The Experts below are selected from a list of 199530 Experts worldwide ranked by ideXlab platform
Leaf Huang - One of the best experts on this subject based on the ideXlab platform.
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effect of Liposome size on the circulation time and intraorgan distribution of amphipathic poly ethylene glycol containing Liposomes
Biochimica et Biophysica Acta, 1994Co-Authors: David C Litzinger, Antoinette M J Buiting, Nico Van Rooijen, Leaf HuangAbstract:Abstract Liposomes containing dioleoyl -N-( monomethoxypoly (ethylene glycol)succinyl)-phosphatidylethanolamine (PEG-PE), and of three characteristic sizes ( d > 300 nm , d ∼ 150–200 nm , and d nm ), were prepared, injected into mice, and their biodistributions examined following a radioactive lipid phase marker. The large and small Liposomes accumulated to elevated levels in spleen and liver, respectively. The intermediate sized Liposomes were found to be the longest circulating. Furthermore, when injected into mice bearing murine MC-38 colon carcinoma tumor, an approximate 2-fold increase in the % injected dose per g tumor was observed for the long-circulating Liposomes compared to Liposomes without PEG-PE. The distribution of the injected Liposomes within the tumor was examined by fluorescence microscopy, where the Liposomes were labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI). The Liposomes were found surrounding blood vessels in the tumor, with some degree of extravasation into the tumor mass. A previous explanation for the reduced circulation time of small Liposomes has been that they have an ability to pass through the fenestrated liver endothelium and thereby reach the parenchymal cells. DiI-labeled Liposomes were therefore used to examine the intrahepatic distribution of the injected Liposomes. Liposomes accumulated in liver were localized to Kupffer cells, regardless of Liposome size. The small Liposomes were not detectable in areas comprised of parenchymal cells when using this fluorescence technique. The reason for reduced long-circulating behavior for the small Liposomes may be more directly related to the activity of PEG-PE. Therefore the steric barrier activity of the Liposomes was examined by a serum protein binding assay and by streptavidin binding to biotinylated Liposomes. The steric barrier was Liposome size dependent, with the small Liposomes revealing increased protein binding. This decreased steric barrier of the small Liposomes may result in increased susceptibility to opsonization and thus explain their more rapid clearance from the circulation. The large Liposomes accumulated in spleen were localized in the red pulp and marginal zone. Uptake of the large Liposomes may occur by means of a filtration mechanism. These results establish the significance of Liposome size in determining Liposome circulation time and biodistribution, and are relevant for the optimal design of Liposomes for drug delivery.
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role of Liposome size and res blockade in controlling biodistribution and tumor uptake of gm1 containing Liposomes
Biochimica et Biophysica Acta, 1992Co-Authors: Atsuhide Mori, Leaf HuangAbstract:We have examined the effect of Liposome size on Liposome circulation time in the blood. Liposomes composed of phosphatidylcholine, cholesterol and ganglioside GM1 were prepared in the various size range. Optimal circulation activity (55% injected dose at 4 h post injection) of GM1-containing Liposomes, which correlated with a relatively high uptake of Liposomes by EMT6 tumor in mouse, was obtained with a size range of 70 to 200 nm in diameter. Increasing the diameter of Liposome to greater than 200 nm resulted in an enhancement of the spleen uptake and decrease of the blood level. For Liposomes with a diameter of less than 70 nm, 70% of the injected dose were taken up by the liver, presumably by the parenchymal cells. In contrast, the biodistribution of phosphatidylserine-containing Liposomes was relatively insensitive to changes in Liposome size; most of the injected dose was found in the liver. The effect of RES blockade on the circulation time of large (d > 300nm), GM1-containing Liposomes was also studied. Dextran sulfate 500, a commonly used blockade reagent for Kupffer cells, bad no effect. On the other hand, preinjection of a large dose of Liposomes with a diameter greater than 500 nm showed variable results depending on the lipid composition of the blocking Liposomes. Preinjection of Liposomes containing GM1, phosphatidylinositol or (N-polycthyleneglycol) phosphatidylethanolamine effectively reduced the spleen uptake of the large GM1-containing Liposomes, whereas Liposomes containing phosphatidic acid showed no effect. These results indicate that only spleen homing Liposomes can be used as a blocking reagent to prolong the circulation time of the large GM1-containing Liposomes.
