• 제목/요약/키워드: Biodistribution

검색결과 143건 처리시간 0.024초

Biodistribution and Genotoxicity of Transferrin-Conjugated Liposomes/DNA Complexes in Mice

  • Lee Sang Mi;Kim Jin-Seok;Oh Yu-Kyoung;Lee Yong-Bok;Sah Hongkee
    • Macromolecular Research
    • /
    • 제13권3호
    • /
    • pp.218-222
    • /
    • 2005
  • Transferrin-conjugated liposomes ($T_f$-liposomes) were made and formulated with pCMVluc DNA to form a lipoplex. Among the various formulations studied, the $T_f$-liposome: pCMVluc DNA complex at a ratio of 5: 1 (wt/wt) showed the highest transfection efficiency, which was twice that of $Lipofectin^{TM}$ on HeLa cells. The maxi-mum tolerated dose (MTD) of this lipoplex formulation from a single intravenous injection was over 10 mg/kg in healthy ICR mice. The RT-PCR results showed that the highest level of luciferase mRNA was detected in the lungs, followed by the liver, spleen, heart and kidneys, after an intravenous injection into mice. Two weeks after the injection, the levels of luciferase mRNA decreased gradually in the liver, spleen, heart, and kidney, but not in the lungs. The micro-array study showed that the cancer-related genes, including the bcl 6 gene, were highly up-regulated by the treatment with $T_f$-liposome/ pCMVluc DNA complex on HeLa cells, indicating that there were possible interactions between the host chromosomal DNA and the $T_f$-liposome within the cells. The results obtained from this study are expected to be useful for designing a safe and efficient gene delivery system using transferrin-conjugated liposomes.

Lactosaminated N-Succinyl-chitosan: Preparation and Biodistribution into the Intestine, Bone, Lymph Nodes and Male Genital Organs after I.v. Administration

  • Kato, Yoshinori;Onishi, Hiraku;Machida, Yoshiharu
    • Macromolecular Research
    • /
    • 제11권5호
    • /
    • pp.382-386
    • /
    • 2003
  • Reductive amination of N-succinyl-chitosan (1) and lactose using sodium cyanoborohydride in 1/15 M phosphate buffer (pH 6.0) for 6 d was suitable for the preparation of lactosaminated N-succinyl-chitosan (2). At 8, 24 and 48 h after i.v. administration of fluorescently labeled 1 (1') or 2 (2'), Peyer's patch, mesenteric lymph nodes, testes, prostate, preputial grand, intestine (small intestine plus cecum), femoral muscle, backbone and peritoneum were taken. Peyer's patch and mesenteric lymph nodes were put together as lymph nodes. Over 10% of dose/g tissue was distributed to the prostate and lymph nodes at 48 h post-administration in both l' and 2'.2' was easily distributed into not only the liver but also prostate, intestine, preputial gland and lymph nodes. Although galactose receptors are known to exist not only on the liver parenchymal cells but also on prostate and testes, the selective distribution of 2' into the prostate and the testes were not observed clearly. This study suggested that 1 and 2 should have possibilities for both the prevention and cure of lymph node metastasis as drug carriers.

I-123 표지 지방산의 체내 분포 및 대사(I) : [I-123]15-(p-iodophenyl)pentadecanoic acid(IPPA) (Biodistribution and Metabolism of I-123 Labelled Fatty Acid(I) : [I-123]15-(p-iodophenyl)pentadecanoic acid(IPPA))

  • 장영수;이동수;정재민;서용섭;정준기;이명철;고창순
    • 대한핵의학회지
    • /
    • 제32권1호
    • /
    • pp.50-60
    • /
    • 1998
  • 국내에서 제조한 I-123-IPPA의 안정성 및 동물체내 분포와 대사, 그리고 SPECT 영상 분석 방법을 연구하였다. I-123-IPPA의 안정성을 보기 위하여 사람 및 랫트와 마우스 혈청과 반응시킨 후 1 시간 동안 관찰한 결과 I-123이 유리되지 않았다. 마우스에 I-123-IPPA 투여 후 장기를 적출 하여 본 체내 분포는 심장의 단위무게당 섭취는 5분에 14.5%ID/g 기관당 섭취는 1.9%ID/organ 이었다. 주사량 대비 심장 섭취율은 주사 60분에 처음의 1/4-1/6로 줄었다. 심근대 혈액 비와 심근 대 폐와 심근 대 간 섭취 비는 I-123-IPPA 투여 후 처음 5분까지 증가하다가 이후 계속 감소하였다. 랫트에 I-123-IPPA를 투여한 후 혈액과 소변 크로마토그라피에는 I-123-IPPA가 15-20분 후에 혈액이나 소변 중에 I-123-IPPA는 거의 남지 않고 여러 중간 물질이 되었다. 심근경색 실험견에 경색을 만들기 전과 후에 시행한 심근 동적 SPECT에서 정상 심근은 I-123-IPPA가 섭취되었다가 제거되는 모습으로, 경색 부위는 I-123-IPPA의 섭취 결손으로 보였다. 심근의 I-123-IPPA SPECT에 보이는 결손은 Tc-99m-MIBI SPECT와 F-18-FDG PET에 보이는 결손과 비슷하였다. 이상의 결과는 원자력병원 싸이클로트론 응용 연구실에서 제조한 I-123-IPPA가 심근 질환의 대사를 평가하는데 사용할 수 있음을 나타낸다.

