• Polymer(Korea)
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• v.26 no.1
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• pp.128-138
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• 2002

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU, Carmustine)-loaded poly(D, L-lactide-co-glycolide) (PLGA, lactide/glycolide mole ratio 75 : 25) microparticles were prepared and fabricated into wafers in an attempt to study the possibility for the treatment of malignant glioma by direct inserting the wafers to the tumor or the cavity remained after surgical resection of the tumor. SEM observation of the microparticles prepared by spray drying method revealed that the microparticles were spherical, i. e. microspheres. Significant reduction of the crystallinity of BCNU encapsulated in PLGA was confirmed by X-ray diffraction and differential scanning calorimetry analyses of the BCNU-loaded PLGA microparticles. Release pattern of BCNU was dependent on several preparation parameters, such as the molecular weight and concentration of PLGA, and initial BCNU loading amount, etc. In vitro release of BCNU was prolonged over 8 weeks with close to zero-order release pattern after initial burst effect. Observations of morphological change of wafers and pH change of release media during release test period confirmed that hydration and degradation of PLGA would be facilitated with an increase of BCNU-loading amount.

• Polymer(Korea)
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• v.28 no.4
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• pp.335-343
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• 2004

Carmustine (l,3-bis(2-chloroethyI)-1-nitrosourea, BICNU) used as antineoplastic drug for the treatment of brain tumor is not appropriate for the long term delivery, because it has short biological half life. Therefore, poly(D,L-lactide-co-glycolide) (PLGA) is useful as drug carrier for the long term delivery due to bulk erosion property. Glycolide monomer is applied to release of BICNU owing to non-toxic and monomeric components after biodegradation of PLGA. In this study, BICNU-loaded PLGA wafers with or without glycolide monomer were fabricated by conventional direct compression method for the sustained release of BICNU. These wafers were observed for their release profiles of BICNU and degradation rates by SEM, NMR, and GPC. Furthermore, we make multi-layer wafers and compare them with release profiles of conventional wafer. From these results, drug release of BICNU-loaded PLGA wafers was increased with increasing the glycolid monomer contents. We confirmed that glycolide monomer and BICNU contents in barrier-layer influenced the drug release profiles and degradation rate.

• Journal of Pharmaceutical Investigation
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• v.26 no.2
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• pp.137-144
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• 1996

The study was carried out for the preparation and evaluation of a buoyant hydrogel matrix (BHM), which is buoyant in a neutral or in pH 2.0 buffer solution, by the aspects of buoyancy, swelling, and drug release. Physical mixtures of HPC and CP in various molar ratio were employed as a mucoadhesive polymer which swells and controls the rate of drug release. Anhydrous citric acid and sodium bicarbonate in the molar ratio of 1:3 were employed as effervescing agents which provide a buoyancy for the mucoadhesive polymeric matrix. The buoyancy in vitro was expressed as both floating time$(T_{fl})$ and surfing time$(T_{sf})$, which are the time required for floating from the bottom to the surface of the medium and the time to keep the floated state at the surface of medium during release studies, respectively. A close relationship was observed between the buoyancy and the amount of effervescing agent added. $T_{fl}$ of the buoyant hydrogel matrices were decreased to about 10 seconds linearly with increasing the amount of effervescing agent in the range of 5 to 15%. $T_{sf}$ of the buoyant hydrogel matrices were varied from 1 to 3 hr depending on the amount of effervescing agent. The swelling was observed by changes in diameter of the buoyant hydrogel matrices in distilled water or acidic buffer solution, resulted in dependences on pH and the amount of effervescing agents. The release of hydrochlorothiazide from the buoyant hydrogel matrices were followed by apparent zero-order kinetics, while the buoyant hydrogel matrices were floated at the surface and maintaining their swollen shapes.

