• Journal of Pharmaceutical Investigation
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• v.21 no.4
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• pp.253-262
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• 1991

Microencapsulation of sodium ascorbate with cellulose acetate phthalate(CAP) by coacervation/ phase separation method were carried out. Various factors affecting microencapsulation, i.e., surfactant concentration. CAP concentration, stirring speed and treatment of spermaceti as a sealing agent were studied. Dissolution rate. particle size distribution, surface feature and stability test were investigated. CAP microcapsules prepared using 0.5% span 80 as a surfactant showed smooth and round surfaces. The release of sodium ascorbate was retarded by microencapsulation with CAP and by sealant treatment with spermaceti. When triturated with sodium bicarbonate, CAP microcapsules were more stable than unencapsulated sodium ascorbate under various RH conditions at $37^{\circ}C$.

• Journal of Pharmaceutical Investigation
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• v.19 no.4
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• pp.195-202
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• 1989

In attempt to improve the chemotherapeutic activity of adriamycin, adriamycin-entrapped HSA microspheres were prepared and investigated by the various in vitro experiments. The shape, surface characteristics and size distribution of HSA microspheres are observed by scanning electron microscopy. The in vitro drug release, albumin matrix degradation by protease of HSA microspheres were studied. The shape of HSA microspheres were spherical and the surface was smooth and compact. The size of HSA microspheres ranged from 0.4 to $2.5\;{\mu}m$ and have average diameters of 0.5 to $0.7\;{\mu}m$. The size distribution of HSA microspheres prepared by ultrasonication was mainly affected by albumin concentration and heating time in the process of hardening. In in vitro, almost all adriamycin was released from HSA microspheres for 8 hr. Analysis of the resulting adriamycin release profiles demonstrated that adriamycin is released from the microspheres in two distinct steps, a fast phase (until 30 min) followed by a much slower sustained release phase. Drug release, which is due to diffusion, was depended on the rate of matrix hydration. Drug release was largely affected by albumin concentration and heating temperature during the process of hardening. Albumin matrix degradation of HSA microspheres was affected by heating temperature and albumin concentration. Higher temperature and longer times generally produce harder, less porous, and slowly degradable microspheres.

• Polymer(Korea)
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• v.25 no.6
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• pp.884-892
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• 2001

Biodegradable wafers were prepared with poly (L-lactide-co-glycolide) (50 : 50 mole ratio of lactide to glycolide, molecular weight:5000 g/mole) by direct compression method for the sustained release of nifedipine to investigate the possibility of the treatment of hypertension. PLGA wafers were prepared by altering initial drug/polymer loading ratio, wafer thickness, and hydroxypropyl methylcellulose (HPMC) content. These wafers showed new zero-order release patterns for 11 days, and various biphasic release patterns could be obtained by altering the composition of wafers such as addition of matrix binder as HPMC to the PLGA wafer to reduce release rate of initial phase. The onset of polymer mass loss only occured after 4 days and about 40% of mass loss was observed after 11 days nifedipine release. This system had advantages in terms of simplicity in design and obviousness of drug release rate and may be useful as an implantable dosage form.

• Bulletin of the Korean Chemical Society
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• v.32 no.3
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• pp.867-872
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• 2011

For the prolonged delivery and sustained release rates of low molecular weight drugs, poly(lactic-co-glycolic acid) (PLGA) microparticles containing the drug SKL-2020 have been investigated. On increasing polyvinyl alcohol (PVA) concentration (from 0.2% to 5%), the size of microparticles decreased (from $48.02{\mu}m$ to $10.63{\mu}m$) and more uniform size distribution was noticeable due to the powerful emulsifying ability of PVA. A higher drug loading (from 5% to 20%) caused a larger concentration gradient between 2 phases at the polymer precipitation step; this resulted in decreased encapsulation efficiency (from 34.19% to 25.67%) and a greater initial burst (from 61.71% to 70.05%). SKL-2020-loaded PLGA microparticles prepared with different fabrication conditions exhibited unique release patterns of SKL-2020. High PVA concentration and high drug loading led to an initial burst effect by rapid drug diffusion through the polymer matrix. Since PLGA microparticles enabled the slow release of SKL-2020 over 1 week in vitro and in vivo, more convenient and comfortable treatment could be facilitated with less frequent administration. It is feasible to design a release profile by mixing microparticles that were prepared with different fabrication conditions. By this method, the initial burst could be repressed properly and drug release rate could decrease.

• Journal of the Korean Chemical Society
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• v.57 no.1
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• pp.88-93
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• 2013

In order to construct a controlled release system of drugs and to reduce toxic side effects of 5-fluorouracil, the novel ramose chitosan-based-5-fluorouracil microspheres (CS-FU-MS) were prepared. Firstly, using chitosan (CS) as carriers and 5-fluorouracil (5-FU) as a model drug, ramose chitosan-based-5-fluorouracil (CS-FU) was efciently synthesized by chemical crosslinking method through microwave irradiation, drug loading was 10.6%; Secondly, CS-FU-MS were prepared by CS-FU self-assembled under the dialysis conditions and the free 5-FU was encapsulated further at the same time. The size dispersivity of particles is uniform, and the average diameter of the CS-FU-MS was $4{\mu}m$. The drug encapsulation efficiency was 76.1%, and the drug loading was increased to 26.22%. CS-FU-MS maintain the zero-order release time in PBS (pH = 7.4) and HCl/KCl (pH = 1.2) dialysis medium was 40h and 34h respectively, and the cumulative release were 58.89% and 79.33% in 182 h. The results showed that CS-FU-MS have excellent sustained release properties.

• 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.