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Size Homogeneity of a Liposome Preparation is Crucial for Liposome Biodistribution in Vivo
Journal of Liposome Research, 1992Co-Authors: Dexi Liu, Leaf HuangAbstract:AbstractSmall Liposomes, prepared by sonication or extrusion, were compared for their biodistribution patterns in mice. Significant difference was observed for a given lipid composition for Liposomes prepared by these two different methods. Using gel filtration, negative stain EM, and quasi-elastic light scattering analysis of the Liposome preparations, it appeared that such difference was resulted from the heterogeneity in Liposome size. Sonicated Liposomes, more heterogeneous in size, generally showed a lower uptake in the liver and spleen and higher level in the blood than the less heterogeneous extruded Liposomes.
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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
Biochimica et Biophysica Acta, 1991Co-Authors: Aleksander L Klibanov, Vladimir P Torchilin, Kazuo Maruyama, Anne Marie Beckerleg, Leaf HuangAbstract:Dioleoyl-N-(monomethoxy polyethyleneglycol succinyl)-phosphatidylethanolamine (PEG-PE) (mol. wt. of PEG= 5000), an amphipathic polymer, can be incorporated into the Liposome membrane and significantly prolong the blood circulation time of the Liposome. As little as 3.7 mol% of PEG-PE in Liposome resulted in maximal enhancement of Liposome circulation time. However, this activity of PEG-PE was only seen with relatively small Liposomes (d ≤ 200nm); larger Liposomes containing PEG-PE showed an unusually high level (approx. 35% injected dose) of accumulation in the spleen. We have tested whether the small, PEG-PE containing Liposomes are suitable for immuno targeting by incorporating a lung-specific monoclonal antibody on the Liposome surface. While another amphiphile, ganglioside GM1, which is well known for its activity to prolong the Liposome circulation time, significantly enhanced the lung binding of the immunoLiposomes, PEG-PE incorporation of immunoLiposomes resulted in a low level of target binding. To test if the reduced target binding is due to a steric barrier effect of the surface PEG polymer, we have incorporated a small amount of N-biotinaminocaproylphosphatidylethanolamine into the PEG-PE containing Liposomes and examined the Liposome agglutination induced by the addition of streptavidin. As little as 0.72 mol% PEG-PE in these Liposomes completely abolished agglutination. In contrast, incorporation of GM1 in Liposomes only reduced the rate, but not the extent, of Liposome agglutination. These results strongly support the hypothesis that PEG-PE prolongs Liposome circulation time by providing a strong steric barrier which prevents close contact with another Liposome or cell. Since GM1 provides only a weak steric barrier effect, its activity to prolong the Liposome circulation time must involve another yet unknown mechanism.
