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In Vitro Cell Toxic...
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Kullenberg, FredrikUppsala universitet,Institutionen för farmaceutisk biovetenskap
(author)
In Vitro Cell Toxicity and Intracellular Uptake of Doxorubicin Exposed as a Solution or Liposomes : Implications for Treatment of Hepatocellular Carcinoma
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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2021-07-06
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MDPI,2021
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-452937
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-452937URI
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https://doi.org/10.3390/cells10071717DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Cytostatic effects of doxorubicin in clinically applied doses are often inadequate and limited by systemic toxicity. The main objective of this in vitro study was to determine the anti-tumoral effect (IC50) and intracellular accumulation of free and liposomal doxorubicin (DOX) in four human cancer cell lines (HepG2, Huh7, SNU449 and MCF7). The results of this study showed a correlation between longer DOX exposure time and lower IC50 values, which can be attributed to an increased cellular uptake and intracellular exposure of DOX, ultimately leading to cell death. We found that the total intracellular concentrations of DOX were a median value of 230 times higher than the exposure concentrations after exposure to free DOX. The intracellular uptake of DOX from solution was at least 10 times higher than from liposomal formulation. A physiologically based pharmacokinetic model was developed to translate these novel quantitative findings to a clinical context and to simulate clinically relevant drug concentration-time curves. This showed that a liver tumor resembling the liver cancer cell line SNU449, the most resistant cell line in this study, would not reach therapeutic exposure at a standard clinical parenteral dose of doxorubicin (50 mg/m(2)), which is serious limitation for this drug. This study emphasizes the importance of in-vitro to in-vivo translations in the assessment of clinical consequence of experimental findings.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Degerstedt, OliverUppsala universitet,Institutionen för farmaceutisk biovetenskap(Swepub:uu)olide461
(author)
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Calitz, CarlemiUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)carca775
(author)
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Pavlovic, NatasaUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)natpa200
(author)
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Balgoma, DavidUppsala universitet,Analytisk farmaceutisk kemi(Swepub:uu)davba557
(author)
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Gråsjö, Johan,1962-Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Institutionen för läkemedelskemi,Farmaceutisk fysikalisk kemi(Swepub:uu)jgr13120
(author)
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Sjögren, Erik,1977-Uppsala universitet,Institutionen för farmaceutisk biovetenskap(Swepub:uu)ersjo473
(author)
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Hedeland, MikaelUppsala universitet,Analytisk farmaceutisk kemi(Swepub:uu)mikahede
(author)
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Heindryckx, FemkeUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)femhe402
(author)
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Lennernäs, HansUppsala universitet,Institutionen för farmaceutisk biovetenskap(Swepub:uu)hanslenn
(author)
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Uppsala universitetInstitutionen för farmaceutisk biovetenskap
(creator_code:org_t)
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In:Cells: MDPI10:72073-4409
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Calitz, Carlemi
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Pavlovic, Natasa
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Balgoma, David
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Sjögren, Erik, 1 ...
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- MEDICAL AND HEALTH SCIENCES
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Cells
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Uppsala University