Activity of amphipathic poly(ethylene glycol) 5000 to prolong the circulation time of liposomes depends on the liposome size and is unfavorable for immunoliposome binding to target

Klibanov, A.L.; Maruyama, Kazuo; Beckerleg, Anne Marie; Torchilin, Vladimir P.; Huang, Leaf

doi:10.1016/0005-2736(91)90385-l

Cited by 458 publications

(206 citation statements)

References 12 publications

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“…This result is agreement with findings of a previous report in which R8-modified carriers with diameters less than 200 nm accumulated in the liver more efficiently than in the spleen [26,27]. The cause of this phenomenon may be explained by the previous reports showing that the liposome size affects the biodistribution after the systemic injection of the carriers [29,30]. In that study, liposomes containing ganglioside GM1 with a diameter in excess of 300 nm were trapped by splenic macrophages and disappeared in the blood circulation, while the optimal size range of liposomes for a high blood concentration were from 70 to 200 nm [30].…”

Section: Discussionsupporting

confidence: 93%

Mitochondrial delivery of Coenzyme Q10 via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver

Yamada

Nakamura

Abe

et al. 2015

Journal of Controlled Release

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We herein report on a mitochondrial therapeutic effect based on the delivery of coenzyme Q10 (CoQ10), an anti-oxidant, to in vivo mitochondria using a MITO-Porter, a liposome-based mitochondrial delivery system that functions via membrane fusion. To evaluate the effects, we used a mouse liver ischemia/reperfusion injury (I/R injury) model, in which mitochondrial reactive oxygen species are overexpressed. We packaged CoQ10 in the lipid phase of a MITO-Porter and optimized the mitochondrial fusogenic activities to produce the CoQ10-MITO-Porter. A histological observation of the carriers in the liver by confocal laser scanning microscopy was done and the accumulation of the carrier labeled with a radio isotope in the liver confirmed that the CoQ10-MITO-Porter was delivered to liver mitochondria via systemic injection. These analytical results permitted us to optimize the compositions of the CoQ10-MITO-Porter so as to permit it to efficiently accumulate in mouse liver mitochondria.Finally, we applied the optimized CoQ10-MITO-Porter to mice via tail vein injection, and hepatic I/R injury was then induced, followed by measuring serum alanine aminotransferase (ALT) levels, a marker of liver injury. We confirmed that the use of the CoQ10-MITO-Porter resulted in a significant decrease in serum ALT levels, indicating that in vivo mitochondrial delivery of the CoQ10 via MITO-Porter prevents I/R injury in mice livers. This provides a demonstration of the potential use of such a delivery system in mitochondrial therapies.

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Section: Discussionsupporting

confidence: 93%

Mitochondrial delivery of Coenzyme Q10 via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver

Yamada

Nakamura

Abe

et al. 2015

Journal of Controlled Release

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“…the reticuloendothelial system (RES) and to enhance the blood retention profile (Klibanov et al, 1990(Klibanov et al, , 1991Allen, 1994;Gabizon etal, 1996;Lasic, 1996). Polyethylene glycol-tagged liposomal adriamycin (Doxil s ) has recently been reported as a clinical success (Orditura etal, 2004).…”

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confidence: 99%

Cisplatin-incorporating polymeric micelles (NC-6004) can reduce nephrotoxicity and neurotoxicity of cisplatin in rats

