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Selectively Oxidized Cellulose with Adjustable Molecular Weight for Controlled Release of Platinum Anticancer Drugs
L. Münster, M. Fojtů, Z. Capáková, T. Vaculovič, M. Tvrdoňová, I. Kuřitka, M. Masařík, J. Vícha,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
Odkazy
PubMed
30794396
DOI
10.1021/acs.biomac.8b01807
Knihovny.cz E-zdroje
- MeSH
- antitumorózní látky * chemie farmakokinetika farmakologie MeSH
- buňky NIH 3T3 MeSH
- buňky PC-3 MeSH
- celulosa * chemie farmakokinetika farmakologie MeSH
- cisplatina * chemie farmakokinetika farmakologie MeSH
- koncentrace vodíkových iontů MeSH
- léky s prodlouženým účinkem chemie farmakokinetika farmakologie MeSH
- lidé MeSH
- myši MeSH
- nádorové mikroprostředí účinky léků MeSH
- nádory * farmakoterapie metabolismus patologie MeSH
- oxidace-redukce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The synthesis of selectively oxidized cellulose, 2,3-dicarboxycellulose (DCC), is optimized for preparation of highly oxidized material for biological applications, which includes control over the molecular weight of the product during its synthesis. Conjugates of DCC and cisplatin simultaneously offer a very high drug binding efficiency (>90%) and drug loading capacity (up to 50 wt %), while retaining good aqueous solubility. The adjustable molecular weight of the DCC together with variances in drug feeding ratio allows to optimize cisplatin release profiles from delayed (<2% of cisplatin released during 6 h) to classical burst release with more than 60% of cisplatin released after 24 h. The release rates are also pH-dependent (up to 2 times faster release at pH 5.5 than at pH 7.4), which allows to exploit the acidic nature of tumor microenvironment. Extensive in vitro studies were performed on eight different cell lines for two cisplatin-DCC conjugates with different release profiles. In comparison with free cisplatin, both cisplatin-DCC conjugates demonstrated considerably lower cytotoxicity toward healthy cells. Conjugates with burst release profiles were found more effective against prostate cell lines, while DCC conjugates with slower release were more cytotoxic against ovarian and lung carcinoma cell lines. In vivo studies indicated a significantly longer survival rate, a reduction in tumor volume, and a higher accumulation of platinum in tumors of mice treated with the cisplatin-DCC conjugate in comparison to those treated by free cisplatin.
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- $a The synthesis of selectively oxidized cellulose, 2,3-dicarboxycellulose (DCC), is optimized for preparation of highly oxidized material for biological applications, which includes control over the molecular weight of the product during its synthesis. Conjugates of DCC and cisplatin simultaneously offer a very high drug binding efficiency (>90%) and drug loading capacity (up to 50 wt %), while retaining good aqueous solubility. The adjustable molecular weight of the DCC together with variances in drug feeding ratio allows to optimize cisplatin release profiles from delayed (<2% of cisplatin released during 6 h) to classical burst release with more than 60% of cisplatin released after 24 h. The release rates are also pH-dependent (up to 2 times faster release at pH 5.5 than at pH 7.4), which allows to exploit the acidic nature of tumor microenvironment. Extensive in vitro studies were performed on eight different cell lines for two cisplatin-DCC conjugates with different release profiles. In comparison with free cisplatin, both cisplatin-DCC conjugates demonstrated considerably lower cytotoxicity toward healthy cells. Conjugates with burst release profiles were found more effective against prostate cell lines, while DCC conjugates with slower release were more cytotoxic against ovarian and lung carcinoma cell lines. In vivo studies indicated a significantly longer survival rate, a reduction in tumor volume, and a higher accumulation of platinum in tumors of mice treated with the cisplatin-DCC conjugate in comparison to those treated by free cisplatin.
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