• Polymer(Korea)
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• v.28 no.4
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• pp.291-297
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• 2004

Water-soluble chitosan micro spheres were prepared by emulsification of chitosan solution in mineral oil followed by cross linking reaction with different amount of the cross linking agent (glutraraldehyde), different chitosan concentration. Then, the physicochemical properties such as morphological change by degradation, drug loading efficiency, and drug release profiles were investigated with the drug loaded water-soluble chitosan microspheres. Norfloxacin loaded water-soluble chitosan micro spheres showed excellent drug entrapping capacities without burst release caused by surface bound drug. The absence of the surface bound drug also confirmed by X-ray diffraction study. Degradation and drug release studies showed that the amount of the crosslinking agent played a crucial role for drug loading, release and degradation. The water-soluble chitosan micro spheres showed more sustained drug release profiles with slower degradation and larger particle size by increasing crosslinking agent.

• Polymer(Korea)
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• v.26 no.5
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• pp.680-690
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• 2002

Implantable biodegradable wafers were prepared with pamidronate -loaded poly (L-lactide-co-glycolide) (PLGA, 75 : 25 mole ratio by lactide to glycolide, molecular weight : 20000 and 90000 g/mole) by direct compression method for the sustained release of pamidronate to investigate the possibility for the treatment of bone resorption. Pamidronate-loaded PLGA powders were prepared by means of physical mixing and spray drying with the control of formulation factors and characterized by scanning electron microscope and X-ray diffractometer. The pamidronate-loaded PLGA powders fabricated into wafers by direct compression under the constant pressure and time at room temperature. These wafers were also observed for their structural characteristic, release pattern, and degradation pattern. The release rate of pamidronate increased with increasing their initial loading ratio as well as increasing wafer thickness. The molecular weight of PLGA affects the release pattern : the higher molecular weight of PLGA, the faster release rate. It can be explained that the higher viscosity of high molecular PLGA solution at same concentration tends to aggregate PLGA and pamidronate resulting in unstable pharmaceutical dosage form. This system had advantages in terms of simplicity in design and obviousness of drug release rate and nay be useful as an implantable dosage form for the treatment of aural cholesteatoma.

• Animal cells and systems
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• v.3 no.2
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• pp.103-113
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• 1999

Many in-depth reviews related to regulations of prolactin secretion are available. We will, therefore, focus on controversial aspects using personal opinion in this review. The neuroendocrine control of prolactin secretion from the anterior pituitary gland involves multiple factors including prolactin-release inhibiting factor (PIF) and prolactin releasing factor (PRF). The PIF exerts a tonic inhibitory control in the physiological conditions. The PIF should be able to effectively inhibit prolactin release or a lifetime, but the inhibitory action of dopamine cannot be sustained for a long period of time. Perifusion of a high concentration of dopamine (l ,000 nM) could not sustain inhibitory action on prolactin release but when a small amount of ascorbic acid (0.1 mM) is added in a low concentration of dopamine (3 nM) solution, prolactin release was inhibited for a long period. Ascorbate is essential for dopamine action to inhibit prolactin release. We have, therefore, concluded that the PIF is dopamine plus ascorbate. The major transduction system for dopamine to inhibit prolactin release is the adenylyl cyclase system. Dopamine decreases cyclic AMP concentration by inhibiting adenylyl cyclase, and cyclic AMP stimulates prolactin release. However, the inhibitory mechanism of dopamine on prolactin release is much more complex than simple inhibition of CAMP production. The dopamine not only inhibits cyclic AMP synthesis but also inhibits prolactin release by acting on a link(s) after the CAMP event in a chain reaction for inhibiting prolactin release. Low concentrations of dopamine stimulate prolactin release. Lactotropes are made of several different subtypes of cells and several different dopamine receptors are found in pituitary. The inhibitory and stimulatory actions induced by dopamine can be generated by different subtype of receptors. The GH$_4$ZR$_7$ cells express only the short isoform (D$_{2s}$) of the dopamine receptor, as a result of transfecting the D$_{2s}$ receptors into GH$_4$C$_1$ cells which do not express any dopamine receptors. When dopamine stimulates or inhibits prolactin release in GH$_4$ZR$_7$ cells, it is clear that the dopamine should act on dopamine D$_{2s}$ receptors since there is no other dopamine receptor in the GH$_4$ZR$_7$. Dopamine is able to stimulate prolactin release in a relatively low concentration while it inhibits in a high concentration in GH$_4$ZR$_7$. These observations indicate that the dopamine D$_2$ receptor can activate stimulatory and/or inhibitory transduction system depending upon dopamine concentrations.

• Journal of Pharmaceutical Investigation
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• v.29 no.1
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• pp.21-27
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• 1999

Semi-solid poly(ortho esters) (POE) were prepared to provide bioerodible carriers for sustained drug delivery systems of naloxone (NLX) in the treatment of narcotic addiction. As the POE have viscous behavior at room temperature, a significant advantage of this polymer is that it can be injected without any surgical intervention. The POE was synthesized by a transesterification reaction between 1,2,6-hexanetriol and trimethyl orthoacetate, and the structure of the polymer was confirmed by IR. The in vitro release of the drug from POE was studied. The release rate of NLX decreased with increasing intrinsic viscosities of the polymer. In vivo biocompatibility studies were carried out in rats with NLX loaded POE. Histopathological analysis showed that NLX implants are well-tolerated by rats when used subcutaneously. Pharmacokinetic studies of POE-NLX implants of two different viscosities were carried out in rabbits. In all cases, plasma concentrations of NLX were maintained over 1 ng/ml for at least 168 hours, but initial burst effect was observed. Mean residence time(MRT) was found to depend on the viscosity of the polymer.