• Title/Summary/Keyword: targeting efficiency

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Hepatic Uptake and Stability of Acyclovir-Asialofetuin Conjugate (아시클로버-아시알로페투인 접합체의 간 포획 및 안정성)

  • Son, Sung-Ho;Huh, Keun;Lee, Young-Dae;Oh, Doo-Man;Yong, Chul-Soon
    • Journal of Pharmaceutical Investigation
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    • v.27 no.1
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    • pp.1-10
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    • 1997
  • For the purpose of improving the chemotherapeutic index of acyclovir(ACV), it was conjugated with asialofetuin(AF), which has been reported to enter into hepatocytes. When $[H^3]$ acyclovir in itself or its conjugate were administered to rats, the latter was taken up more selectively by the liver than any other tissues. The stability of ACVMP-AF conjugate in phosphate buffer (pH 5.0) and rat liver homogenate showed a pseudo-first order profile. ACVMP-AF, however, was relatively stable in pH7.4 phosphate buffer and rat plasma. The conjugate was added to the isolated rat hepatocyte and cellular uptake was monitored by scintillation counting for up to 6 hours at $37^{\circ}C$. Hepatocytes incubated with the conjugate exhibited radioactivities significantly enhanced over control levels dose-dependently, i.e., a 3-40 fold increase in radioactivities was observed over controls at the conjugate concentrations of $0.1-10\;{\mu}g/ml$. The AUQ in the liver, kidney, spleen, intestine and lung was higher in treatment with ACVMP-AF than that in treatment with ACV. In treatment with ACVMP-AF, the weighted-average overall drug targeting efficiency(Te) for the liver was higher than in treatment with ACV(57.00 vs 13.31 %), and the weighted-average tissue exposure(Re) was 5.03 for the liver. These results indicated that ACVMP-AF conjugate was rapidly taken up by hepatocytes and could be an efficient and selective hepatic targeting system.

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Improved Antitumor Efficacy of Hyaluronic Acid-Complexed Paclitaxel Nanoemulsions in Treating Non-Small Cell Lung Cancer

  • Kim, Joo-Eun;Park, Young-Joon
    • Biomolecules & Therapeutics
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    • v.25 no.4
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    • pp.411-416
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    • 2017
  • Paclitaxel (PTX) is a effectively chemotherapeutic agent which is extensively able to treat the non-small cell lung, pancreatic, breast and other cancers. But it is a practically insoluble drug with water solubility less than $1{\mu}g/mL$, which restricts its therapeutic application. To overcome the problem, hyaluronic acid-complexed paclitaxel nanoemulsions (HPNs) were prepared by ionic complexation of paclitaxel (PTX) nanoemulsions and hyaluronic acid (HA) to specifically target non-small cell lung cancer. HPNs were composed of ${\small{DL}}-{\alpha}$-tocopheryl acetate, soybean oil, polysorbate 80, ferric chloride, and HA and fabricated by high-pressure homogenization. The HPNs were $85.2{\pm}7.55nm$ in diameter and had a zeta potential of $-35.7{\pm}0.25mV$. The encapsulation efficiency was almost 100%, and the PTX content was 3.0 mg/mL. We assessed the in vivo antitumor efficacy of the HPNs by measuring changes in tumor volume and body weight in nude mice transplanted with CD44-overexpressing NCI-H460 xenografts and treated with a bolus dose of saline, $Taxol^{(R)}$, PTX nanoemulsions (PNs), or HPNs at a dose of 25 mg/kg. Suppression of cancer cell growth was higher in the PN- and HPN-treated groups than in the $Taxol^{(R)}$ group. In particular, HPN treatment dramatically inhibited tumor growth, likely because of the specific tumor-targeting affinity of HA for CD44-overexpressed cancer cells. The loss of body weight and organ weight did not vary significantly between the groups. It is suggest that HPNs should be used to effective nanocarrier system for targeting delivery of non-small cell lung cancer overexpressing CD44 and high solubilization of poorly soluble drug.

Synthesis of N-Stearyl lactobionamide(N-SLBA) and Preparation of Neo-galactosylated Liposome (N-스테아릴락토비온아미드의 합성과 이를 이용한 리포좀의 제조)

