• Biomolecules & Therapeutics
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• v.18 no.4
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• pp.375-385
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• 2010

Conventional cancer chemotherapy is seriously limited by tumor cells exhibiting multidrug resistance (MDR), which is caused by changes in the levels or activity of membrane transporters that mediate energy-dependent drug efflux and of proteins that affect drug metabolism and/or drug action. Cancer scientists and oncologists have worked together for some time to understand anticancer drug resistance and develop pharmacological strategies to overcome such resistance. Much focus has been on the reversal of the MDR phenotype by inhibition of ATP-binding cassette (ABC) drug transporters. ABC transporters are a family of transporter proteins that mediate drug resistance and low drug bioavailability by pumping various drugs out of cells at the expense of ATP hydrolysis. Many inhibitors of MDR transporters have been identified, and though some are currently undergoing clinical trials, none are in clinical use. Herein, we briefly review the status of MDR in human cancer, explore the pathways of MDR in chemotherapy, and outline recent advances in the design and development of MDR modulators.

• Bulletin of the Korean Chemical Society
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• v.29 no.8
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• pp.1539-1544
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• 2008

A polymeric micelle, based on the poly(benzyl-L-histidine)-b-poly(ethylene glycol) (polyBz-His-b-PEG) diblock copolymer, was designed as a tumor-specific targeting carrier. The micelles (particle size: 67-80 nm, critical micelle concentration (CMC); 2-3 $\mu$g/mL) were formed from the diafilteration method at pH 7.4, as a result of self-assembly of the polyBz-His block at the core and PEG block on the shell. Removing benzyl (Bz) group from polyBz-His block provided pH-sensitivity of the micellar core; the micelles were physically destabilized in the pH range of pH 7.4-5.5, depending on the content of the His group free from Bz group. The ionization of His group at a slightly acidic pH promoted the deformation of the interior core. These pHdependent physical changes of the micelles provide the mechanism for pH-triggering anticancer drug (e.g., doxorubicin: DOX) release from the micelle in response to the tumor’s extracellular pH range (pH 7.2-6.5).

• 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.

• Archives of Pharmacal Research
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• v.10 no.1
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• pp.42-49
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• 1987

This study is to evaluate the potential use of aclarubicin-loaded gelatin microspheres as an intravascular biodegradable drug delivery system for the regional cancer therapy. The diameter of the microspheres prepared by water in oil emulsion polymerization could be controlled by adjusting the stirring rate in the range of 10-50 $\mu$m : D(in $\mu$m) = -73.8 log (rpm) + 262.7. The addition of proteolytic enzyme increased the in vitro aclarubicin release but it did not change the amount of the initial burst release which reached about 45%. Microspheres injected intravenously into the mouse tail vein embolized only to the lung when observed by fluorescence microscopy. From histological examination following injection of gelatin microspheres into mouse femoral muscle, mild inflammation was observed from the appearance of neutrophils after 2 days and rapid repair process was confirmed thereafter. Biodegradation process of gelatin microspheres lodged on the pulmonary capillary bed was followed up by microscopic observation; degradation was taking place by about 36 hrs, followed by severe damage on the spheerical shape and microspheres was no longer found 10 days after injection.

• Biomolecules & Therapeutics
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• v.21 no.2
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• pp.89-96
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• 2013

Atherosclerotic vascular dysfunction is a chronic inflammatory process that spreads from the fatty streak and foam cells through lesion progression. Therefore, its early diagnosis and prevention is unfeasible. Reactive oxygen species (ROS) play important roles in the pathogenesis of atherosclerotic vascular disease. Intracellular redox status is tightly regulated by oxidant and antioxidant systems. Imbalance in these systems causes oxidative or reductive stress which triggers cellular damage or aberrant signaling, and leads to dysregulation. Paradoxically, large clinical trials have shown that non-specific ROS scavenging by antioxidant vitamins is ineffective or sometimes harmful. ROS production can be locally regulated by cellular antioxidant enzymes, such as superoxide dismutases, catalase, glutathione peroxidases and peroxiredoxins. Therapeutic approach targeting these antioxidant enzymes might prove beneficial for prevention of ROS-related atherosclerotic vascular disease. Conversely, the development of specific antioxidant enzyme-mimetics could contribute to the clinical effectiveness.