• Macromolecular Research
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• v.11 no.5
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• pp.334-340
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• 2003

In order to fabricate new sustained delivery device of nerve growth factor (NGF), we developed NGF-loaded biodegradable poly(L-lactide-co-glycolide) (PLGA, the mole ratio of lactide to glycolide 75:25, molecular weight: 83,000 and 43,000 g/mole, respectively) film by novel and simple sandwich solvent casting method for the possibility of the application of neural tissue engineering. PLGA was copolymerized by direct condensation reaction and the molecular weight was controlled by reaction time. Released behavior of NGF from NGF-loaded films was characterized by enzyme linked immunosorbent assay (ELISA) and degradation characteristics were observed by scanning electron microscopy (SEM) and gel permeation chromatography (GPC). The bioactivity of released NGF was identified using a rat pheochromocytoma (PC-12) cell based bioassay. The release of NGF from the NGF-loaded PLGA films was prolonged over 35 days with zero-order rate of 0.5-0.8 ng NGF/day without initial burst and could be controlled by the variations of molecular weight and NGF loading amount. After 7 days NGF released in phosphate buffered saline and PC-12 cell cultured on the NGF-loaded PLGA film for 3 days. The released NGF stimulated neurite sprouting in cultured PC-12 cells, that is to say, the remained NGF in the NGF/PLGA film at 37 $^{\circ}C$ for 7 days was still bioactive. This study suggested that NGF-loaded PLGA sandwich film is released the desired period in delivery system and useful neuronal growth culture as nerve contact guidance tube for the application of neural tissue engineering.

• Bulletin of the Korean Chemical Society
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• v.22 no.5
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• pp.467-475
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• 2001

A triblock copolymer based on $poly(\varepsilon-caprolactone)$ (PCL) as the hydrophobic part and poly(ethylene glycol) (PEG) as the hydrophilic portion was synthesized by a ring-opening mechanism of ${\varepsilon}-caprolactone$ with PEG containing a hydroxyl group at bot h ends as an initiator. The synthesized block copolymers of PCL/PEG/PCL (CEC) were confirmed and characterized using various analysis equipment such as 1H NMR, DSC, FT-IR, and WAXD. Core-shell type nanoparticles of CEC triblock copolymers were prepared using a dialysis technique to estimate their potential as a colloidal drug carrier using a hydrophobic drug. From the results of particle size analysis and transmission electron microscopy, the particle size of CEC core-shell type nanoparticles was determined to be about 20-60 nm with a spherical shape. Since CEC block copolymer nanoparticles have a core-shell type micellar structure and small particle size similar to polymeric micelles, CEC block copolymer can self-associate at certain concentrations and the critical association concentration (CAC) was able to be determined by fluorescence probe techniques. The CAC values of the CEC block copolymers were dependent on the PCL block length. In addition, drug loading contents were dependent on the PCL block length: the larger the PCL block length, the higher the drug loading content. Drug release from CEC core-shell type nanoparticles showed an initial burst release for the first 12 hrs followed by pseudo-zero order release kinetics for 2 or 3 days. CEC-2 block copolymer core-shell type nanoparticles were degraded very slowly, suggesting that the drug release kinetics were governed by a diffusion mechanism rather than a degradation mechanism irrelevant to the CEC block copolymer composition.

• Polymer(Korea)
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• v.29 no.3
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• pp.260-265
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• 2005

The initial burst of drug release is an important role in the controlled delivery of drug having hish toxicity and narrow therapeutic ranges. Nanosphere composed of monolayer could not achieve precisely controlled drug release because of the initial burst of drug on surface. In this study, double layered nanosphere was prepared for sustained drug delivery without initial burst. Double layered nanosphere composed of dextran and PLGA was fabricated by using conventional W/O/W double emulsion method. To control surface tension on the outer layer of nanospheres, PVA was used as a surfactant. Release behavior of dextran as model drug was observed as the $3{\times}1$mm wafers formed by compression mould in the deionized water for 7 days. Double layered nanosphere has sustained release behavior, in contast to single layered nanospheres. such as mechanical mixture and dextran nanospheres. Especially, nanosphere containing PVA $0.2\%$ has shown nearly the zero-order release profile. As a result of this study, double layered nanospheres has more sustained release profile of drug without the initial burst and the release behavior of dexoan on tile double layered nanospheres was controlled by the contents of PVA as a surfactant.

