• Archives of Pharmacal Research
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• 제29권7호
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• pp.598-604
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• 2006

In many conventional drug delivery systems in vogue, failure to deliver efficient drug delivery at the target site/organs; is evident as a result, less efficacious pharmacological response is elicited. Microspheres can be derived a remedial measure which can improve site-specific drug delivery to a considerable extent. As an application, Lung-targeting Ofloxacin-loaded gelatin microspheres (GLOME) were prepared by water in oil emulsion method. The Central Composite Design (CCD) was used to optimize the process of preparation, the appearance and size distribution were examined by scanning electron microscopy, the aspects such as in vitro release characteristics, stability, drug loading, loading efficiency, pharmacokinetics and tissue distribution in albino mice were studied. The experimental results showed that the microspheres in the range of $0.32-22\;{\mu}m$. The drug loading and loading efficiency were 61.05 and 91.55% respectively. The in vitro release profile of the microspheres matched the korsmeyer’s peppas release pattern, and release at 1h was 42%, while for the original drug, ofloxacin under the same conditions 90.02% released in the first half an hour. After i.v. administration (15 min), the drug concentration of microspheres group in lung in albino mice was $1048\;{\mu}g/g$, while that of controlled group was $6.77\;{\mu}g/g$. GLOME found to release the drug to a maximum extent in the target tissue, lungs.

• 대한의생명과학회지
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• 제22권4호
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• pp.215-219
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• 2016

The problems of tuberculosis and its drug resistance are very severe. Therefore, rapid and accurate drug susceptibility assay is required. Recently, there has been an increased understanding of the genetic mechanism of Mycobacterium tuberculosis (MTB) drug resistance as well as advancement of molecular technologies. While many gene mutations correlate well with drug resistance, many genes do not show a strong correlation with drug resistance. For this reason, the current study assessed the utility of rpoB mRNA as a target to detect live mycobacteria. In this study, RT-PCR targeting of rpoB mRNA in BCG treated with rifampin was performed. Conventional RT-PCR and real-time PCR targeting rpoB mRNA as well as 85B mRNA was performed to determine whether these two methods could distinguish between viable and non-viable MTB. The levels of rpoB and 85B mRNA detected by RT- PCR were compared in parallel with colony forming unit counts of BCG that were treated with rifampin for different periods of time. The data suggests that that even though both mRNA levels of rpoB and 85B decreased gradually when rifampin-treatment increased, the rpoB mRNA seemed to represent live bacteria better than 85B mRNA. This study clearly indicates that RT-PCR is a good method to monitor viable cell counts in the liquid culture treated with the anti-tuberculosis drug.

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of the Pharmaceutical Society of Korea
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• pp.236.1-236.1
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• 2001

• Journal of Pharmaceutical Investigation
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• 제40권4호
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• pp.201-212
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• 2010

Self-organized nanogels from polysaccharide derivatives offer a promising approach in treatment of cancer due to their flexibility in chemistry and their ability to improve the therapeutic index of a drug by modifying biodistribution by their preferential localization at target sites and lower distribution in normal healthy tissues. These properties have promoted studies of active cancer targeting by self-organized nanogels for even better accumulation in solid tumors. However although many researchers have reported their potential by using cell culture systems and small animal tumor models in cancer therapy, these nanogels need more decoration such as conjugation with targeting moiety and endowment of stimuli-sensitivity for precise targeting of the cancer site. In this review, we summarize the recent efforts in developing novel targeting approaches via active endocytosis and stimuli-sensitive systems responding to hyperthermic or acidic tumor pH conditions.

• Journal of Pharmaceutical Investigation
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• 제24권4호
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• pp.217-225
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• 1994

With the purpose of improving the therapeutic index of $[^3H]$ acyclovir (ACV) in the treatment of chronic hepatitis B infection, asialofetuin (AF) which after selective interaction with Ashwell's receptor specifically enters into hepatocytes, was chosen as a carrier system for hepatic targeting. This drug was first converted to its monophosphate (ACVMP), which was subsequently activated by water soluble carbodiimide to conjugate with ${\varepsilon}-NH_2$ groups of Iysine residues of AF. The molar ratio of ACVMP to AF in the conjugate was 3.9. In rats, elimination of ACVMP-AF conjugate after i.v. injection showed two phase elimination kinetics. Initial apparent elimination rate constant in rats was $0.191\;min^{-1}$ which was greater than that of ACV. The elimination rate constant from terminal phase was $0.021\;min^{-1}$. Area under the total radioactivities versus time curve was found to be several times larger in liver than in other organs (spleen, intestine, lung and kidney) after i.v. administration of the conjugate labelled in the drug moiety. The above results suggested that ACVMP-AF conjugate was rapidly taken up by hepatocytes and could be a useful hepatic targeting system.

