• Journal of Pharmaceutical Investigation
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• v.22 no.4
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• pp.251-266
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• 1992

A major problem with the peptide-based drugs is that these drugs must generally be administered by injection. Therefore, there is considerable research interest in alternative routes of delivery, such as buccal, nasal, gastrointestinal route and etc. Site-specific drug delivery to the colon, as an alternative to parenteral drug delivery, is of interest for the delivery of peptide-based drugs as well as the delivery of low molecular weight drugs for the treatment of colonic disease, This review describes some considerations of colon-specific drug delivery using hydrogels.

• Biotechnology and Bioprocess Engineering:BBE
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• v.9 no.3
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• pp.191-195
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• 2004

Drug delivery systems that are based on pectin have been studied for colon specific delivery using the specific activity of colon microflora. The aim of this study was to design a novel method of manufacturing pectin microspheres without oils and surfactants and to investigate the potential use of the pectin microspheres as an oral colon-specific drug carrier. The pectin microspheres were successfully formed using the spray drying method and crosslinking with calcium chloride. From the crosslinked pectin microspheres, indomethacin (IND) release was more suppressed than its release from non-crosslinked microspheres. In a low pH (pH 1.4) environment, the pectin microspheres released IND at an amount of about 18${\pm}$2% of the total loaded weight for 24 h while the release rate of IND was stimulated at neutral pH (pH 7.4). IND release from the pectin microspheres was increased by the addition of pectinase. The results clearly demonstrate that the pectin microspheres that were prepared by the spray drying and crosslinking methods are potential carriers for colon-specific drug deliveries.

• Archives of Pharmacal Research
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• v.28 no.8
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• pp.983-987
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• 2005

Hydrogels composed of glycidyl methacrylate dextran (GMD) and poly(acrylic acid, PM) were prepared by UV irradiation method for colon-specific drug delivery. GMD was synthesized by coupling of glycidyl methacrylate to dextran in the presence of 4-(N,N-dimethylamino)pyridine. GMD was photo-polymerized by ammonium peroxydisulfate as initiating system in phosphate­buffered solution (0.1 M, pH 7.4). And then, acrylic acid monomer was added and subsequently heat-polymerized by 2,2'-azobisisobutyronitrile as an initiator. The hydrogels exhibited high swelling ratio (about 20) at $37^{\circ}C$, and showed a pH-dependent swelling behavior. In addition, the swelling ratio of the hydrogel was remarkably enhanced to about 45 times in the presence of dextranase at pH 7.4. The swelling-deswelling behavior proceeded reversibly for the GMD/PM hydrogels between pH 2 and pH 7.4. Release of 5-aminosalicylic acid from the GMD/PAA hydrogels was evaluated in simulated gastrointestinal pH fluids in the absence or presence of dextranase. We concluded that the hydrogels prepared could be used as a dual-sensitive drug carrier for sequential release in gastrointestinal tract.

• Archives of Pharmacal Research
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• v.24 no.1
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• pp.69-73
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• 2001

Biodegradable hydrogels based on glycidyl methacrylate dextran (CMD) and dimethacrylate poly(ethylene glycol) (DMP) were proposed for colon-specific drug delivery. GMD was synthesized by coupling of glycidyl methacylate with dextran in the presence of 4-(N, N-dimethylamino)pyridine (DMAP) using dimethylsulfoxide as a solvent. Methacrylate-terminated poly (ethylene glycol) (PEG) macromer was prepared by the reaction of PEG with methacryloyl chloride. CMD/DMP hydrogels were prepared by radical polymerization of phosphate buffer solution (0.1 M, pH 7.4) of GMD and DMP using ammonium peroxydisulfate (APS) and UV as initiating system. The synthetic GMD, DMP and GMD/DMP hydrogels were characterized by fourier transform infrared (FT-lR) spectroscopy. The FITC-albumin loaded hydrogels were prepared by adding FITC-albumin solution before UV irradiation. Swelling capacity of GMD/DMP hydrogels was controlled not only by molecular weight of dextran, but also by incorporation ratio of DMP Degradation of the hydrogels has been studied in vitro with dextranase. FITC-albumin release from the GMD/DMP hydrogels was affected by molecular weight of nextran and the presence of dextranase in the release medium.

