Carrier For Colon-specific Drug Delivery Research Articles

Characteristics of Interpolyelectrolyte Complexes Based on Different Types of Pectin with Eudragit® EPO as Novel Carriers for Colon-Specific Drug Delivery.

Given that pectin is a well-known substance used for drug delivery, we aimed to obtain and further examine the efficacy of interpolyelectrolyte complexes based on citrus or apple pectin and the Eudragit® EPO for using these carriers in oral drug delivery. To characterize the physicochemical properties of these compounds, turbidity, gravimetry, viscosity, elementary analysis, FTIR spectroscopy, and DSC analysis were utilized. Diffusion transport characteristics were evaluated to assess the swelling ability of the matrices and the release of diclofenac sodium. To examine the release parameters, mathematical modeling was performed by using the Korsmayer-Peppas and Logistic equations as well. During the turbidity study, stoichiometry compositions were selected for the developed IPECs EPO/PecA and EPO/PecC at pH values = 4.0, 5.0, 6.0, and 7.0. The FTIR spectra of the complexes were characterized by an increase in the intensity of the bands at 1610 cm-1 and 1400 cm-1. According to the DSC analysis, IPEC has a certain Tg = 57.3 °C. The highest release rates were obtained for IPEC EPO/PecC_1 and EPO/PecC_4. The mechanism of drug transport from the matrices IPEC EPO/PecC, IPEC EPO/PecA_3, and EPO/PecA_4 can be characterized as Super Case II. Anomalous release (non-Fickian release) is typical for IPEC EPO/PecA_1 and EPO/PecA_2. Thus, the resulting systems can be further used for the effective delivery of the drugs to the colon.

Highly cross-linked arabinoxylans microspheres as a microbiota-activated carrier for colon-specific insulin delivery

In vivo evaluation of arabinoxylans (AX) microspheres showed to protect insulin from degradation in the upper gastrointestinal tract and carrier insulin to colon. Insulin-loaded AX microspheres (50 UI/kg) decreased blood glucose level by 39% in diabetic rats with a maximum effect at 18 h post-administration, indicating that insulin remains bioactive. The continuous administration (4 days) of insulin-loaded AX microspheres improved the polyuria and increased the production of short-chain fatty acids, as well as Bifidobacterium and Bacteroides in diabetic rats compared to untreated diabetic rats. AX microspheres are a potential microbiota-activated carrier for colon-specific drug delivery and could be useful as a complementary treatment for diabetes.

Interpolymer Complexes of Eudragit® Copolymers as Novel Carriers for Colon-Specific Drug Delivery.

Interpolymer complexes (IPC) based on Eudragit® EPO and Eudragit® S100 were investigated as potential carriers for oral controlled drug delivery to the colon. IPC samples were prepared by mixing copolymer solutions in organic solvents (ethanol, isopropanol:acetone mixture (60:40, % v/v) and tetrahydrofuran). According to the data of elemental analysis, FTIR-spectroscopy, X-ray photoelectron spectroscopy and thermal analysis these IPCs have excess of anionic copolymer (Eudragit® S100) in their structure; they are stabilized by hydrogen and ionic intermacromolecular bonds and do not include free copolymer domains. IPC have pH-independent swelling properties in the media mimicking gastrointestinal tract (GIT) conditions and provide colon-specific delivery of indomethacin in buffer solutions (pH 1.2; 5.8; 6.8; 7.4) and in biorelevant media (fasted state simulated gastric fluid, fasted state simulated intestinal fluid—version 2 and fasted stated simulated colonic fluid).