et al. 2005

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In spite of the clinical usefulness of cisplatin (CDDP), there are many occasions in which it is difficult to continue the administration of CDDP due to its nephrotoxicity and neurotoxicity. We examined the incorporation of CDDP into polymeric micelles to see if this allowed the resolution of these disadvantages. Cisplatin was incorporated into polymeric micelles through the polymer -metal complex formation between polyethylene glycol poly(glutamic acid) block copolymers and CDDP (NC-6004). The pharmacokinetics, pharmacodynamics, and toxicity studies of CDDP and NC-6004 were conducted in rats or mice. The particle size of NC-6004 was approximately 30 nm, with a narrow size distribution. In rats, the area under the curve and total body clearance values for NC-6004 were 65-fold and one-nineteenth the values for CDDP (Po0.001 and 0.01, respectively). In MKN-45-implanted mice, NC-6004 tended to show antitumour activity, which was comparable to or greater than that of CDDP. Histopathological and biochemical studies revealed that NC-6004 significantly inhibited the nephrotoxicity of CDDP. On the other hand, blood biochemistry revealed transient hepatotoxicity on day 7 after the administration of NC-6004. Furthermore, rats given CDDP showed a significant delay (Po0.05) in sensory nerve conduction velocity in their hind paws as compared with rats given NC-6004. Electron microscopy in rats given CDDP indicated the degeneration of the sciatic nerve, but these findings were not seen in rats given NC-6004. These results were presumably attributable to the significantly reduced accumulation of platinum in nerve tissue when NC-6004 was administered (Po0.05). NC-6004 preserved the antitumour activity of CDDP and reduced its nephrotoxicity and neurotoxicity, which would therefore seem to suggest that NC-6004 could allow the long-term administration of CDDP where caution against hepatic dysfunction must be exercised.

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“…And prolongation of liposome circulation in the bloodstream and passive targeting to tumor has been achieved by PEG modification of the liposome surface. [4][5][6][7][8][9][10][11] Furthermore, PEG modification around liposomes gives high stability: about a few years at room temperature, high blood circulation, and longer blood half time. In the case of using PEG as a liposome modifying material, PEG should have a hydrophobic anchor for interaction with phospholipids of a liposomal membrane.…”

Section: Introductionmentioning

confidence: 99%

Change in the Character of Liposomes as a Drug Carrier by Modifying Various Polyethyleneglycol-Lipids

Sugiyama

Sadzuka

2013

Biological & Pharmaceutical Bulletin

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When liposomes, as a superior drug carrier, are injected intravenously, active liposomes as medicines require polyethyleneglycol (PEG) as a modification tool around the liposomal membrane. PEG modification of a liposome forms a fixed aqueous layer, and the trapping by cells of the reticuloendothelial system (RES) is avoided. Hence, PEG-modified liposomes have long circulation in the bloodstream, and passive targeting to tumors has been achieved by PEG modification. We have been studying the passive targeting by liposomes with the expectation of more usefulness. It was proved a correlation between the PEG molecular weight of PEG-modified liposomes and blood circulation time and antitumor effect, too. Liposomes modified by PEG2000 were useful for uptake into tumor cells. We thought that the re-uptake in the liposomal membrane also increased accumulation. Moreover, it was proved that mixing two different PEGs to modify the liposome surface gives a bigger fixed aqueous layer thickness (FALT) around the liposome, giving the liposome strong antitumor activity. Then, we designed a novel PEG-lipid, 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-PEG (different double arms PEG; DDA-PEG), which had two different PEGs (2000 and 500) in one molecule. One of the innovative characteristics of DDA-PEG-modified liposome (DDAL) is that it heightens the contact ability with tumor cells. DDAL may be an effective DDS carrier for solving various PEG dilemmas. It was observed that passive targeting by PEG-modified liposomes had different characteristics by changing PEG length, anchor type or those combination. Thus, it should be applied to liposomes suitable for various diseases.

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Activity of amphipathic poly(ethylene glycol) 5000 to prolong the circulation time of liposomes depends on the liposome size and is unfavorable for immunoliposome binding to target

Cited by 458 publications

References 12 publications

Mitochondrial delivery of Coenzyme Q10 via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver

Mitochondrial delivery of Coenzyme Q10 via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver

Cisplatin-incorporating polymeric micelles (NC-6004) can reduce nephrotoxicity and neurotoxicity of cisplatin in rats

Change in the Character of Liposomes as a Drug Carrier by Modifying Various Polyethyleneglycol-Lipids

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