Uptake of Enzymatically-Digested Hyaluronan by Liver Endothelial Cells in Vivo and in Vitro

Mochizuki, Seibu; Kano, Arihiro; Shimada, Noritomo; Maruyama, Atsushi

doi:10.1163/156856208x393518

Cited by 18 publications

(14 citation statements)

References 47 publications

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“…These results are also supported by the fact that liver endothelial cells could take up HA both in vitro and in vivo. 16) Therefore, HA clearly has the ability to target liver endothelial cells. We next hypothesized that free HA coated liposomes could be accumulated to a greater extent in liver endothelial cells than non-coated liposomes, because free HA could be introduced on the surface of liposomes via electrostatic interactions.…”

Section: Discussionmentioning

confidence: 99%

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Synthesis and Evaluation of Stearylated Hyaluronic Acid for the Active Delivery of Liposomes to Liver Endothelial Cells

Toriyabe

Hayashi

Hyodo

et al. 2011

Biological & Pharmaceutical Bulletin

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Hyaluronic acid (HA) is a naturally-occurring ligand that can be useful for targeting liver endothelial cells. We describe herein the development of a new HA-lipid conjugate for the efficient delivery of liposomes to liver endothelial cells. When free HA coated cationic liposomes were injected into mice, their accumulation in the liver was significantly decreased depending on the content of free HA, while accumulation in the lung was not significantly changed. When cationic liposomes modified with HA-stearylamine (HA-SA conjugate) were injected in mice, liver accumulation was increased depending on the amount of HA-SA conjugate and accumulation in the lung was drastically reduced, compared to non-modified liposomes. Confocal imaging analyses showed that HA-SA modified liposomes were accumulated to a greater extent along with blood vessels than non-modified liposomes, suggesitng that HA-SA modified liposomes are distributed in endothelial cells in the liver. Collectively, these findings indicate that an HA-SA conjugate is a useful material that can be used to modify liposomes and for delivering bioactive liposomal cargoes to liver endothelial cells.

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Section: Discussionmentioning

confidence: 99%

“…16) Further studies are clearly needed for the more selective delivery to liver endothelial cells to be achieved by escaping uptake by kupffer cells. Optimization of the molecular weight of HA, and the use of a pH sensitive cationic lipid are some promising candidates.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Evaluation of Stearylated Hyaluronic Acid for the Active Delivery of Liposomes to Liver Endothelial Cells

Toriyabe

Hayashi

Hyodo

et al. 2011

Biological & Pharmaceutical Bulletin

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“…Fluorescein was covalently attached to 1.2 MDa HA according to the published procedure (Mochizuki et al, 2009), resulting in a fluorescein/HA disaccharide ratio of~0.02-0.03 as reported by the authors. Two different batches of flHA were used throughout this study.…”

Section: Flha Labeling and Functional Characterizationmentioning

confidence: 99%

A comprehensive model of hyaluronan turnover in the mouse

2012

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“…The same authors also reported that the total amount of excretion into bile within 24 hours was reported to be very low, 0.7% of the administered dose, and the total amount of excretion HA into feces, within 100 hours of administration, was also very small, about 0.5% of the administered dose (25) (25). Research on the effects of size and dose of fluorescein-labeled HA on its metabolism has shown that 60% of the tail vein injected 90 kDa HA accumulated in the liver , while both the 3 kDa and 10 kDa fluorescein-labeled HA were quickly excreted in urine with no accumulation in any tissues (31). As such, neither HA nor any other gadolinium based MRI agents administered intravenously are known to have any significant gastrointestinal uptake.…”

Section: Discussionmentioning

confidence: 99%

Molecular MR Imaging of CD44 in Breast Cancer with Hyaluronan-Based Contrast Agents

Artemov¹,

Zhu²

2009

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information , 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. (From -To) REPORT DATE (DD-MM-YYYY) 01-09-2009 REPORT TYPE Final DATES COVERED PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) AND ADDRESS(ES) PERFORMING ORGANIZATION REPORT NUMBERJohns Hopkins University Baltimore, Maryland 21205 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S)U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for public release SUPPLEMENTARY NOTES ABSTRACTWe have synthesized and characterized MR imaging agents using hyaluronic acid (HA) polymer backbones with molecular weights of 16, 31, and 74 kDa. The gadolinium content of HA-(EDA-DTPA-Gd) conjugates varied with preparations and was about ~10% as determined by ICP-MS, which corresponds to ~70% modification ratio of the HA carboxyl groups. T 1 values of HA-(EDA-DTPA-Gd) prepared from HA of molecular weight 16kD, 31kD, and 74kD and measured at 400MHz were very comparable in the range from 15.3 ms to 19 ms. We also synthesized fluorescent labeled HA probes using the same HA molecules and demonstrated efficient labeling of the polymer using anime-reactive dyes and EDC/EDA linker. Biodistribution of the HA-(EDA-DTPA-Gd) contrast agent in vivo was determined by T1 weighted MRI. Blood half-life time of HA-(EDA-DTPA-Gd) compounds was determined from changes in blood relaxivity as a function of time. Two-compartment pharmacokinetic model provided good fit of experimental data and for 16kDa HA compound the fast and slow phases life times were 12.4 min and 141 min, respectively. Preliminary data suggest an increased uptake of 16 kDa and 31 kDa HA-(EDA-DTPA-Gd) agents in CD44-positive MDA-MB-231 tumor xenografts in comparison to CD44-negative MCF-7 tumors. During the first year of the project we have synthesized and characterized MR imaging agents using hyaluronic acid (HA) polymer backbones with molecular weights of 16, 31, and 74 kDa. Briefly, HA (200 mg) was dissolved in 2-(N-Morpholino)ethanesulfonic acid buffer (MES 0.1 mol/L, 20 mL, pH 4.75). The carboxyl groups of hyaluronan were activated by the addition of 200mg EDC and 80mg N...

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Uptake of Enzymatically-Digested Hyaluronan by Liver Endothelial Cells in Vivo and in Vitro

Cited by 18 publications

References 47 publications

Synthesis and Evaluation of Stearylated Hyaluronic Acid for the Active Delivery of Liposomes to Liver Endothelial Cells

Synthesis and Evaluation of Stearylated Hyaluronic Acid for the Active Delivery of Liposomes to Liver Endothelial Cells

A comprehensive model of hyaluronan turnover in the mouse

Molecular MR Imaging of CD44 in Breast Cancer with Hyaluronan-Based Contrast Agents

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