• Macromolecular Research
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• v.13 no.5
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• pp.397-402
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• 2005

To explore the potential of shell crosslinked micelle (SCM) as a drug carrier, the drug release behavior of poly($\varepsilon$-caprolactone)-b-poly(acrylic acid) (PCL-b-PAA) SCMs was investigated. PCL-b-PAA was synthesized by ring opening polymerization of $\varepsilon$-caprolactone and atom transfer radical polymerization of tert-butyl acrylate, followed by selective hydrolysis of tert-butyl ester groups to acrylic acid groups. The resulting amphiphilic polymer was used to prepare SCMs by crosslinking of PAA corona via amidation chemistry. The drug release behavior of the SCMs was studied, using pyrene as a model drug, and was compared with that of non-crosslinked micelles, especially below the critical micelle concentration (CMC). When the shell layers were crosslinked, the drug release behavior of the SCMs was successfully modulated at a controlled rate compared with that of the non-crosslinked micelles, which showed a burst release of drug within a short time.

• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.445-451
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• 2005

As a selective ${\alpha}_{1A}-adrenoreceptor$ antagonist, tamsulosin has been used clinically for urinary obstructed patients with benign prostatic hyperplasia. The single and multi-layered pellets containing tamsulosin hydrochloride were prepared in an effort to control the drug release, avoiding dose-dependent side effects of tamsulosin hydrochloride upon oral administration. The drug release from multi-layered pellets was substantially controlled, compared with single layered pellets. The drug release from coated pellets with single or multi layer was affected by the nature of coating agent, the percentage of coating level and the presence of hydrophilic material in coating layer. In conclusion, the controlled release oral delivery system using multi-layered pellet is very useful for tamsulosin hydrochloride, resulting in improvement of patient compliance and therapeutic drug levels for a longer period of time.

• KSBB Journal
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• v.10 no.4
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• pp.428-434
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• 1995

Target-sensitive(TG-S) liposomes, which have the antibodies coupled on the surface of liposome and can release their entrapped contents by the binding of antibodies with the specigic target cells, were prepared and employed to study the release of calcein and the selective delivery of an anticancer agent, doxorubicin(DOX). The monoclonal antibody, Y3, used for the preparation of the TG-S liposome was one against major histocompatibility complex class 1 of mouse(MHCI, H-2Kｂtype) and the target cells were EL-4 and RMA, which have the MHC1, H-2Kbtype on their membrane surfacem. The release of calcein from TG-S liposome occurred when the target cells were contacted with liposomes and it was proportionally increased with the rise of binding capacity of antibody coupled on the surface of liposome to the target cells. The experimental results of drug delivery were similar to the cases of calcein release. The viability of specific target cell, EL-4 with liposomal DOX was not so different from that with the free DOX, while for the non-specific target cell, Yacl(H-2Kf), the cell viability with Iiposomal DOX was much higher than that with free DOX. This shows the fact that the liposomal DOX can be efficiently delivered to the specific target cells, while it was not the case for the non-specific target cells. And the drug delivery was lnhibited when the free antibody of Y3 was added in the contact process between EL-4 and TG-S liposomes, which means the drug delivery occurred mainly by the destabilization of TG-S liposomes. From these results, we could conclude that the selective drug delivery to specific target cell using the TG-S liposome would be feasible.

• Applied Chemistry for Engineering
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• v.29 no.2
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• pp.147-154
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• 2018

Currently, to overcome low therapeutic efficiencies and side effects of anticancer agents, the study of drug carrier based on polymers have been consistently investigated. Although the traditional drug carrier based on polymers displayed an excellent result and significant progress, there has been a problem with the side effect and low therapeutic efficiency because of the premature drug release before reached to the targeted region by the low stability in blood stream and sustained drug release. In this review article, to improve the problem of inefficient drug release, methods were suggested, which can maximize the therapeutic efficiency by increasing the stability in the blood stream and triggering drug release at the target site by introducing a stimuli-responsive substance to the non-toxic and biocompatible natural polymer chitosan.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.1
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• pp.31-39
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• 1998

