with rhubarb and RTFA-OCDD-GN. The results showed that, compared with rhubarb group, the AUC, Cmax, t1/2z and Vz/F of aloe-emodin, rhein, emodin and chrysophanol in rats receiving the RTFA-OCDD-GN were significantly decreased, and the Tmax of the four analytes was prolonged. Moreover, the Tmax of rhein, the Cmax of chrysophanol and emodin all have significant differences (P<0.05). Simultaneously, anthraquinone prototype excretion rates in urine and feces of aloe-emodin, rhein, emodin, chrysophanol and physcion were all increased. These findings suggested that oral colon-specific drug delivery technology made anthraquinone aglycone to colon-specific release after oral administration. This allowed anthraquinones to not only play the corresponding purgative effect but also avoid intestinal absorption and promote excretion. And thereby greatly reduced the nephrotoxicity of rhubarb. The result is a new breakthrough in rhubarb toxicity attenuated research.

The New Progress and Outlook of Oral Colon-specific Drug Delivery System for Treating Cancer

The morbidity of colon cancer is increasingly frequent in past years. Although quite a few researches about colon targeted drugs have achieved certain results and there are quite a few drugs for treatment at present, insufficient of dosage form and function still exists. The paper will give an outlook about a kind of multi-functional colon targeted delivery system.

Modified Approaches for Colon Specific Drug Delivery System: A Review

The colon is a site where both local and systemic delivery of drugs can take place. Local delivery allows topical treatment of inflammatory bowel disease. However, treatment can be made effective if the drugs can be targeted directly into the colon, thereby reducing the systemic side effects. This review mainly describes 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. Oral administration of different dosage forms is the most commonly used method due to flexibility in design of dosage form and high patient acceptance, but the gastrointestinal tract presents several formidable barriers to drug delivery. In oral colon-specific drug delivery system, colon has a large amount of lymphoma tissue (facilitates direct absorption in to the blood), negligible brush boarder membrane activity, and much less pancreatic enzymatic activity as compared with the small intestine. Colon-specific drug delivery has gained increased importance not just for the delivery of the drugs for treatment of local diseases associated with the colon but also for its potential for the delivery of proteins and therapeutic peptides. Different approaches are designed based on prodrug formulation, pH-sensitivity, time-dependency (lag time), microbial degradation and osmotic pressure etc to formulate the different dosage forms like tablets, capsules, multiparticulates, microspheres, liposomes for colon targeting. The delivery of drugs to the colon has a number of therapeutic implications in the field of drug delivery. In the recent times, the colon specific delivery systems are also gaining importance not only for local drug delivery of drugs but also for the systemic delivery of protein and peptide drugs. This review updated the research on different approaches formulation and evaluation of colon-specific drug delivery.

Preparation, &lt;I&gt;In Vitro&lt;/I&gt; and &lt;I&gt;In Vivo&lt;/I&gt; Evaluation of Budesonide Loaded Core/Shell Nanofibers as Oral Colonic Drug Delivery System

Budesonide (BUD) loaded ethylcellulose (EC)-core/Eudragit S100-shell nanofibers (BUD-core/shell-NFs) have been successfully prepared using a coaxial electrospinning technique. The drug encapsulation efficiency was 90.48%. SEM and TEM analysis showed that fine core-shell structured nanofibers with an average diameter 190 nm and uniform core diameters 74 nm were prepared. The BUD-loaded Eudragit S100/EC composite nanofibers (BUD-NFs) were prepared using a blend electrospinning method and used as a control. In vitro release tests in HCl 0.1 N, phosphate buffer solutions pH 6.8 and 7.4 were studied. Moreover, the colon-specific characteristics were directly proven in vivo by the content of BUD in different segments of the gastrointestinal (GI) tract in rats after oral administration. Taken together, the results confirmed that BUD-core/shell-NFs had desired pH-dependent drug release profile, displayed a sustained and complete drug release in the colon, as well as protected BUD from being released completely in the upper portion of the GI tract. Compared with BUD-NFs, the BUD-core/shell-NFs have much better potential to be developed as oral colon-specific drug delivery system (OCDDS) to overcome the disadvantages of current oral formulations of BUD.

A novel hydrogel plug of Sterculia urens for pulsatile delivery: in vitro and in vivo evaluation

The objective of this study was to investigate a novel hydrogel plug using isolated root mucilage of Sterculia urens to obtain a desired lag time for an oral chronotherapeutic colon-specific pulsatile drug delivery of indomethacin. Pulsatile drug delivery was developed using chemically treated hard gelatin capsule bodies filled with eudragit multiparticulates of indomethacin, and sealed with different hydrogel plugs (root mucilage of S. urens, xanthan gum, guar gum, HPMC K4M and combination of maltodextrin with guar gum). Indomethacin multiparticulates were prepared using extrusion spheronization, spray drying and solvent evaporation techniques with Eudragit® L-100 and S-100 (1:2) by varying drug-to-polymer ratio. After oral administration, the water-soluble cap of capsule dissolved in the intestinal fluid and the hydrogel plug swells. After a controlled time, the swollen plug subsequently ejected from the dosage form, releases the contents of the capsule. The formulation factors affecting the drug release were concentration and types of hydrogel plug used. In vivo gamma scintigraphy study in healthy rabbits proved the capability of the system to release drug in lower parts of the gastrointestinal tract after a programmed lag time. This study demonstrates that the indomethacin multiparticulates could be successfully colon-targeted by the design of time and pH-dependent modified chronopharmaceutical formulation. In conclusion, the investigated novel hydrogel plug could be a valuable tool for achieving desired lag time.

PH-controllable release using functionalized mesoporous silica nanoparticles as an oral drug delivery system

We designed a novel oral colon-specific drug delivery system (OCDDS) using a modification of mesoporous silica nanoparticle (MSN) surfaces with pH-sensitive trimethylammonium (TA) groups through a pH-sensitive hydrazone bond. The pH-sensitive TA groups can efficiently increase the loading amounts of anionic drugs by a strong electrostatic attraction. After oral administration, the acidic pH of gastric juice can fully hydrolyze the TA–hydrazone bonds and further eliminate the positive charges of TA groups from MSN surfaces. When the hydrolyzed complexes were further delivered to the colon's pH of 7–8, a rapid and complete release of adsorbed drugs was observed. From the studies of spectroscopic characterizations, we demonstrated that the combination of pH-sensitive hydrazone–TA groups and nano-sized particles of the MSN carriers took the advantages of increasing the accessible surface areas of drug molecules and varying the charges of MSN surfaces, which can increase dissolution and release rate of hydrophobic drug molecules. In addition, a cell viability assay also indicated that no cytotoxicity of MSN–hydrazone–TA complexes was observed even with treatment in an extremely high nanoparticle concentration. Consequently, our new formulation is highly biocompatible for the OCDDS, and we can completely solve the low stability, low solubility, and low drug bioavailability in the free form of drug molecules for the design of OCDDS.