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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
Biochimica et Biophysica Acta, 1991Co-Authors: Aleksander L Klibanov, Vladimir P Torchilin, Kazuo Maruyama, Anne Marie Beckerleg, Leaf HuangAbstract:Dioleoyl-N-(monomethoxy polyethyleneglycol succinyl)-phosphatidylethanolamine (PEG-PE) (mol. wt. of PEG = 5000), an amphipathic polymer, can be incorporated into the Liposome membrane and significantly prolong the blood circulation time of the Liposome. As little as 3.7 mol% of PEG-PE in Liposome resulted in maximal enhancement of Liposome circulation time. However, this activity of PEG-PE was only seen with relatively small Liposomes (d less than or equal to 200 nm); larger Liposomes containing PEG-PE showed an unusually high level (approx. 35% injected dose) of accumulation in the spleen. We have tested whether the small, PEG-PE containing Liposomes are suitable for immuno targeting by incorporating a lung-specific monoclonal antibody on the Liposome surface. While another amphiphile, ganglioside GM1, which is well known for its activity to prolong the Liposome circulation time, significantly enhanced the lung binding of the immunoLiposomes, PEG-PE incorporation of immunoLiposomes resulted in a low level of target binding. To test if the reduced target binding is due to a steric barrier effect of the surface PEG polymer, we have incorporated a small amount of N-biotinaminocaproylphosphatidylethanolamine into the PEG-PE containing Liposomes and examined the Liposome agglutination induced by the addition of streptavidin. As little as 0.72 mol% PEG-PE in these Liposomes completely abolished agglutination. In contrast, incorporation of GM1 in Liposomes only reduced the rate, but not the extent, of Liposome agglutination. These results strongly support the hypothesis that PEG-PE prolongs Liposome circulation time by providing a strong steric barrier which prevents close contact with another Liposome or cell. Since GM1 provides only a weak steric barrier effect, its activity to prolong the Liposome circulation time must involve another yet unknown mechanism.
Marjeta Šentjurc - One of the best experts on this subject based on the ideXlab platform.
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Development of Liposome encapsulated clindamycin for treatment of acne vulgaris
Pflügers Archiv - European Journal of Physiology, 2000Co-Authors: Lidija Honzak, Marjeta ŠentjurcAbstract:The enhancement of topical delivery of hydrophilic substances by use of multilammelar Liposomes was measured ex vivo on pig ear skin and in vivo on hairless mice by electron paramagnetic resonance method (EPR). Multilamellar Liposomes with different lipid composition (final concentration of membrane components is 48 mg/ml) were loaded with a hydrophilic spin probe GluSL, which does not penetrate the Liposome membrane easily. They were characterized with respect to their stability, entrapped volume and enhancement characteristics. We observed significant differences in the properties of different types of Liposomes with respect to their stability when in contact with the skin and their penetration into the skin. The results measured in vivo are consistent with those obtained ex vivo. On the basis of these findings the Liposomes with appropriate stability and intradermal penetration characteristics were chosen for the development of Liposome-encapsulated 1% clindamycin preparation for therapy of acne vulgaris. A double-blind clinical study was conducted to assess the safety and efficiency of Liposome-encapsulated 1% clindamycin solution versus 1% clindamycin solution (Klimicin^® T, Lek). On the basis of the clinical trial it may be concluded that Liposome-encapsulated 1% clindamycin solution was therapeutically superior over conventional 1% clindamycin solution in the treatment of acne vulgaris
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Influence of hydrogels on Liposome stability and on the transport of Liposome entrapped substances into the skin
International Journal of Pharmaceutics, 1995Co-Authors: V. Gabrijelčič, Marjeta ŠentjurcAbstract:Different Liposome-hydrogel formulations, which are used for topical application of Liposomes, have been prepared and the role of hydrophilic polymers on the transport of Liposome-entrapped hydrophilic substance into pig ear skin was investigated by one-dimensional electron paramagnetic resonance imaging (1D-EPRI) and reduction kinetic imaging methods. Using conventional EPR the influence of polymers on Liposome stability was also determined. Multilamellar Liposomes composed basically of hydrogenated soya lecithin and cholesterol, with the entrapped hydrophilic paramagnetic probe ASL (N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)-N-dimethyl-N-hydroxyethylammonium iodide), were prepared in water solution and then mixed into hydrogels with different concentrations of hydrophilic polymers: carboxymethylcellulose or xanthan gum. It was found that the polymers examined do not prevent efficient transport of Liposome-entrapped substances into the skin. From the on-going stability study of Liposomes in hydrogel formulations, it follows that carboxymethycellulose does not influence the stability of Liposomes during the time course of 6 weeks, while in xanthan hydrogels leakage of Liposome-entrapped hydrophilic substance was observed already after 10 days. The results support the use of hydrogels in Liposome dermatics, but it should be taken into account that some hydrophilic polymers can influence the physical stability of Liposomes appreciably.