As it has been reported that the depolarization induced acetylcholine (ACh) release is modulated by activation of presynaptic $A_1$ adenosine heteroreceptor and various lines of evidence suggest the $A_2$ adenosine receptor is present in the hippocampus. The present study was undertaken to delineate the role of adenosine receptors on the hippocampal ACh release. Slices from the rat hippocampus were equilibrated with $[^3H]choline$ and then the release amount of the labelled product, $[^3H]ACh$, which was evoked by electrical stimulation (rectangular pulses, 3 Hz, 2 ms, 24 mA, $5\;V/cm^{-1}$, 2 min), was measured, and the influence of various adenosine receptor-related agents on the evoked tritium outflow was investigated. And also, the drug-receptor binding assay was performed in order to confirm the presence of $A_1$ and $A_2$ adenosine receptors in the rat hippocampus. N-ethylcarboxamidoadenosine (NECA), a potent adenosine receptor agonist with nearly equal affinity at $A_1$ and $A_2$ adenosine receptors, in concentrations ranging from $1{\sim}30\;{\mu}M$, decreased the electrically-evoked $[^3H]ACh$ release in a concentration-dependent manner without affecting the basal rate of release. And the effect of NECA was significantly inhibited by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 2 ${\mu}M$), a selective $A_1$ adenosine receptor antagonist, but was not influenced by 3,7-dimethyl-1-propargylxanthine (DMPX, 5 ${\mu}M$), a specific $A_2$ adenosine receptor antagonist. $N^6-cyclopentyladenosine$ (CPA), a selective $A_1$ adenosine receptor agonist, in doses ranging from 0.1 to 10 ${\mu}M$, reduced evoked $[^3H]ACh$ release in a dose-dependent manner without the change of the basal release. And the effect of CPA was significantly inhibited by 2 ${\mu}M$ DPCPX treatment. 2-P-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS-21680C), a potent $A_2$ adenosine receptor agonist, in concentrations ranging from 0.1 to 10 ${\mu}M$, did not alter the evoked ACh release. In the drug-receptor binding assay, the binding of $[^3H]2-chloro-N^6-cyclopentyladenosine$ ($[^3H]$CCPA) to the $A_1$ adenosine receptor of rat hippocampal membranes was inhibited by CPA ($K_i$ = 1.22 nM), NECA ($K_i=10.17 nM$) and DPCPX ($K_i=161.86 nM$), but not by CGS-21680C ($K_i=2,380 nM$) and DMPX ($K_i=22,367 nM$). However, the specific binding of $[^3H]CGS-21680C$ to the $A_2$ adenosine receptor was not observed. These results suggest that the $A_1$ adenosine heteroreceptor play an important role in evoked ACh release, but the presence of $A_2$ adenosine receptor is not confirmed in this study.

• Macromolecular Research
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• v.15 no.7
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• pp.646-655
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• 2007

To achieve targeted drug delivery for chemotherapy, a ligand-mediated nanoparticulate drug carrier was designed, which could identity a specific receptor on the surfaces of tumor cells. Biodegradable poly(ethylene oxide)/poly$({\varepsilon}-caprolactone)$ (PEG/PCL) amphiphilic block copolymers coupled to biotin ligands were synthesized with a variety of PEG/PCL compositions. Block copolymeric nanoparticles harboring the anticancer drug paclitaxel were prepared via micelle formation in aqueous solution. The size of the biotin-conjugated PEG/PCL nanoparticles was determined by light scattering measurements to be 88-118 nm, depending on the molecular weight of the block copolymer, and remained less than 120 nm even after paclitaxel loading. From an in vitro release study, biotin-conjugated PEG/PCL nanoparticles containing paclitaxel evidenced sustained release profiles of the drug with no initial burst effect. The biotin-conjugated PEG/PCL block copolymer itself evidenced no significant adverse effects on cell viability at $0.005-1.0{\mu}g/mL$ of nanoparticle suspension regardless of cell type (normal human fibroblasts and HeLa cells). However, biotin-conjugated PEG/PCL harboring paclitaxel evidenced a much higher cytotoxicity for cancer cells than was observed in the PEG/PCL nanoparticles without the biotin group. These results showed that the biotin-conjugated nanoparticles could improve the selective delivery of paclitaxel into cancer cells via interactions with over-expressed biotin receptors on the surfaces of cancer cells.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.50-62
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• 1994

