• Macromolecular Research
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• v.11 no.4
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• pp.207-223
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• 2003

For last five years, we are developing the novel local drug delivery devices using biodegradable polymers, especially polylactide (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) due to its relatively good biocompatibility, easily controlled biodegradability, good processability and only FDA approved synthetic degradable polymers. The relationship between various kinds of drug [water soluble small molecule drugs: gentamicin sulfate (GS), fentanyl citrate (FC), BCNU, azidothymidine (AZT), pamidronate (ADP), $1,25(OH)_2$ vitamin $D_3$, water insoluble small molecule drugs: fentanyl, ipriflavone (IP) and nifedipine, and water soluble large peptide molecule drug: nerve growth factor (NGF), and Japanese encephalitis virus (JEV)], different types of geometrical devices [microspheres (MSs), microcapsule, nanoparticle, wafers, pellet, beads, multiple-layered beads, implants, fiber, scaffolds, and films], and pharmacological activity are proposed and discussed for the application of pharmaceutics and tissue engineering. Also, local drug delivery devices proposed in this work are introduced in view of preparation method, drug release behavior, biocompatibility, pharmacological effect, and animal studies. In conclusion, we can control the drug release profiles varying with the preparation, formulation and geometrical parameters. Moreover, any types of drug were successfully applicable to achieve linear sustained release from short period ($1{\sim}3$ days) to long period (over 2 months). It is very important to design a suitable formulation for the wanting period of bioactive molecules loaded in biodegradable polymers for the local delivery of drug. The drug release is affected by many factors such as hydrophilicity of drug, electric charge of drug, drug loading amount, polymer molecular weight, the monomer composition, the size of implants, the applied fabrication techniques, and so on. It is well known that the commercialization of new drug needs a lot of cost of money (average: over 10 million US dollar per one drug) and time (average: above 9 years) whereas the development of DDS and high effective generic drug might be need relatively low investment with a short time period. Also, one core technology of DDS can be applicable to many drugs for the market needs. From these reasons, the DDS research on potent generic drugs might be suitable for less risk and high return.

• Polymer(Korea)
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• v.32 no.4
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• pp.322-327
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• 2008

In this study, a multi-layered pellet was composed of a seed layer including a water-swellable agent and a drug layer containing doxazosin as a model drug, a porous membrane and a castor oil layer to control drug release. The pellet is prepared by a fluidized bed coating method. To confirm drug release from polymer blending in multi-layered pellet system, it is prepared by containing different ratio such as hydroxypropylmethylcellulose (HPMC) : ethyl cellulose (EC) in drug layer and cellulose acetate(CA) : Eudragit RS in membrane. Also, to confirm the effect of oil in drug release, castor oil is coated. As a result, we observed regularly spherical pellet with diameter of $1500{\mu}m$. Release pattern of drug is confirmed by dissolution tester in aqueous media. The more the ratio of EC in drug layer, CA in membrane, and castor oil layer in pellet, the less the drug release is observed. Formation and the amount of pores in membrane is observed by SEM.

• Journal of Biomedical Engineering Research
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• v.28 no.4
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• pp.484-493
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• 2007

Two polymeric prodrugs of PGE1 (prodrugs IVg and PNg) were newly synthesized. The drug conjugation proceeded in quantitative yield without decomposition of PGE1 to PGA1. With two types conjugates, PEG-PGE1 and PN-PGE1 with different spacer groups, we first discovered a possibility of slow release of PGE1 in blood circulatory system. PGE1 is conjugated with PEG and PN through the long alkylene spacers, and their availability as polymeric prodrugs is evaluated. Their drug-releasing behavior was examined both in phosphate buffer (pH=7.4) and rat plasma. Each prodrug was known to be highly stabile in the buffer solution. The drug-releasing rate became much faster in rat plasma than in the buffer solution due to the acceleration by the plasma enzymes. The drug-release was found to reach a plateau in rat plasma because the released PGE1 or its derivatives may be captured or decomposed by the plasma proteins. The slower drug-releasing rate of pro drug PNg in rat plasma is reasonably attributed to the molecular aggregation due to the hydrophobic bonding between the PGE1 moieties and spacers.

• Journal of Pharmaceutical Investigation
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• v.36 no.3
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• pp.175-184
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• 2006

Poly(D,L-lacic acid)(PLA) microshperes containing loazepam were prepared by a solvent-emulsion evaporation method and their release patterns were investigated in vitro. Various batches of microspheres with different size and drug content were obtained by changing the ratio of lorazepam to PLA, PLA concentration in the dispersed phase and stirring rate. Rod-like lorazepam crystals on microsphere surface, which were released rapidly and could act as a loading dose, were observed with increasing drug content. The release rate was increased with increase in drug contents and decrease in the molecular weight of PLA. The release rate of lorazepam for long-acting injectable delivery system in vitro, which would aid in Predicting in vivo release Profile, could be controlled by properly optimizing various factors affecting characteristics of microspheres.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.211-217
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• 1992