Arto Urtti - One of the best experts on this subject based on the ideXlab platform.
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Topical drug delivery to retinal pigment epithelium with microfluidizer produced small Liposomes.
European Journal of Pharmaceutical Sciences, 2014Co-Authors: Tatu Lajunen, K. Hisazumi, Takanori Kanazawa, Hiroaki Okada, Yasuo Seta, Marjo Yliperttula, Arto Urtti, Yuuki TakashimaAbstract:Abstract Drug delivery from topically instilled eye drops to the posterior segment of the eye has long been one of the greatest challenges of ocular drug development. We developed methods of Liposome preparation utilizing a microfluidizer to achieve adjustable nanoparticle size (even less than 80 nm) and high loading capacity of plasmid DNA. The microfluidizing process parameters were shown to affect the size of the Liposomes. Higher operating pressures and passage for at least 10 times through the microfluidizer produced small Liposomes with narrow size distribution. The Liposomes were physically stable for several months at +4 °C. In vivo distribution of the optimized Liposome formulations in the rat eyes was investigated with confocal microscopy of the histological specimens. Transferrin was used as a targeting ligand directed to retinal pigment epithelium. Size dependent distribution of Liposomes to different posterior segment tissues was seen. Liposomes with the diameter less than 80 nm permeated to the retinal pigment epithelium whereas Liposomes with the diameter of 100 nm or more were distributed to the choroidal endothelium. Active targeting was shown to be necessary for Liposome retention to the target tissue. In conclusion, these microfluidizer produced small Liposomes in eye drops are an attractive option for drug delivery to the posterior segment tissues of the eye.
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interaction of Liposomes with human skin in vitro the influence of lipid composition and structure
Biochimica et Biophysica Acta, 1996Co-Authors: Merja Kirjavainen, Arto Urtti, Ilpo Jaaskelainen, Marjukka T Suhonen, Petteri Paronen, Riitta Valjakkakoskela, Juha Kiesvaara, Jukka MonkkonenAbstract:Abstract Liposomes have been suggested as a vehicle for dermal and transdermal drug delivery, but the knowledge about the interaction between lipid vesicles and human skin is poor. Therefore, we visualized Liposome penetration into the human skin by confocal laser scanning microscopy (CLSM) in vitro. Liposomes were prepared from phospholipids in different compositions and labeled with a fluorescent lipid bilayer marker, N-Rh-PE ( l -α-phosphatidylethanolamine-N-lissamine rhodamine B sulfonyl). Fluorescently labelled Liposomes were not able to penetrate into the granular layers of epidermis. However, the fluorescence from Liposome compositions containing DOPE (dioleylphosphatidyl ethanolamine) was able to penetrate deeper into the stratum corneum than that from Liposomes without DOPE. Pretreatment of skin with unlabeled Liposomes containing DOPE or lyso-phosphatidyl choline (lyso-PC) enhanced the subsequent penetration of the fluorescent markers, N-Rh-PE and sulforhodamine B into the skin, suggesting possible enhancer activity, while most Liposomes did not show such enhancement. Resonance energy transfer (RET) and calcein release assay between stratum corneum lipid Liposomes (SCLLs) and the phospholipid vesicles suggested that the Liposomes containing DOPE may fuse or mix with skin lipids in vitro and loosen the SCLL bilayers, respectively. Among the factors not affecting stratum corneum penetration were: negative charge, cholesterol inclusion and acyl chain length of the phospholipids. In conclusion, fusogenicity of the Liposome composition appears to be a prerequisite for the skin penetration.
Tianshun Lian - One of the best experts on this subject based on the ideXlab platform.