Opium, morphine and rotated natural and synthetic opiates have been used since antiquity, and to the present, for the relief of moderate and severe pain. Morphine and pharmacologically related drugs, however, produced an array of undesired or dangerous side effect that limit their use as analgesics. Prominent among the limiting side effects are constipation, respiratory depression, release of prolactin, and liability for the production of drug dependence. It was our aim to develop, if possible, a drug or class of drugs with analgesic activity similar to that of morphine, but without the serious side effects associated with morphine. Our overall strategy was to take advantage of advancing knowledge concerning multiple types of opioid receptors, to develop ligands selective for the delta type receptors, to determine whether delta receptor agonists offer advantages over mu agonists, then to design compounds with pharmacokinetic properties compatible with practical therapeutic application. All but the last of these objectives have been realized.

• Journal of Life Science
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• v.31 no.9
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• pp.849-855
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• 2021

Recently, as nanotechnology has been introduced and used in various fields, the development of new drugs has been accelerating. Nanoparticles have maintained blood drug concentration for extended periods of time with a single administration of the drug. The drug can then be selectively released only at the pathological site, thereby reducing side effects to other non-pathological sites. In addition, nanoparticles can be modified for selective target sites delivery for other specific diseases, with polymers being widely used in the manufacture of these nanoparticles. Poly (D,L-lactic-co-glycolic acid ) (PLGA) is one of the most extensively developed biodegradable polymers. PLGA is widely used in drug delivery for a variety of applications. It has also been approved by the FDA as a drug delivery system and is widely applied in controlled release formulations, such as in gene therapy treatments. PLGA nanoparticles have been developed as delivery systems with high efficiency to specific cell types by using passive and active targeting methods. After the development of a drug delivery system using PLGA nanoparticles, the drug is selectively delivered to the target site, and the effective blood concentration for extended periods of time is optimized according to the disease. In this review paper, we focus on ways to improve cell-specific treatment outcomes by examining the development of astrocyte selective nanoparticles based on PLGA nanomaterials for gene therapy.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.6
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• pp.753-761
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• 1998

Preconditioning of a heart with small doses of catecholamines induces a tolerance against the subsequent lethal ischemia. The present study was performed to find a specific receptor pathway involved with the catecholamine preconditioning and to test if adenosine plays a role in this cardioprotective effect. Isolated rat hearts, pretreated with small doses of ${\alpha}-\;or\;{\beta}-adrenergic$ agonists/antagonists, were subjected to 20 minutes ischemia and 20 minutes reperfusion by Langendorff perfusion method. Cardiac mechanical functions, lactate dehydrogenase and adenosine release from the hearts were measured before and after the drug treatments and ischemia. In another series of experiments, adenosine $A_1\;or\;A_2$ receptor blockers were treated prior to administration of adrenergic agonists. Pretreatments of a ${\beta}-agonist,\;isoproterenol(10^{-9}{\sim}10^{-7}\;M)$ markedly improved the post-ischemic mechanical function and reduced the lactate dehydrogenase release. Similar cardioprotective effect was observed with an ?-agonist, phenylephrine pretreatment, but much higher $concentration(10^{-4}\;M)$ was needed to achieve the same degree of cardioprotection. The cardioprotective effects of isoproterenol and phenylephrine pretreatments were blocked by a ${\beta}_1-adrenergic$ receptor antagonist, atenolol, but not by an ${\alpha}_1-antagonist,$ prazosin. Adenosine release from the heart was increased by isoproterenol, and the increase was also blocked by atenolol, but not by prazosin. A selective $A_1-adenosine$ receptor antagonist, 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX) blocked the cardioprotection by isoproterenol pretreatment. These results suggest that catecholamine pretreatment protects rat myocardium against ischemia and reperfusion injury by mediation of ${\beta}_1-adrenergic$ receptor pathway, and that adenosine is involved in this cardioprotective effect.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.1
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• pp.1-12
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• 1997