• Interdisciplinary Bio Central
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• v.2 no.4
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• pp.9.1-9.5
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• 2010

Many neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, are devastating disorders that affect millions of people worldwide. However, the number of therapeutic options remains severely limited with only symptomatic management therapies available. With the better understanding of the pathogenesis of neurodegenerative diseases, discovery efforts for disease-modifying drugs have increased dramatically in recent years. However, the process of translating basic science discovery into novel therapies is still lagging behind for various reasons. The task of finding new effective drugs targeting central nervous system (CNS) has unique challenges due to blood-brain barrier (BBB). Furthermore, the relatively slow progress of neurodegenerative disorders create another level of difficulty, as clinical trials must be carried out for an extended period of time. This review is intended to provide molecular and cell biologists with working knowledge and resources on CNS drug discovery and development.

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.178.1-178.1
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• 2000

• Nuclear Medicine and Molecular Imaging
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• v.42 no.5
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• pp.337-346
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• 2008

Applications of nanotechnology in the medical field have provided the fundamentals of tremendous improvement in precise diagnosis and customized therapy. Recent advances in nanomedicine have led to establish a new concept of theragnosis, which utilizes nanomedicines as a therapeutic and diagnostic tool at the same time. The development of high affinity nanoparticles with large surface area and functional groups multiplies diagnostic and therapeutic capacities. Considering the specific conditions related to the disease of individual patient, customized therapy requires the identification of disease target at the cellular and molecular level for reducing side effects and enhancing therapeutic efficiency. Well-designed nanoparticles can minimize unnecessary exposure of cytotoxic drugs and maximize targeted localization of administrated drugs. This review will focus on major pharmaceutical nanomaterials and nanoparticles as key components of designing and surface engineering for targeted theragnostic drug development.

• Journal of Integrative Natural Science
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• v.5 no.1
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• pp.22-26
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• 2012

Chemokine receptor antagonists have potential applications in field of drug discovery. Although the chemokine receptors are G-protein-coupled receptors, their cognate ligands are small proteins (8 to 12 kDa), and so inhibiting the ligand/receptor interaction has been challenging. In particular, CCR2 and CCR5 and their ligands have been implicated in the pathophysiology of a number of diseases, including rheumatoid arthritis and multiple sclerosis. Based on their roles in disease, they have been attractive targets for the pharmaceutical industry, targeting both CCR2 and CCR5 could be a useful strategy. Because of the importance of these receptors, providing information regarding the binding site is of prime importance. Herein, we report the comparison of CCR2 of CCR5 binding sites both sequentially as well as structurally. We also urged the importance of crucial residues in the binding site, to facilitate the development of dual antagonists targeting both the receptors. These results could also be useful for the design of novel and potent dual CCR2 and CCR5 antagonists using structure based drug design.

• Biomedical Science Letters
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• v.27 no.1
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• pp.1-11
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• 2021

Cancer stem cells, which are known to drive tumor formation and maintenance, are a major obstacle in the effective treatment of various types of cancer. Trans-membrane glycoprotein mucin 1 antigen and cell surface glycogen CD44 antigen are well-known surface markers of breast cancer cells and breast cancer stem cells, respectively. To effectively treat cancer cells and cancer stem cells, we developed a new drug-encapsulating liposome conjugated with dual-DNA aptamers specific to the surface markers of breast cancer cells and their cancer stem cells. These two aptamer (Apt)-targeted liposomes, which were prepared to encapsulate doxorubicin (Dox), were named "Dual-Apt-Dox". Dual-Apt-Dox is significantly more cytotoxic to both cancer stem cells and cancer cells compared to liposomes lacking the aptamers. Furthermore, we demonstrated the inhibitory efficacy of Dual-Apt-Dox against the experimental lung metastasis of breast cancer stem cells and cancer cells in athymic nude mice. We also showed the potent antitumor effects of dual-aptamer-conjugated liposome systems by targeting cancer cells as well as cancer stem cells. Thus, our data indicate that dual-aptamer-conjugated liposome systems can prove to be effective drug delivery vehicles for breast cancer therapy.