• KSBB Journal
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• 제10권4호
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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.

• 한국식품영양과학회지
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• 제30권3호
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• pp.421-425
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• 2001

Antioxidative effects of crude chlorophylls and carotenoids extracts from mustard leaf kimchi on the lipid peroxidation in rat liver homogenate, egg phosphatidyl choline (EPC) liposome and superoxide anion radical were examined. The extracts were found to inhibit the increase of the thiobarbituric acid (TBA) value and show the effect of antioxidative activity on the liposomal phospholipid membrane. The oxidation index of EPC liposome was markedly decreased in the prescence of the extracts. The antioxidative activity of the extracts from mustard leaf kimchi was not related with fermentation period of the kimchi. The extracts from mustard leaf showed the similar antioxidative activity of $\alpha$-tocopherol within in the given level of addition. However, the oxidation index. When the effect of the extracts from mustard leaf kimchi on free radical scavenging was observed by the determination of the superoxide anion radical scavenging activity, it had similar value to that of $\alpha$-tocopherol.

• 생명과학회지
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• 제12권2호
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• pp.121-128
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• 2002

세포막 유동성은 생체의 항상성 유지의 가장 기본적이며 중요한 기능으로서, 도라지의 용매별 분획물의 첨가로 세포막 유동성에 미치는 영향을 열시차 열량분석법 (differential scanning calorimetry, DSC)으로 측정하였다. DPPC liposome에 도라지의 용매별 분획물 첨가시 첨가물의 농도 증가에 따라 서서히 상전이 온도가 저하되었고 thermogram도 넓어졌으며 이에 따라 협동 단위($\Delta$ $H_{vH}$ /$\Delta$ $H_{cal}$)수도 감소됨을 알 수 있었다. 이는 도라지 분획물의 첨가로 DPPC liposome의 유동성이 증가하였음을 보여주는 결과로 생각 되어진다. 시료의 각 용매별 분획물의 유동성 효과는 ethyl-ether 분획층인 PGMEE의 경우 상전이온도 Tm이 시료첨가 최고농도에서 DPPC liposome 만의 경우보다 4.3$^{\circ}C$가 저하되어 다른 분획물보다 그 정도가 두드러졌으며 그 순서는 hexane 분획층 PGMH, ethylacetate 분획층인 PGMEA 및 methanol 분획층 PGMM의 순이었으며 butanol 층인 PGMB는 그 효과가 미미하여 앞서의 열역학적 요소에 거의 영향을 미치지 못했다. 이와 같은 결과는 PGMB를 제외한 시료의 각 분획물 성분 중 분자내 hydrophobicity가 큰 물질들이 DPPC liposome 이중층의 소수성부분에 더 깊숙히 침투됨으로써 인지질 liposome의 유동성을 증가시킨 현상이라고 생각된다. 도라지의 용매별 분획물의 막유동성 증가는 이온, 약물, 영양물의 흡수, 수송 및 교환등 생체막의 주요기능에 영향을 미치므로 막유동성을 증가시키는 도라지 분획물들의 생리활성물질에 대한 더욱 구체적인 연구가 기대되어 진다.

• 한국식품영양과학회지
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• 제31권3호
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• pp.506-510
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• 2002

본 연구는 불포화 인지질인 DLPC liposome에 도라지(Platycodon grandiflorum A. DC, PG)의 용매별 분획물 일정 량을 가하고, 산화제 benzoyl peroxide를 가한 후 시료의 항산화 작용을 비교 분석하였다. 도라지 용매별 추출물 중 ethylether 분획물인 PGMEE와 ethylacetate 분획물인 PGMEA는 $\alpha$-tocopherol의 경우 보다 훨씬 그 산화지수가 낮아두 분획물에 의한 강한 항산화력을 측정할 수 있었으며, 잘알려진 강력한 항산화제인 BHT(butylated hydroxytoluence)의 경우와 비슷한 항산화 효과를 나타내었다. 한편 PGMEE 분획층에 비타민 C를 일정량을 첨가함으로서 상호 보강 작용에 의한 항산화 상승효과를 본 결과, Vit C를 첨가하지 않았을 때보다 산화지수가 횔씬 낮아졌다. BHT 함유의 DLPC liposome의 경우도 Vit C에 의한 비슷한 추과를 나타내었다. 이상의 결과에 의하여 도라지의 PGMEE 분획층에는 BHT와 비슷한 강한 항산화 효과를 가진 물질의 존재가 분명하다고 사료되며 비타민 C 첨가로 인한 항산화 상승 효과도 본 연구결과에 의해 뚜렷이 알 수 있었다. 이와 같은 연구에 의해 여러 질병들의 원인이 될 뿐만 아니라 세포막 손상을 일으키는 활성 산소 또는 유리기의 생성억제 등 균형된 식생활을 통한 식품 섭취의 중요성이 매우크다고 인식되며 특히 식품으로서 애용되고 있는 도라지의 인지질 세포막에 미치는 항산화 효과가 식품으로서 약이 되는 기전 규명에 기초자료가될 것을 바라는 바이다.