  • Kim, Chong-Kook;Min, Mi-Hong;Min, Kyoung-Hee;Lah, Woon-Ryong;Lee, Bong-Jin;Kim, Yang-Bae
    • YAKHAK HOEJI
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    • v.36 no.2
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    • pp.159-166
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    • 1992
  • A neoglycolipid, N-stearyl lactobionamide(N-SLBA) was synthesized and the incorporation of the neoglycolipid into liposomes was achieved in order to prepare neo-galactosylated liposome as potential drug carrier for active targeting to galactose receptor existing cell and tissue. N-SLBA was synthesized by the covalent linkage between carboxyl group of lactobionic acid and amino group of stearylamine(SA). The yield of N-SLBA was about 52.3%. It was identified with $1650\;cm^{-1}$ in IR chart, 7.5 ppm in NMR spectra, $61^{\circ}C$ endothermic peak in DSC heating curve. Surface-modified large unilamellar vesicle with galactose(N-SLBA-LUV) could be prepared with N-SLBA by reverse evaporation method. N-SLBA-LUV was identified by TEM and measuring of membrane function. The maximum amount of N-SLBA incorporated into liposome is up to about 15 mol%. Compared with control liposome (SA-LUV), N-SLBA-LUV showed lower encapsulation efficiency of MTX. It might due to the loss of positive surface charge of stearylamine. N-SLBA-LUV was similar to SA-LUV in aspect of osmotic behavior. N-SLBA-LUV prepared with N-SLBA would be expected to be a good carrier for active targeting to galactose receptor existing cell and tissue.

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Synthesis of a PEGylated tracer for radioiodination and evaluation of potential in tumor targeting

  • Abhinav Bhise;Sushil K Dwivedi;Kiwoong Lee;Jeong Eun Lim;Subramani Rajkumar;Woonghee Lee;Seong Hwan Cho;Jeongsoo Yoo
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.7 no.2
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    • pp.79-84
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    • 2021
  • Radiopharmaceuticals are important for tumor diagnosis and therapy. To deliver a radiotracer at the desired target excluding non-targeted tissues is difficult The development of a targeted tracer that has a good clearance profile while maintaining high biostability and biocompatibility is key to optimizing its biodistribution and transport across biological barriers. Improving the hydrophilicity of radiotracers by PEGylation can reduce serum binding, allowing the tracer to circulate without retention and reducing its affinity for non-targeted tissues. In this study, we synthesized a new benzamido tracer (SnBz-PEG36) with the introduction of a low molecular weight polyethylene glycol unit (PEG36, ~2,100 Da). The tumor targeting efficiency and biodistribution of [131I]-Bz-PEG36 or radiotracer-loaded liposomes were evaluated after their administration to normal mice or mouse tumor models including CT26 (xenograft) and 4T1 (xenograft and orthotopic). Most of the radiotracer was cleared out rapidly (1-24 h post-administration) through the kidney and there was little tumor uptake.

Transgenesis and Germ Cell Engineering in Domestic Animals

  • Lee, C.K.;Piedrahita, J.A.
    • Asian-Australasian Journal of Animal Sciences
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    • v.16 no.6
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    • pp.910-927
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    • 2003
  • Transgenesis is a very powerful tool not only to help understanding the basics of life science but also to improve the efficiency of animal production. Since the first transgenic mouse was born in 1980, rapid development and wide application of this technique have been made in laboratory animals as well as in domestic animals. Although pronuclear injection is the most widely used method and nuclear transfer using somatic cells broadens the choice of making transgenic domestic animals, the demand for precise manipulation of the genome leads to the utilization of gene targeting. To make this technique possible, a pluripotent embryonic cell line such as embryonic stem (ES) cell is required to carry genetic mutation to further generations. However, ES cell, well established in mice, is not available in domestic animals even though many attempt to establish the cell line. An alternate source of pluripotent cells is embryonic germ (EG) cells derived from primordial germ cells (PGCs). To make gene targeting feasible in this cell line, a better culture system would help to minimize the unnecessary loss of cells in vitro. In this review, general methods to produce transgenic domestic animals will be mentioned. Also, it will focus on germ cell engineering and methods to improve the establishment of pluripotent embryonic cell lines in domestic animals.

A Study on Space Planning of High School Considering the Management Realities of Education Curricula (교육과정 운영실태를 고려한 고등학교의 공간계획에 관한 연구 - 방과후 활용을 중심으로 -)

  • Lee, Jae Lim
    • The Journal of Sustainable Design and Educational Environment Research
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    • v.3 no.2
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    • pp.51-74
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    • 2003
  • This study has presented construction planning data or material. which can maximize the efficiency of school facilities; in other words, to utilize school facilities as local continuing education facilities in terms of use rate, as well as to make school facilities to accommodate the 7th education curricula. This study has been carried out through questionnaire survey on currently executed various curricular operation types, targeting people in charge of drawing up and operation of the curricula in liberalarts high school. The questionnaire survey has also been conducted on ideal teaching-learning type by subject, targeting teachers in charge of individual subject. The expansion of specialized curricula rooms and classrooms, as well as classrooms by level and ICT-related rooms, are required to invigorate continuing education, which utilizes smooth operation of the 7th education curricula and school facilities. I also assume that implementation of school curricula and the role as local continuing education facilities can be fulfilled, through activated deployment type and operation programs with which management of the facilities becomes easy, in order to utilize those classrooms to be used for continuing education.