Enzyme and PH responsive 5-flurouracil (5-FU) loaded hydrogels based on olsalazine derivatives for colon-specific drug delivery

Colon-specific drug delivery systems are efficient for increasing the availability of drugs at colon region and are desirable for the treatment of local diseases such as ulcerative colitis and colonic cancer. We synthesized an acryloyl chloride modified olsalazine (olsalazine-AC) as an azo crosslinker which was copolymerized with hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA), and developed two types of azo hydrogels which contained single network hydrogel and interpenetrating network hydrogel as an enzyme responsive and pH responsive controlled release carrier for colon-specific drug delivery. The structure of the azo crosslinker was characterized by FT-IR and 1H NMR spectra and the azo hydrogels were analyzed by using ultraviolet spectrophotometer and scanning electron microscopy. The in vitro release of the 5-flurouracil (5-FU) loaded azo hydrogels was carried out in PBS (pH 7.4), PBS (pH 2.0) and rat colonic fluid (RCF). The drug release profile revealed that 5-FU loaded in azo hydrogels released faster in rat colonic fluid. The results showed that these azo hydrogels could be potential drug carrier for colon-targeted delivery.

Inulin: A promising carrier for controlled and targeted drug delivery system

The delivery of a drug to the preferred site of action is referred to as drug targeting. The benefits of drug targeting are a reproducible and controlled release rate of the therapeutic compound, which forestalls overdose. Due to the potential to treat colonic diseases with minimum side effects, colon targeting has become of high interest over the last decades. Inulin was investigated for its potential as encapsulation material regarding its enzymatic degradability and its drug release behaviour. Inulin is a polysaccharide with a widespread range of therapeutic uses such as a carrier in a drug delivery vehicle, as a diagnostic/analytical tool or as a dietary fibre with additional health benefits. In the main, much research has focused on inulin as a drug delivery carrier for colon-specific drug delivery. The justification for this is its potential to survive in the stomach’s acidic environment. This unique stability and strength are utilized in many ways to deliver drugs safely to the colon, where they can be easily absorbed through the gut epithelium into the blood. There are also some proofs that inulin’s prebiotic features also lead to health benefits, mainly for patients with inflammatory bowel disease or in the prevention of colonic cancer. Inulin based hydrodynamic research will be useful to discover the potential of inulin.

Synthesis of Multiwalled Carbon Nanotubes–Poly(Methacrylic Acid) Nanohybrid Systems: Characterization, Thermal Properties, and In Vitro Release Studies of Naproxen as a Model Drug

ABSTRACTNanohybrid systems based on carbon nanotubes and pH-sensitive poly(methacrylic acid) were prepared through attaching polymer chains onto carbon nanotubes. First, polymerizable groups were attached onto carbon nanotube walls, then the polymerizable groups were copolymerized with different ratios of methacrylic acid. Obtained systems were studied and characterized through Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and transmission electron microscopy. A model drug (naproxen) was entrapped into the prepared materials and in vitro release studies were performed in pH 1 (simulated gastric fluids) and pH 7.4 (simulated intestinal fluids). It was noticed that release in simulated intestinal fluids was faster than simulated gastric fluids, therefore the prepared nanohybrid systems can be considered as appropriate carriers for colon-specific drug delivery.

Guar gum oleate-graft-poly(methacrylic acid) hydrogel as a colon-specific controlled drug delivery carrier

A novel type of ethylene glycol dimethacrylate (EGDMA) cross-linked guar gum oleate-graft-poly(methacrylic acid) (GGO-g-PMAc) hydrogel was prepared as a pH-responsive controlled release carrier for colon-specific drug delivery. The structure of GGO-g-PMAc hydrogel was characterized by FT-IR, 1H NMR and X-ray diffraction (XRD) analysis. The swelling degree of the GGO-g-PMAc hydrogel at pH 7.4 was found to be higher than that at pH 1.2. The drug release studies performed in pH 7.4 and 1.2 buffer solutions at 37°C revealed that the rate and amount of drug released from the GGO-g-PMAc hydrogel at pH 7.4 were higher than that at pH 1.2. The MTT assay revealed that there is no noticeable cytotoxicity of GGO-g-PMAc hydrogel at the concentration range of 0–100μg/ml against the mouse mesenchymal stem cell line (C3H10T1/2). These results suggested that GGO-g-PMAc hydrogel can be a prospective pH-sensitive carrier for colon-targeted drug delivery.