• Macromolecular Research
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• v.17 no.9
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• pp.709-713
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• 2009

The aim of this study was to develop novel intestinal specific drug delivery systems with pH sensitive swelling and drug release properties. The carboxyl group of ibuprofen was converted to a vinyl ester group by reacting ibuprofen and vinyl acetate as an acylating agent in the presence of catalyst. The glucose-6-acrylate-1, 2, 3, 4-tetraacetate (GATA) monomer was prepared under mild conditions. Cubane-1, 4-dicarboxylic acid (CDA) linked to two 2-hydroxyethyl methacrylate (HEMA) group was used as the crosslinking agent (CA). Methacrylic-type polymeric prodrugs were synthesized by the free radical copolymerization of methacrylic acid, vinyl ester derivative of ibuprofen (VIP) and GATA in the presence of cubane cross linking agent. The structure of VIP was characterized and confirmed by FTIR, $^1H$ NMR and $^{13}C$ NMR spectroscopy. The composition of the cross-linked three-dimensional polymers was determined by FTIR spectroscopy. The hydrolysis of drug polymer conjugates was carried out in cel-lophane membrane dialysis bags, and the in vitro release profiles were established separately in enzyme-free simulated gastric and intestinal fluids (SGF, pH 1 and SIF, pH 7.4). The detection of a hydrolysis solution by UV spectroscopy at selected intervals showed that the drug can be released by hydrolysis of the ester bond between the drug and polymer backbone at a low rate. Drug release studies showed that increasing the MAA content in the copolymer enhances the rate of hydrolysis in SIP. These results suggest that these polymeric prodrugs can be useful for the release of ibuprofen in controlled release systems.

• Macromolecular Research
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• v.11 no.4
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• pp.291-295
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• 2003

Dextran as a candidate material for colon-specific drug delivery has been studied. Crosslinked dextran hydrogels were prepared by mixing dextran, $MgCl_2$, glutaraldehyde (GA) and polyethyleneglycol (PEG 400) in water. The dextran hydrogels were characterized by measuring equilibrium swelling ratios and mechanical strengths. Response surface methodology (Central Composite Design) was used to evaluate the swelling behaviors and mechanical strengths as functions of concentrations of $MgCl_2$, GA, and PEG 400, which was found to be useful for the evaluation. It showed that the swelling behavior and mechanical strengths were influenced significantly by PEG 400 and $MgCl_2$ concentrations.

• Macromolecular Research
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• v.14 no.1
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• pp.66-72
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• 2006

The purpose of this study is to develop novel nanoparticles based on polyion complex formation between low molecular weight water-soluble chitosan (LMWSC) and all-trans retinoic acid (atRA). LMWSC nanoparticles encapsulating atRA based on polyion complex were prepared by mixing of atRA into LMWSC aqueous solution using ultrasonication. In FTIR spectra, the carbonyl group of atRA at 1690 $cm^{-1}$ disappeared or decreased when ion complexes were formed between LMWSC and atRA. In ${1}^H$ NMR spectra, specific peaks of atRA disappeared when atRA-encapsulated LMWSC (RAC) nanoparticles were reconstituted into $D_{2}O$ while specific peaks both of atRA and LMWSC appeared in $D_{2}O$/DMSO (1/3, v/v) mixture. XRD patterns also showed that the crystal peaks of atRA were disappeared by encapsulation into LMWSC nanoparticles. LMWSC nanoparticles encapsulating atRA have spherical shapes with particle size below 200 nm. The mechanism of encapsulation of atRA into LMWSC nanoparticles was thought to be an ion complex formation between LMWSC and atRA. LMWSC nanoparticles showed high atRA loading efficiency over 90$\%$ (w/w). AtRA was continuously released from nanoparticles over 10 days. In in vitro cell cytotoxicity test, free atRA showed higher cytotoxic effect against CT 26 colon carcinoma cell line on 1 day. However, RAC nanoparticles showed similar cytotoxicity against CT 26 cells on 2 day. These results suggest the potential for the introduction of LMWSC nanoparticles into various biomedical fields such as drug delivery.