• Bulletin of the Korean Chemical Society
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• 제29권4호
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• pp.887-890
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• 2008

• 대한약침학회지
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• 제19권1호
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• pp.7-15
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• 2016

Objectives: Malaria has been a major global health problem in recent times with increasing mortality. Current treatment methods include parasiticidal drugs and vaccinations. However, resistance among malarial parasites to the existing drugs has emerged as a significant area of concern in anti-malarial drug design. Researchers are now desperately looking for new targets to develop anti-malarials drug which is more target specific. Malarial parasites harbor a plastid-like organelle known as the 'apicoplast', which is thought to provide an exciting new outlook for the development of drugs to be used against the parasite. This review elaborates on the current state of development of novel compounds targeted againstemerging malaria parasites. Methods: The apicoplast, originates by an endosymbiotic process, contains a range of metabolic pathways and housekeeping processes that differ from the host body and thereby presents ideal strategies for anti-malarial drug therapy. Drugs are designed by targeting the unique mechanism of the apicoplasts genetic machinery. Several anabolic and catabolic processes, like fatty acid, isopenetyl diphosphate and heme synthess in this organelle, have also been targeted by drugs. Results: Apicoplasts offer exciting opportunities for the development of malarial treatment specific drugs have been found to act by disrupting this organelle's function, which wouldimpede the survival of the parasite. Conclusion: Recent advanced drugs, their modes of action, and their advantages in the treatment of malaria by using apicoplasts as a target are discussed in this review which thought to be very useful in desigining anti-malarial drugs. Targetting the genetic machinery of apicoplast shows a great advantange regarding anti-malarial drug design. Critical knowledge of these new drugs would give a healthier understanding for deciphering the mechanism of action of anti-malarial drugs when targeting apicoplasts to overcome drug resistance.

• Biomolecules & Therapeutics
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• 제10권1호
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• pp.37-42
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• 2002

Brain drug targeting through the blood-brain barrier (BBB) in vivo is possible with peptidornirnetic monoclonal antibodies that undergo receptor-mediated transcytosis through the BBB. Monoclonal antibody to the rat transferrin receptor, such as the OX26 was studied in rats as a transport vector through BBB on the transferrin receptor. But, OX26 is not an effective brain delivery vector in mouse. In the present studies, rat monoclonal antibody, 8D3 to the mouse transferrin receptor were evaluated for brain drug targeting vector intransgenic mouse model. Pharrnacokinetic parameters in plasma and organ uptakes were determined at varioustimes after i.v. bolus injection of [$^{}125}I$] 8D3 in Balb/c mice. Brain uptake of [$^{}125}I$] 8D3 was also studied with an internal carotid artery perfusioncapillary depletion method. After i.v. injection of [$^{}125}I$] 8D3, plasma concentrations declined biexponentially with elimination half lift of approximately 2.2 hours. Brain uptake of [$^{}125}I$] 8D3 was $0.50{\pm}0.09$ persent of injected dose per g brain after 2 hours i.v. injection. After perfusion 5 min the apparent volume of distibution of [$^{}125}I$] 8D3 in brain was $22.3 {\mu}l/g,$ which was 4.8 fold higher than the intravascular volume. These studies indicate rat monoclonal antibody to the mouse transferrin receptor, 8D3 may be used for brain drug targeting vector in mice.

• Journal of Pharmaceutical Investigation
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• 제22권1호
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• pp.1-10
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• 1992

The use of erythrocyte as drug carrier has been reviewed, Carrier erythrocytes have proven to offer many advantages for delivery of therapeutic agents, especially in the treatment of inherited enzyme deficiency and cancer. Carrier erythrocytes are biodegradable and nonimmunogenic. Encapsulated drugs may be protected from premature degradation, inactivation and excretion. Carrier erythrocytes may be used as a slow-release system. Targeting of encapsulated drugs directly to a site of action is another possibility. Methods for encapsulating drugs into erythrocytes, the fate of carrier erythrocytes in vivo, the strategies of targeting carrier erythrocytes to special organs and in vivo applications of erythrocytes have been discussed. The encapsulation of drugs in erythrocytes has shown attractive possibilites in future use.

• Macromolecular Research
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• 제14권3호
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• pp.387-393
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• 2006

Nanoparticles of Poly(L-glutamic acid) (PG) conjugated to the anticancer drug paclitaxel and targeted moiety folic acid (FA) were synthesized and characterized in vitro. The nanoparticles were designed to take advantage of FA targeting to folate receptor (FR) positive cancer cells. The chemical composition of the conjugate was characterized by $^1H-NMR$, FTIR and UV/vis spectroscopy. The selective cytotoxicity of the FA-PG-paclitaxel conjugates was evaluated in FR positive cancer cells. The interaction of the conjugate was visualized by fluorescence microscopy with results confirming the successful preparation of the conjugate and the production of nanoparticles of about 200-300 nm in diameter. The amount of paclitaxel conjugated to FA-PG was 25% by weight. Cellular uptake of the conjugate was FA dependent, and the conjugate uptake was mediated specifically by the folate receptor. These results demonstrate the improved selective toxicity and effective delivery of an anticancer drug into FR bearing cells in vitro.