• Polymer(Korea)
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• v.29 no.5
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• pp.468-474
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• 2005

PLGA and PCL copolymers initiated by carbitol as drug carriers were synthesized by ring-opening polymerization of L-lactide (LA), glycolide (GA), and $\varepsilon-caprolactone(\varepsilon-CL)$. Implantable wafers were simply fabricated by direct compression method after physical mixing of copolymers and bovine serum albumin-fluorescein isothiocyanate (BSA-FITC) as a model protein drug. The release amounts of BSA-FITC from wafers were determined by fluorescence intensity using the fluorescence spectrophotometer. Also, the release behavior of BSA-FITC on wafers was controlled by adding the additives such as collagen, small intestinal submucosa (SIS), poly(vinyl pyrrolidone) (PVP), and poly(thylene glycol) (PEG). The wafer prepared by PLGA and PCL exhibited slow release within $10\%$ for 30 days. But, those prepared by a variety of additives exhibited the controlled BSA release patterns with a dependence on the additive contents. furthermore, the wafers containing natural materials such as collagen and SIS showed more zero-order release profile than that with synthetic materials such as PVP and PEG. It was confirmed that the release of BSA from implantable wafers could be easily controlled by adding natural additives.

• Journal of Korean Society of Water and Wastewater
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• v.21 no.6
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• pp.679-687
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• 2007

Nanoscale zero valent ion (nZVI) technology is emerging as an innovative method to treat contaminated groundwater. The activity of nZVI is very high due to their high specific surface area, and supporting this material can help to preserve its chemical nature by inhibiting oxidation. In this study, nZVI particles were attached to granular ion-exchange resin through borohydride reduction of ferrous ions, and chemical reduction of nitrate by this material was investigated as a potential technology to remove nitrate from groundwater. The pore structure and physical characteristics were measured and the change by the adsorption of nZVI was discussed. Batch tests were conducted to characterize the activity of the supported nZVI and the results indicated that the degradation of nitrate appeared to be a pseudo first-order reaction with the observed reaction rate constant of $0.425h^{-1}$ without pH control. The reduction process continued but at a much lower rate with a rate constant of $0.044h^{-1}$, which is likely limited by mass transfer. To assess the effects of other ions commonly found in groundwater, the same experiments were conducted in simulated groundwater with the same level of nitrate. In simulated groundwater, the rate constant was $0.078h^{-1}$ and it also reduced to $0.0021h^{-1}$ in later phase. The major limitation in application of ZVI for nitrate reduction is ammonium production. By using a support material with ion exchange capacity, the problem of ammonium release can be solved. The ammonium was not detected in the batch test, even when other competitive ions such as calcium and potassium existed.

• Journal of Pharmaceutical Investigation
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• v.19 no.2
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• pp.87-92
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• 1989

The multilayered monolithic type transdermal delivery device has been designed and analyzed by a numerical analysis. The device consists of three layered polymer matrices which posess the different diffusion parameters, respectively. The purpose of this study was to design an ideal transdermal drug delivery device which is capable of initial burst and zero order release later on. Numerical modelings were simulated for a dispersed and a dissolved multilayered monolithic system. The results showed that the dispersed multilayered monolithic system could meet the requirements for an ideal transdermal delivery device.

• Archives of Pharmacal Research
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• v.26 no.8
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• pp.649-652
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• 2003

Polymeric nanoparticles composed of polystyrene (PS) as core and poly(methacrylic acid) (PMA) as corona were prepared by the dispersion copolymerization. The potential of the nanoparticles as carriers for recombinant human epidermal growth factor (EGF) was investigated. The nanoparticles showed monodispersity and good water-dispersibility. The loading content of EGF to the nanoparticles was very high due to electrostatic interaction between EGF and nanoparticles. EGF was released as a pseudo-zero order pattern after initial burst effect. The nanoparticles were sufficient for A431 cells proliferation.