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Nanomedicine: Drug Delivery Systems and Nanoparticle Targeting (나노의학: 나노물질을 이용한 약물전달시스템과 나노입자의 표적화)

  • Youn, Hye-Won;Kang, Keon-Wook;Chung, June-Key;Lee, Dong-Soo
    • 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.

Detection of Mycobacterium leprae by Real-time PCR Targeting Mycobacterium leprae-Specific Repetitive Element Sequence

  • Jin, Hyun-Woo;Wang, Hye-Young;Kim, Jong-Pill;Cho, Sang-Nae;Lee, Hye-Young
    • Biomedical Science Letters
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    • v.16 no.2
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    • pp.127-131
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    • 2010
  • Mycobacterium leprae detection is difficult even with molecular biological techniques due to the low sensitivity of current methodologies. In this report, real-time PCR targeting the M. leprae-specific repetitive element (RLEP) sequence was developed as a new diagnostic tool and evaluated using clinical specimens. For this, M. leprae DNAs were extracted from skin biopsy specimens from 80 patients and analyzed by real-time PCR using TaqMan probe. Then, the detection efficiency of the real-time PCR was compared with that of standard PCR. In brief, the rate of positive detection by the standard PCR and real-time PCR was 32.50% and 66.25%, respectively. The results seemed to clearly show that the TaqMan real-time PCR developed in this study may be a useful tool for sensitive detection of M. leprae from clinical specimens.

Observation of Gene Edition by the Transient Expression of CRISPR-Cas9 System During the Development of Tomato Cotyledon (Agrobacterium을 이용한 토마토 떡잎에서 CRISPR-Cas9 시스템의 임시발현 시 토마토 떡잎 발달 단계에 따른 유전자교정 효율 변화)

  • Kim, Euyeon;Yang, So Hee;Park, Hyosun;Koo, Yeonjong
    • Korean Journal of Environmental Agriculture
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    • v.40 no.3
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    • pp.186-193
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    • 2021
  • BACKGROUND: Before generating transgenic plant using the CRISPR-Cas9 system, the efficiency test of sgRNAs is recommended to reduce the time and effort for plant transformation and regeneration process. The efficiency of the sgRNA can be measured through the transient expression of sgRNA and Cas9 gene in tomato cotyledon; however, we found that the calculated efficiency showed a large variation. It is necessary to increase the precision of the experiment to obtain reliable sgRNA efficiency data from transient expression. METHODS AND RESULTS: The cotyledon of 11th, 15th, 19th, and 23rd-day-old tomato (Solanum lycopersicum cv. Micro-Tom) were used for expressing CRISPR-Cas9 transiently. The agrobacterium harboring sgRNA for targeting ALS2 gene of tomato was injected through the stomata of leaf adaxial side and the genomic DNA was extracted in 5 days after injection. The target gene edition was identified by amplifying DNA fragment of target region and analyzing with Illumina sequencing method. The target gene editing efficiency was calculated by counting base deletion and insertion events from total target sequence read. CONCLUSION: The CRISPR-Cas9 editing efficiency varied with tomato cotyledon age. The highest efficiency was observed at the 19-day-old cotyledons. Both the median and mean were the highest at this stage and the sample variability was also minimized. We found that the transgene of CRISPR-Cas9 system was strongly correlated with plant leaf development and suggested the optimum cotyledon leaf age for Agrobacterium-mediated transfection in tomato.

Redesigning nozzle propeller of trawl vessel for improving towing speed (트롤어선의 예망속도 향상을 위한 추진기 구조개선)

  • Hong, Jin-Keun;Kang, Il-Kwon;Kim, Hyung-Seok;Jeong, Seong-Jae
    • Journal of the Korean Society of Fisheries and Ocean Technology
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    • v.46 no.4
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    • pp.476-486
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    • 2010
  • Fishing efficiency of a trawl vessel can be enhanced by increasing the swept area per unit time, which can be attained either by increasing the mouth size of the net, or by increasing the towing speed. To improve fishing and fuel efficiency of trawl vessels targeting fishes of greater mobility, in which the towing speed is more critical in determining fishing efficiency, we conducted a series of model tests to evaluate the performance of the newly-designed nozzle propeller before installing it in a trawl vessel to verify its towing speed and fuel efficiency in the sea. By conducting further model tests in the experimental basin, we redesigned the propeller of stern trawler to improve the resistance and propulsion performance. Through actual fishing operations, we evaluated the improvement in fuel and fishing efficiency by installing the new nozzle propeller. The trawling speed increased by 0.6kts at the same engine power (RPM), while the engine margin increased by more than 20%. The increased towing speed by installing the redesigned propeller is expected to enhance fishing performance through increasing the number of hauling- and casting operations per unit times, while shortening the towing duration. Analysis of the Catch-Per-Unit-Effort (CPUE) data indicated that the mean CPUE of trawl fishery increased from 3.04kg/m in year 2007 to 6.15kg/m in year 2008, confirming enhanced fishing efficiency by adopting the redesigned propeller.