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trends and developments in Liposome drug delivery systems
Journal of Pharmaceutical Sciences, 2001Co-Authors: Tianshun Lian, Rodney J. Y. HoAbstract:Abstract Since the discovery of Liposomes or lipid vesicles derived from self‐forming enclosed lipid bilayers upon hydration, Liposome drug delivery systems have played a significant role in formulation of potent drugs to improve therapeutics. Currently, most of these Liposome formulations are designed to reduce toxicity and to some extent increase accumulation at the target site(s) in a number of clinical applications. The current pharmaceutical preparations of Liposome‐based therapeutics stem from our understanding of lipid–drug interactions and Liposome disposition mechanisms including the inhibition of rapid clearance of Liposomes by controlling size, charge, and surface hydration. The insight gained from clinical use of Liposome drug delivery systems can now be integrated to design Liposomes targeted to tissues and cells with or without expression of target recognition molecules on Liposome membranes. Enhanced safety and heightened efficacy have been achieved for a wide range of drug classes, including antitumor agents, antivirals, antifungals, antimicrobials, vaccines, and gene therapeutics. Additional refinements of biomembrane sensors and Liposome delivery systems that are effective in the presence of other membrane‐bound proteins in vivo may permit selective delivery of therapeutic compounds to selected intracellular target areas. © 2001 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:667–680, 2001
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trends and developments in Liposome drug delivery systems
Journal of Pharmaceutical Sciences, 2001Co-Authors: Tianshun LianAbstract:Since the discovery of Liposomes or lipid vesicles derived from self-forming enclosed lipid bilayers upon hydration, Liposome drug delivery systems have played a significant role in formulation of potent drugs to improve therapeutics. Currently, most of these Liposome formulations are designed to reduce toxicity and to some extent increase accumulation at the target site(s) in a number of clinical applications. The current pharmaceutical preparations of Liposome-based therapeutics stem from our understanding of lipid-drug interactions and Liposome disposition mechanisms including the inhibition of rapid clearance of Liposomes by controlling size, charge, and surface hydration. The insight gained from clinical use of Liposome drug delivery systems can now be integrated to design Liposomes targeted to tissues and cells with or without expression of target recognition molecules on Liposome membranes. Enhanced safety and heightened efficacy have been achieved for a wide range of drug classes, including antitumor agents, antivirals, antifungals, antimicrobials, vaccines, and gene therapeutics. Additional refinements of biomembrane sensors and Liposome delivery systems that are effective in the presence of other membrane-bound proteins in vivo may permit selective delivery of therapeutic compounds to selected intracellular target areas.
Yuuki Takashima - One of the best experts on this subject based on the ideXlab platform.
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Topical drug delivery to retinal pigment epithelium with microfluidizer produced small Liposomes.
European Journal of Pharmaceutical Sciences, 2014Co-Authors: Tatu Lajunen, K. Hisazumi, Takanori Kanazawa, Hiroaki Okada, Yasuo Seta, Marjo Yliperttula, Arto Urtti, Yuuki TakashimaAbstract:Abstract Drug delivery from topically instilled eye drops to the posterior segment of the eye has long been one of the greatest challenges of ocular drug development. We developed methods of Liposome preparation utilizing a microfluidizer to achieve adjustable nanoparticle size (even less than 80 nm) and high loading capacity of plasmid DNA. The microfluidizing process parameters were shown to affect the size of the Liposomes. Higher operating pressures and passage for at least 10 times through the microfluidizer produced small Liposomes with narrow size distribution. The Liposomes were physically stable for several months at +4 °C. In vivo distribution of the optimized Liposome formulations in the rat eyes was investigated with confocal microscopy of the histological specimens. Transferrin was used as a targeting ligand directed to retinal pigment epithelium. Size dependent distribution of Liposomes to different posterior segment tissues was seen. Liposomes with the diameter less than 80 nm permeated to the retinal pigment epithelium whereas Liposomes with the diameter of 100 nm or more were distributed to the choroidal endothelium. Active targeting was shown to be necessary for Liposome retention to the target tissue. In conclusion, these microfluidizer produced small Liposomes in eye drops are an attractive option for drug delivery to the posterior segment tissues of the eye.