Guar gum succinate-sodium alginate beads as a pH-sensitive carrier for colon-specific drug delivery

Guar gum succinate − sodium alginate (GGS-SA) beads cross-linked with barium ions were prepared and characterized as a pH sensitive carrier for colon-specific drug delivery. The structure of GGS-SA beads was confirmed by FT-IR spectroscopy. Scanning Electron Microscope (SEM) studies revealed that the drug loaded GGS-SA beads prepared using 2:2 (w/v) weight percent of GGS and SA had a diameter about 1.4mm and roughly spherical in shape. X-ray diffraction (XRD) studies showed that the peaks corresponding to GGS and SA at 13.5°, 17.5°, 20.2° and 13.5°, 22°, 24.1°, respectively were destroyed in GGS-SA beads which show that these beads are more amorphous in nature. Swelling studies demonstrated the pH-dependent swelling behavior of GGS-SA beads. The beads showed higher swelling degrees in pH 7.4 than that in pH 1.2 due to the existence of anionic groups in the polymer chains. The drug release study showed that the amount of model drug, ibuprofen, released from the GGS-SA beads was higher in pH 7.4 than that in pH 1.2 due to the pH-dependent swelling behavior of the beads. MTT assay revealed that GGS-SA beads at a concentration range of 0–30μg/ml had no cytotoxic effect on the cultured mouse mesenchymal stem cells (C3H10T1/2). These results suggest that GGS-SA beads can be used as effective colon-specific drug delivery system with pH-dependent drug release ability.

Guar gum succinate as a carrier for colon-specific drug delivery

A novel type of pH-sensitive colon-specific controlled drug delivery carrier based on guar gum succinate (GGS) was prepared by reacting guar gum (GG) with succinic anhydride (SA) in the presence of 4-dimethylaminopyridine (DMAP). The formation of GGS was confirmed by FT-IR and 1H NMR and characterized using XRD techniques. GGS microparticles with 460–740μm in size were prepared using sodium trimetaphosphate (STMP) as a cross-linking agent. The size and morphologies of GGS microparticles were assessed by scanning electron microscopy (SEM). The swelling degree of the GGS microparticles was found to be higher in pH 7.4 than in pH 1.2. In addition, GGS microparticles showed a pH dependent drug release profile when compared to the GG microparticles. The MTT assay revealed that there is no apparent cytotoxicity of GGS against a mouse mesenchymal stem cell line at a concentration range of 0–200μg/ml. These results confirm that GGS could be used as a carrier for colon-specific drug delivery.

Gum ghatti-based biodegradable and conductive carriers for colon-specific drug delivery

Conductive superabsorbent hydrogels based on gum ghatti (Gg)/methacrylic acid (MAA)/aniline (ANI) were synthesized by gamma radiations initiated by two-step aqueous polymerization. A cross-linking agent N,N′-methylene-bis-acrylamide was used in the polymerization process, and MAA was graft-copolymerized onto Gg by γ-rays. Influence of preparative conditions (absorbed dose, monomers, solvent, and cross-linker concentrations) on the swelling behavior of cross-linked polymer systems has been investigated. Synthesized superabsorbent hydrogels were characterized using thermogravimetric analysis and swelling studies. In biodegradation study of synthesized hydrogels by composting soil method, Gg-cl-poly(MAA-ipn-ANI) showed better degradation efficiency in comparison to Gg-cl-poly(MAA). Synthesized hydrogels were loaded with amoxicillin trihydrate as a model drug to investigate the release behavior of hydrogels at different pH media. Kinetics studies revealed that synthesized hydrogels exhibit a Fickian diffusion behavior at pH 2.4 and 7.2. However, at pH 9.2, a non-Fickian diffusion behavior was observed which make them very suitable for colon-specific drug delivery applications.