• Archives of Pharmacal Research
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• 제28권5호
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• pp.626-635
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• 2005

Liposome as a carrier of topotecan (TPT), a promising anticancer drug, has been reported in attempt to improve the stability and antitumor activity of TPT. However, the biodistr ibution pattern of TPT liposome in vivo and PEG-modified liposome containing TPT have not been studied systemically. In this paper, the in vitro stability and in vivo biodistribution behavior of several liposomes containing TPT with different lipid compositions and PEG-modification were studied. Compared with the 'fluid' liposome (S-Lip) composed of soybean phosphatidylcholine (SPC), the 'solid' liposome (H-Lip) composed of hydrogenated soybean phosphatidylcholine HSPC decreased the leaking efficiency of TPT from liposome and enhanced the stability of liposome in fetal bovine serum (FBS) or human blood plasma (HBP). The results of biodistribution studies in S$_{180}$ tumor-bearing mice showed that liposomal encapsulation increased the concentrations of total TPT and the ratio of lactone form in plasma. Compared with free TPT, S-Lip and H-Lip resulted in 5- and 19- fold increase in the area under the curve (AUC$_{0\rightarrow\propto}$), respectively. PEG- modified H-Lip (H-PEG) showed 3.7-fold increase in AUC$_{0\rightarrow\propto}$ compared with H-Lip, but there was no significant increase in t$_{1/2}$ and AUC$_{0\rightarrow\propto}$ for PEG-modified S-Lip (S-PEG) compared with S-Lip. Moreover, the liposomal encapsulation changed the biodistribution behavior, and H-Lip and H-PEG dramatically increased the accumulation of TPT in tumor, and the relative tumor uptake ratios were 3.4 and 4.3 compared with free drug, respectively. There was also a marked increase in the distribution of TPT in lung when the drug was encapsulated into H-Lip and H-PEG. Moreover, H-PEG decreased the accumulation of TPT in bore marrow compared with unmodified H-Lip. All these results indicated that the membrane fluidity of liposome has an important effect on in vitro stability and in vivo biodistribution pattern of liposomes containing TPT, and PEG-modified 'solid' liposome may be an efficient carrier of TPT.

• KSBB Journal
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• 제29권1호
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• pp.36-41
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• 2014

Skin disease is one of the most common diseases and its incidence is increasing dramatically in modern society. Specially, many attempts have been made to treat chronic skin inflammation diseases, such as psoriasis and atopic dermatitis, but effective therapies for the immune cell-mediated skin diseases, including psoriasis and atopic dermatitis have not been developed. Until recently, several drug candidates which were claimed to be effective for skin diseases have been reported, but most of them are not used to treat chronic skin disease. Especially, Psoriasis is characterized by excessive growth and aberrant differentiation of keratinocytes, but is fully reversible with appropriate therapy. The trigger of the keratinocyte response is thought to be activation of the cellular immune system, with T cells and various immune-related cytokines. Formation of new blood vessels starts with early psoriatic changes and disappears with disease clearance. Several angiogenic mediators are up-regulated in psoriasis development. Contact- and mediator-dependent factors derived from keratinocytes, mast cells and immune cells may contribute to the strong blood vessel formation of psoriasis. New technologies and experimental models provide new insights into the role of angiogenesis in psoriasis pathogenesis. TMP and its derivatives themselves effectively inhibited in vitro cell migration, tube formation, and the expression of angiogenic factors. However, TMP and its derivatives induced side effects including hemolysis and local side effects. Therefore, in an attempt to reduce the toxicity and the undesirable side effects of TMP and derivatives, a liposomal formulation was prepared and tested for its effectiveness. TMP and derivatives liposomes retained the effectiveness of TMP in vitro while side effects were reduced. These results support the conclusion that TMP effectively inhibits in vitro angiogenesis, with the possibility that use as a psoriasis relief agent.

• 한국식품영양과학회지
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• 제30권4호
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• pp.646-650
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• 2001

본 연구는 세포막의 유동성이 막의 항상성(homeostasis)을 유지하는 가장 기본적이며 중요한 성질이라는 점을 감안하여, 용매별로 분획한 식품의 추출물을 첨가함으로써 인지질 이중층(liposome)의 물리.화학적 성질에 미치는 막 유동성(membrane fluidity)의 변화를 열시차 열량 분석법(differential scanning calorimeter, DSC)에 의해 측정하였다. 즉 식탁의 애용식품인 당근의 용매별 분획물이 인지질 liposome에 미치는 막의 유동성에 미치는 증가효과를 본 결과, DPPC liposome에 당근의 용매별 분획물을 첨가했을 때, 일반적으로 첨가하지 않은 경우보다 첨가 농도의 증가에 따라 의존적으로 초기 상전이온도가 낮아졌고 흡열고선의 모양이 넓어졌으며 그로 인하여 협동단위($\Delta$$H_{VH}$ $\Delta$H㎈)값이 감소됨을 확인하였다. 이와 같은 현상은 일정농도의 당근분획물의 첨가가 DPPC liposome의 막유동성을 증가시킨 결과로 생각되어진다. 그리고 각 용매별 당근분획물의 유동성효과를 각각 비교해본 결과, DCSMH와 DCSMEA의 분획물첨가가 DCSMB와 DCSMA에 비해 DPPC liposome의 초기 상전이온도 및 협동단위를 더욱더 감소시켜 막유동성에 더 많은 영향을 주는 것을 확인하였다. 이와 같은 현상은 DCSMH와 DCSMEA의 분획물이 DCSMB와 DCSMA분획물의 경우보다 hydrophobicity가 더 크므로 인해 DPPC 인지질막 이중층의 acylchain쪽으로 더 깊숙히 용해하여 침투되므로서 생긴 현상이라 하겠다. 즉 당근분획물의 막유동성 증가작용은 세포막에서 일어나는 대사물, 약물, 이온 등의 운반 및 영양물의 교환, 흡수 등 생체막의 주요기능에 영향을 미치는 효과가 있는 것으로 사료되며, 앞으로 막유동성을 증가시키는 구체적 생리활성물질의 추구가 기대되어진다.