  • PDF

L-3-[$^{123}I$iodo-${\alpha}$-methyltyrosine 합성과 9L Glioma 이식 백서 분포조사 (Synthesis of L-3-[$^{123}I$]iodo-${\alpha}$-methyltyrosine and Biodistribution in 9L Glioma Bearing Rats)

  • 양승대;임상무;우광선;정위섭;전권수;서용섭;임종석;박현;윤용기;이종두
    • 대한핵의학회지
    • /
    • 제29권1호
    • /
    • pp.105-109
    • /
    • 1995
  • Tyrosine의 유도체인 [$^{123}I$]IMT를 각종 악성종양의 SPECT에 이용하기 위하여 표지시 반응조건과 뇌종양이식 백서에서의 체내 동태를 연구하여 다음과 같은 결과를 얻었다. AMT의 [$^{123}I$] 표지에 chloramine-T 보다 Iodobead를 이용하는 것이 훨씬 간편하고 수율이 높았으며, Iodobead 1개, AMT $200{\mu}g/100{\mu}L$ phosphate buffer, PH 5.5, 상온에서 7분간 반응시키는 것이 최적 반응조건이었다. 9L glioma 이식 백서 체내동태는 [$^{123}I$]IMT가 신장으로 배설됨과 체내에서 탈요오드 반응이 일어남이 추측되었고, 정상조직의 3배 방사능 섭취가 관찰되어, 각종 뇌종양의 진단 및 치료 후 경과 관찰에 이용 가능성이 보여 임상연구의 진행이 기대된다.

  • PDF

분자영상 방사성추적자의 생산에 사용되는 방사성동위 원소 표지방법 (Radiolabeling Methods Used for Preparation of Molecular Probes)

  • 최연성
    • 대한핵의학회지
    • /
    • 제38권2호
    • /
    • pp.121-130
    • /
    • 2004
  • Molecular imaging visualizes cellular processes at a molecular or genetic level in living subjects, and diverse molecular probes are used for this purpose. Radiolabeling methods as well as radioisotopes are very important in preparation of molecular probes, because they can affect the biodistribution in tissues and the excretion route. In this review, the molecular probes are divided into small organic molecules and macromolecules such as peptides and proteins, and their commonly used radiolabeling methods are described.

Formulation and Characterization of Antigen-loaded PLGA Nanoparticles for Efficient Cross-priming of the Antigen

  • Lee, Young-Ran;Lee, Young-Hee;Im, Sun-A;Kim, Kyung-Jae;Lee, Chong-Kil
    • IMMUNE NETWORK
    • /
    • 제11권3호
    • /
    • pp.163-168
    • /
    • 2011
  • Background: Nanoparticles (NPs) prepared from biodegradable polymers, such as poly (D,L-lactic acid-co-glycolic acid) (PLGA), have been studied as vehicles for the delivery of antigens to phagocytes. This paper describes the preparation of antigen-loaded PLGA-NPs for efficient cross-priming. Methods: NPs containing a similar amount of ovalbumin (OVA) but different sizes were produced using a micromixer-based W/O/W solvent evaporation procedure, and the efficiency of the NPs to induce the cross-presentation of OVA peptides were examined in dendritic cells (DCs). Cellular uptake and biodistribution studies were performed using fluorescein isothiocyanate (FITC)-loaded NPs in mice. Results: The NPs in the range of $1.1{\sim}1.4{\mu}m$ in size were the most and almost equally efficient in inducing the cross-presentation of OVA peptides via $H-2K^b$ molecules. Cellular uptake and biodistribution studies showed that opsonization of the NPs with mouse IgG greatly increased the percentage of FITC-positive cells in the spleen and lymph nodes. The major cell type of FITC-positive cells in the spleen was macrophages, whereas that of lymph nodes was DCs. Conclusion: These results show that IgG-opsonized PLGA-NPs with a mean size of $1.1{\mu}m$ would be the choice of biodegradable carriers for the targeted-delivery of protein antigens for cross-priming in vivo.

항체의 Cyclic DTPA를 이용한 $^{99m}Tc$ 표지시 Polymer 형성과 체내 동태 변화 (Polymer Formation and Altered Biodistribution of IgG Labeled with $^{99m}Tc$ and Cyclic DTPA)

  • 임상무;우광선;정위섭;오옥두
    • 대한핵의학회지
    • /
    • 제27권2호
    • /
    • pp.270-276
    • /
    • 1993
  • $Technetium-^{99m}$ labeling method using bifunctional chelating agent cyclic DTPA has been evaluated with human polyclonal nonspecific IgG. IgG was conjugated with cyclic DTPA with various molar ratio. Reduction of $^{99m}Tc$ was done with $Na_2S_2O_4$ with various molar excess. Labeling efficiency and identification of polymer was confirmed with HPLC using TSK4000 SW column. Polymer was purified with 100 cm Sepharose 6LB column. Cultured $1{\times}10^9$ Staphylococcus aureus were injected into rat thigh 24 hours later labeled IgG was injected, and in vivo distribution was observed 4 and 24 hours thereafter. Reduction of $^{99m}Tc$ was optimal with the 10000-50000 times molar excess of $Na_2S_2O_4$. Polymer formation increased with increasing mloar excess of cyclic DTPA to IgG. Three step labeling-labeling DTPA conjugated IgG after reduction of $^{99m}Tc$-made more polymer than two two step labeling-simultaneous mixing DTPA conjugated IgG, $^{99m}Tc$ and $Na_2S_2O_4$. $^{99m}Tc$ blood clearance and lower uptake in the abscess and other organs. IgG conjugated with 200 times molar excess of cyclic DTPA showed slower blood clearance with 200 times molar excess of cyclic DTPA showed slower blood clearance than that of 200 times molar excess of cyclic DTPA showed slower blood clearance than that of 20 times molar excess. In the $^{99m}Tc$ labeling of IgG with cyclic DTPA for the immunoscintigraphy, obtimal labeling condition should be chosen, and effect of the $^{99m}Tc$ labeled IgG polymer should be considered.

  • PDF