The effect of polymer and CaCl2 concentrations on the sulfasalazine release from alginate-N,O-carboxymethyl chitosan beads.

In this study, pH-sensitive blended polymeric beads were prepared by ionic gelation of mixed alginate and N,O-carboxymethyl chitosan (NOCC) solutions in aqueous media containing calcium chloride. To prepare drug-loaded beads, sulfasalazine (SA) as a model drug was added to the initial aqueous polymer solution. These beads were characterized and evaluated in vitro as potential carriers for colon-specific drug delivery. A 32 full factorial experimental design was employed to evaluate the effect of polymer and CaCl2 concentrations on swelling and drug release behavior of the beads in simulated gastrointestinal tract fluid. It was found that the rate of swelling and drug release decreased significantly with increasing polymer and CaCl2 concentrations, but polymer concentration was more effective than CaCl2 concentration. The beads prepared using 4.5% polymer concentration and 4% CaCl2 concentration retained approximately 60% of the loaded drug before approaching the simulated colonic fluid. Based on the results, the alginate-NOCC beads prepared with high polymer concentration could be potentially suitable polymeric carriers for colon-specific delivery of SA.Electronic supplementary materialThe online version of this article (doi:10.1186/2194-0517-2-10) contains supplementary material, which is available to authorized users.

Hyaluronan–cisplatin conjugate nanoparticles embedded in Eudragit S100-coated pectin/alginate microbeads for colon drug delivery

Hyaluronan–cisplatin conjugate nanoparticles (HCNPs) were chosen as colon-targeting drug-delivery carriers due to the observation that a variety of malignant tumors overexpress hyaluronan receptors. HCNPs were prepared by mixing cisplatin with a hyaluronan solution, followed by dialysis to remove trace elements. The cells treated with HCNPs showed significantly lower viability than those treated with cisplatin alone. HCNPs were entrapped in Eudragit S100-coated pectinate/alginate microbeads (PAMs) by using an electrospray method and a polyelectrolyte multilayer-coating technique in aqueous solution. The release profile of HCNPs from Eudragit S100-coated HCNP-PAMs was pH-dependent. The percentage of 24-hour drug release was approximately 25.1% and 39.7% in pH 1.2 and pH 4.5 media, respectively. However, the percentage of drug released quickly rose to 75.6% at pH 7.4. Moreover, the result of an in vivo nephrotoxicity study demonstrated that Eudragit S100-coated HCNP-PAMs treatment could mitigate the nephrotoxicity that resulted from cisplatin. From these results, it can be concluded that Eudragit S100-coated HCNP-PAMs are promising carriers for colonspecific drug delivery.

In vitro evaluation of Moringa oleifera gum for colon- specific drug delivery

Background:Moringa gum obtained from stem of the plant Moringa oleifera Lam. belonging to family Moringaceae. Number of naturally occurring polysaccharides obtained from plant (guar gum, inulin), animal (chitosan, chondrotin sulphate), algal (alginates) or microbial (dextran) origin.Objective:The present study was evaluated Moringa oleifera gum as a carrier for colon specific drug delivery using in vitro drug release studies.Materials and Methods:Six formulations of curcumin were prepared using varying concentration of Moringa oleifera gum containing 50 mg curcumin by wet granulation method. Tablets were subjected for evaluation by studying the parameter like hardness, friability, drug content uniformity and in vitro drug release study. Hardness was found to be in the range of 5.5 to 7.3 kg/cm2, the percentage friability was in the range of 0.60 to 0.89%, and tablet showed 98.99% to 99.89% of the labeled amount of curcumin indicating uniformity in drug content.Results and Discussion:In vitro drug release study was performed using simulated stomach, intestinal and colonic fluid. The susceptibility of Moringa gum to colonic bacteria was also assessed using drug release study with rat caecal contents. 30% Moringa gum containing formulation (F-3) was shown better drug released that is 90.46%, at the end of 24 h of dissolution study in the presence of rat caecal contents in comparison to 40% Moringa gum containing formulation (F-4) that was 78.03%.Conclusion:The results illustrate the usefulness of Moringa olefera gum as a potential carrier for colon-specific drug delivery.