As it has been reported that the depolarization induced acetylcholine (ACh) release is modulated by activation of presynaptic $A_1$ adenosine heteroreceptor and various evidence suggest that indicate the $A_2$ adenosine receptor is present in the striatum, this study was undertaken to delineate the role of adenosine receptors on the striatal ACh release. Slices from the rat striatum were equilibrated with $[^3H]$choline and then the release amount of the labelled product, $[^3H]$ACh, which was evoked by electrical stimulation (rectangular pulses, 3 Hz, 2 ms, 24 mA, $5\;Vcm^{-1}$, 2 min), was measured, and the influence of various agents on the evoked tritium outflow was investigated. And also, quantitative receptor autoradiography and drug-receptor binding assay were performed in order to confirm the presence and characteristics of $A_1$ and $A_2$ adenosine receptors in the rat striatum. Adenosine $(10{sim}100\;{mu}M)$ and $N^6$-cyclopentyladenosine (CPA, $1{sim}100\;{mu}M)$ decreased the $[^3H]$ACh release in a dose-dependent manner without changing the basal rate of release in the rat striatum. The reducing effects of ACh release by adenosine and CPA were abolished by 8-cyclopentyl-1,3-dipropy-Ixanthine (DPCPX, 2 ${mu}M$), a selective $A_1$, adenosine receptor antagonist, treatment. The effect of adenosine was potentiated markedly by 3,7-dimethyl-1-propargylxanthine (DMPX, 10 ${mu}M$), a specific $A_2$ adenosine receptor antagonist. 2-P-(2-carboxyethyl)phenethylamimo-5'-N- ethylcarboxamidoadenosine hydrochloride (CGS-21680C), in concentrations ranging from 0.01 to 10 ${mu}M$, a recently introduced potent $A_2$ adenosine receptor agonist, increased the $[^3H]$ACh release in a dose related fashion without changing the basal rate of release. These effects were completely abolished by DMPX $(10\;{mu}M)$. In autoradiograrhy experiments, $[^3H]$2-chloro-$N^6$-cyclopentyladenosine ($[^3H]$ CCPA) bindings were highly localized in the hippocampus and the cerebral cortex. Additionally, lower levels of binding were found in the striatum. However, $[^3H]$CGS-21680C bindings were highly localized in the striatal region with the greatest density of binding found in the caudate nucleus and putamen. Lower levels of binding were also found in the nucleus accumbens and olfactory tubercle. In drug-receptor binding assay, binding of $[^3H]$ CCPA to $A_1$ adenosine receptors of rat striatal membranes was inhibited by CPA ($K_i$ = 1.6 nM) and N-ethylcarboxamidoadenosine (NECA, $K_i$ = 12.9 nM), but not by CGS-21680C ($K_i$ = 2609.2 nM) and DMPX ($K_i$ = 19,386 nM). In contrast, $[^3H]$CGS-21680C binding to $A_2$ denosine receptors was inhibited by CGS-21680C ($K_i$ = 47.6 nM) and NECA ($K_i$ = 44.9 nM), but not by CPA ($K_i$ = 2099.2 nM) and DPCPX ($K_i$ = 19,207 nM). The results presented here suggest that both types of $A_1$ and $A_2$ adenosine heteroreceptors exist and play an important role in ACh release in the rat striatal cholinergic neurons.