Doxorubicin-loaded delta inulin conjugates for controlled and targeted drug delivery: Development, characterization, and in vitro evaluation

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Doxorubicin-loaded delta inulin conjugates for controlled and targeted drug delivery: Development, characterization, and in vitro evaluation

Wang, Lixin (författare): University of South Australia

Song, Yunmei (författare): University of South Australia

Parikh, Ankit (författare): University of South Australia

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Joyce, Paul, 1989 (författare): Chalmers tekniska högskola,Chalmers University of Technology

Chung, Rosa (författare): University of South Australia

Liu, Liang (författare): University of South Australia

Afinjuomo, Franklin (författare): University of South Australia

Hayball, John D. (författare): University of South Australia,University of Adelaide

Petrovsky, Nikolai (författare): Flinders University of South Australia

Barclay, Thomas G. (författare): University of South Australia

Garg, Sanjay (författare): University of South Australia

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(creator_code:org_t)

2019-11-06
2019
Engelska.
Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 11:11

Relaterad länk:: https://research.cha... (primary) (free); visa fler...; https://www.mdpi.com...; https://research.cha...; https://doi.org/10.3...; visa färre...

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Abstract Ämnesord

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Delta inulin, also known as microparticulate inulin (MPI), was modified by covalently attaching doxorubicin to its nanostructured surface for use as a targeted drug delivery vehicle. MPI is readily endocytosed by monocytes, macrophages, and dendritic cells and in this study, we sought to utilize this property to develop a system to target anti-cancer drugs to lymphoid organs. We investigated, therefore, whether MPI could be used as a vehicle to deliver doxorubicin selectively, thereby reducing the toxicity of this antibiotic anthracycline drug. Doxorubicin was covalently attached to the surface of MPI using an acid-labile linkage to enable pH-controlled release. The MPI-doxorubicin conjugate was characterized using FTIR and SEM, confirming covalent attachment and indicating doxorubicin coupling had no obvious impact on the physical nanostructure, integrity, and cellular uptake of the MPI particles. To simulate the stability of the MPI-doxorubicin in vivo, it was stored in artificial lysosomal fluid (ALF, pH 4.5). Although the MPI-doxorubicin particles were still visible after 165 days in ALF, 53% of glycosidic bonds in the inulin particles were hydrolyzed within 12 days in ALF, reflected by the release of free glucose into solution. By contrast, the fructosidic bonds were much more stable. Drug release studies of the MPI-doxorubicin in vitro, demonstrated a successful pH-dependent controlled release effect. Confocal laser scanning microscopy studies and flow cytometric analysis confirmed that when incubated with live cells, MPI-doxorubicin was effciently internalized by immune cells. An assay of cell metabolic activity demonstrated that the MPI carrier alone had no toxic effects on RAW 264.7 murine monocyte/macrophage-like cells, but exhibited anti-cancer effects against HCT116 human colon cancer cells. MPI-doxorubicin had a greater anti-cancer cell effect than free doxorubicin, particularly when at lower concentrations, suggesting a drug-sparing effect. This study establishes that MPI can be successfully modified with doxorubicin for chemotherapeutic drug delivery.

Ämnesord

NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

Anticancer therapy
Targeted delivery
Advax
pH sensitive
Intracellular drug release
Doxorubicin
Inulin

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Av författaren/redakt...: Wang, Lixin; Song, Yunmei; Parikh, Ankit; Joyce, Paul, 198 ...; Chung, Rosa; Liu, Liang; visa fler...; Afinjuomo, Frank ...; Hayball, John D.; Petrovsky, Nikol ...; Barclay, Thomas ...; Garg, Sanjay; visa färre...

Om ämnet

NATURVETENSKAP: NATURVETENSKAP; och Biologi; och Cellbiologi

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Cell och molekyl ...

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Farmakologi och ...

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Av lärosätet: Chalmers tekniska högskola

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