Different approaches of katira gum formulations for colon targeting

The objective of the study is to compare the different formulations prepared by using gum, grafted gum and hydrogel of katira as a carrier for colon-specific drug delivery using in vitro methods with and without enzymes. Katira gum is naturally occurring polysaccharides containing mainly l-rhamnose and d-galactose sugar unit and small percent of d-galactouronic acid. Compared to grafted gum and hydrogel, all proportions of katira gum protect the drug from being released completely in the physiological environment of the stomach and small intestine. In vitro release studies in enzymes (Pectinex Ultra SP-L having galactouronidase activity) have demonstrated the susceptibility of katira gum to the colonic bacterial enzyme (galactouronidase activity from Pectinex Ultra SP-L) with a consequent drug release. It illustrates that katira gum, a natural polysaccharide may be suitable as a carrier for colon targeting.

Novel pectin–4-aminothiophenole conjugate microparticles for colon-specific drug delivery

Within this study metronidazole-containing microparticles based on a pectin–4-aminothiophenol (Pec–ATP) conjugate were developed and investigated regarding their potential for colon-specific drug delivery. Microparticles were produced by spray-drying and subsequent processing. Posteriorly, they were investigated regarding their disintegration behavior, particle size, drug load, release behavior and impact on viability of Caco-2 cells. Microparticles with a mean diameter of 5.16 ± 2.41 µm and a drug load of 1.15 ± 0.03% metronidazole were prepared. Disintegration studies revealed that the stability of Pec–ATP microparticles was significantly improved compared to control microparticles based on unmodified pectin. In vitro release studies without potential colonic release-inducers revealed that 34.4-fold more metronidazole is retarded in Pec–ATP microparticles within 6 h compared to control particles. It could be demonstrated that the retarded amount of metronidazole can be released rapidly under the influence of pectinolytic enzymes or a reducing agent, simulating the colonic environment. Cell viability studies did not reveal a significant difference between native and modified pectin, neither as a solution nor as microparticle suspension. From the improved stability, the described release features and the low toxicity of the investigated microparticles can be concluded that these particles are a promising carrier for colon-specific drug delivery.

Synthesis and characterization of superparamagnetic chitosan–dextran sulfate hydrogels as nano carriers for colon-specific drug delivery

The purpose of this study was to examine chitosan (CS)–dextran sulfate (DS) nanoparticles coated iron oxide as drug carriers detectable using magnetic resonance imaging (MRI) technique. The 5-aminosalicylic acid (5-ASA) was chosen as model drug molecule. CS–DS hydrogels were formulated by a complex coacervation process under mild conditions. The influence of process variables, including the two ionic polymers, on particle size, and hydrogel entrapment of 5-ASA was studied. The in vitro release of 5-ASA were also evaluated, and the integrity of 5-ASA in the release fraction was assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The release of 5-ASA from hydrogel was based on the ion-exchange mechanism. The CS–DS hydrogel developed based on the modulation of ratio show promise as a system for controlled delivery of drug detectable using magnetic resonance imaging (MRI) technique.

PH-sensitive cationic guar gum/poly (acrylic acid) polyelectrolyte hydrogels: Swelling and in vitro drug release