Stabilization of liposomes against degradation by bile salts has been investigated in order to develop a liposomal model system for oral drug delivery. Two polysaccharides, amylopectin (AP) and chitin (CT), were employed to coat both empty liposomes and bromthymol blue (BTB)-encapsulated liposomes by adsorption-coating techniques. Turbidity changes and BTB-release characteristics in pH 5.6 buffer solutions with or without bile salts, sodium cholate and sodium glycocholate, were observed to compare the differences between uncoated liposomes and polysaccharide-coated liposomes. Initial turbidities of both uncoated and polysaccharide-coated liposomes in buffer solution were kept constant within 3% range during 4 hours of experiments. But they were decreased in a different manner in bile salts-containing buffer solutions, showing 10% or less decrease for polysaccharide-coated liposomes and 25% or more decrease for uncoated liposomes. BTB release from uncoated liposomes has been greatly increased upto 90% after 4 hours in bile salts-containing buffer solution, which is a clue for breakdown of liposomal vesicles. However, polysaccharide-coated liposomes showed the controlled-release pattern which is proportional to square-root of time, followed by around 50% release for the same time period. Consequently, it is possible to conclude that these polysaccharide-coated liposomes might be an available system for oral delivery of a drug which is unstable in gut environment.

• 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.

• Carbon letters
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• v.10 no.1
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• pp.33-37
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• 2009

Activated carbon (AC) is one of the most effective adsorbents for organic compounds because of their extended surface area, high adsorption capacity, microporous structure and special surface reactivity. The composites of pH-sensitive hydrogel and activated carbon were prepared in order to improve the loading capacity of drug. The pH-sensitive hydrogel matrix swelled well in the basic condition to release the drug loaded in AC. The release of drug was controlled depending on both the pH due to the ionization of the carboxylic acid group and the AC due to the surface properties.

• Journal of Pharmaceutical Investigation
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• v.25 no.2
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• pp.153-161
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• 1995

Alginic acid is a hydrophilic , colloidal polysaccharide obtained from cell wall of seaweed or brown algae and has a broad range of applications. Alginlc acid becomes alginate gel bead due to its cation-induced gelation. Dried alginate beads can be reswollen according to environmental pH. The purpose of this paper is to explore the possible applicability of alginate beads as an oral controlled release system of ibuprofen. In this experiment ibuprofen was incorporated in alginate beads and alginate beads were treated with various methods. Ibuprofen release from alginate beads in phosphate buffer (pH 7.4) was laster than in distilled water and dilute HCl. The release of ibuprofen was more sustained in bead than simple mixture and coprecipitate of ibuprofen and sodium alginate. The dissolution rate of ibuprofen was decreased in using of bead that hardened with formaldehyde. The dissolution rate of the drug from the bead was the fastest in 12 hour dried beads, 1.5%-sodium alginate concentration and 1%-calcium chloride concentration. Sodium alginate bead can be used as a sustaind release drug delivery system of water-insoluble drugs.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.964-968
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• 2002

Colon drug delivery is advantageous in the treatment of colonic disease and oral delivery of drugs unstable or suceptible to enzymatic degradation in upper GI tract. In this study, multilayer coated system that is resistant to gastric and small intestinal conditions but can be easily degraded by colonic bacterial enzymes was designed to achieve effective colon delivery of prednisolone. Variously coated tablets containing prednisolone were fabricated using chitosan and cellulose acetate phthalate (CAP) as coating materials. Release aspects of prednisolone in simulated gastrointestinal fluid and rat colonic extracts (CERM) were investigated. Also, colonic bacterial degradation study of chitosan was performed in CERM. From these results, a three layer (CAP/Chitosan/CAP) coated system exhibited gastric and small intestinal resistance to the release of prednisolone in vitro most effectively. The rapid increase of prednisolone in CERM was revealed as due to the degradation of the chitosan membrane by bacterial enzymes. The designed system could be used potentially used as a carrier for colon delivery of prednisolone by regulating drug release in stomach and the small intestine.

• 한국생물공학회:학술대회논문집
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• 2005.04a
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• pp.580-583
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• 2005

The aim of this study was to prepare a hydrogels composed of alginate blended with a carboxymethyl scleroglucan (CMSC) and evaluate the feasibility of the hydrogels as a drug delivery system for a protein. The main advantage of the alginate/CMSC hydrogels is to improve a restricted drug release from alginate hydrogels. The CMSC was chemically synthesized with chloroacetic acid and confirmed using a FT-IR. The alginate/CMSC hydrogels were prepared at distinct compositions by crosslinking with calcium ions. The swelling ratios of these hydrogels increased significantly with increasing the content of CMSC. At pH 7.4, the swelling ratios of the hydrogels increased remarkably as compared to those at pH 1.2. In ovalbumin (OVA) release test, the amount of OVA released from the hydrogels showed higher as compared to those released at pH 1.2. In addition, the release of OVA was improved with increasing the content of CMSC. Thus, the alginate/CMSC hydrogels may be used as a potential system for oral delivery of protein drugs.