Novel polyelectrolyte hydrogels (coded as GA) based on cationic guar gum (CGG) and acrylic acid monomer by photoinitiated free-radical polymerization were synthesized with various feed compositions. Fourier transform infrared spectra (FTIR), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) confirmed that the formation of the polyelectrolyte hydrogels was attributed to the strong electrostatic interaction between cationic groups in CGG and anionic groups in poly (acrylic acid) (PAA). Swelling experiments provided important information on drug diffusion properties, which indicated the GA hydrogels were highly sensitive to pH environments. Potential applications of the hydrogels matrices in controlled drug delivery were also examined. The ketoprofen-loaded CGG/PAA matrices were prepared by hydrogels and directly compressed tablets, respectively. Release behavior of ketoprofen relied on the preparative methods of matrices, ratios of CGG/AA and pH environments. The release mechanism was studied by fitting experimental data to a model equation and calculating the corresponding parameters. The result showed that the kinetics of drug release from the hydrogels in pH 7.4 buffer solution was mainly non-Fickian diffusion. However, for tablets, the drug release in pH 7.4 buffer solution was mainly affected by polymer erosion. The pH of the dissolution medium appeared to have a strong effect on the drug transport mechanism. At more basic pH values, Case II transport was observed, indicating a drug release mechanism highly influenced by macromolecular chain relaxation. The ketoprofen release is also tested in the conditions chosen to simulate gastrointestinal tract conditions. The results implied that the GA hydrogels can be exploited as potential carriers for colon-specific drug delivery.

Dendrimers conjugates for colonic delivery of 5-aminosalicylic acid

The water-soluble polyamidoamine (PAMAM) dendrimer conjugates for colonic delivery of 5-aminosalicylic acid (5-ASA) were designed. The drug was bound to the dendrimer using two different spacers containing azo-bond, p-aminobenzoic acid (PABA) and p-aminohippuric acid (PAH). Incubation of PAMAM dendrimer conjugates containing PABA and PAH spacers with rat cecal contents at 37 °C gradually released 5-ASA with time and the amount of drug released was 45.6 and 57.0% of the dose in 24 h, respectively. The release of the drug from the commercial prodrug, sulfasalazine was significantly faster than both conjugates (80.2% of the dose in 6 h). No 5-ASA was detected from the incubation of dendrimer conjugates with the homogenate of the stomach or phosphate buffer, pH 1.2 and 6.8. Only a small amount of 5-ASA was found after incubation of both conjugates with the homogenate of the small intestine for 12 h. It appears that this PAMAM dendrimer can be developed for use as a carrier for colon-specific drug delivery.

Insolubilization of sodium chondroitin sulfate by forming a semi-interpenetrating polymer network with acrylic acid: A potential carrier for colon-specific drug delivery

To reduce the highly hydrophilic property of chondroitin sulfate (ChS), a semi-interpenetrating polymer network (semi-IPN) of chondroitin sulfate/polyacrylic acid (PAA) was prepared as a drug carrier by crosslinking acrylic acid with diethyleneglycol diacrylate. The swelling properties of the semi-IPNs with different concentrations of crosslinking agent were correlated. The moisture sorption profiles were evaluated using differential thermal analysis. Ketoprofen was used as a drug probe to evaluate the performance of the drug released from the semi-IPN matrices. The prepared semi-IPNs demonstrated significant swelling reduction properties with both gastric and intestinal fluids compared with those of both the pure ChS and the ChSAA blend without the crosslinking agent. The amount of accumulated drug released from the semi-IPNs was less than 30 wt % at pH 1.2 and up to 80 wt % at pH 7.4. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 114–122, 2002

Gamma scintigraphic studies on guar gum matrix tablets for colonic drug delivery in healthy human volunteers

A novel colon-specific drug delivery system based on a polysaccharide, guar gum, was evaluated by conducting gamma scintigraphic studies using technetium-99m-DTPA as tracer, in six healthy male human volunteers. Scintigraphs taken at regular intervals have shown that some amount of tracer present on the surface of the tablets was released in stomach and small intestine and the bulk of the tracer present in the tablet mass was delivered to the colon. The colonic arrival time of the tablets was found to be 2 to 4 h. On entering the colon, the tablets were found to be degraded in five out of six volunteers thereby releasing a larger amount of the tracer. The study clearly demonstrates that guar gum, in the form of directly compressed matrix tablets, is a potential carrier for colon-specific drug delivery.