Study provides an in-depth analysis of the structure-function relationship of polysaccharide anticancer drug carriers and points out benefits and potential drawbacks of differences in polysaccharide glycosidic bonding, branching and drug binding mode of the carriers. Cellulose, dextrin, dextran and hyaluronic acid have been regioselectively oxidized to respective dicarboxylated derivatives, allowing them to directly conjugate cisplatin, while preserving their major structural features intact. The structure of source polysaccharide has crucial impact on conjugation effectiveness, carrier capacity, drug release rates, in vitro cytotoxicity and cellular uptake. For example, while branched structure of dextrin-based carrier partially counter the undesirable initial burst release, it also attenuates the cellular uptake and the cytotoxicity of carried drug. Linear polysaccharides containing β-(1→4) glycosidic bonds and oxidized at C2 and C3 (cellulose and hyaluronate) have the best overall combination of structural features for improved drug delivery applications including potentiation of the cisplatin efficacy towards malignances.

• MeSH
• antitumorózní látky aplikace a dávkování   MeSH
• buňky NIH 3T3 MeSH
• celulosa chemie   MeSH
• cisplatina aplikace a dávkování   MeSH
• dextrany chemie   MeSH
• dextriny chemie   MeSH
• glykosidy chemie   MeSH
• inhibiční koncentrace 50 MeSH
• kyselina hyaluronová chemie   MeSH
• kyslík chemie   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• myši MeSH
• nosiče léků * MeSH
• oxidace-redukce MeSH
• platina chemie   MeSH
• polysacharidy chemie   MeSH
• systémy cílené aplikace léků * MeSH
• techniky in vitro MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The molecular weight (Mw) of dextran derivatives, such as regioselectively oxidized dicarboxydextran (DXA), is greatly influencing their faith in an organism, which could be possibly used to improve anticancer drug delivery. Here we present a modified method of sulfonation-induced chain scission allowing direct and accurate control over the Mw of DXA without increasing its polydispersity. Prepared DXA derivatives (Mw = 10-185 kDa) have been conjugated to cisplatin and the Mw of the carrier found to have a significant impact on cisplatin release rates, in vitro cytotoxicity, and migrastatic potential. Conjugates with the high-Mw DXA showed particularly increased anticancer efficacy. The best conjugate was four times more effective against malignant prostatic cell lines than free cisplatin and significantly inhibited the ovarian cancer cell migration. This was traced to the characteristics of spontaneously formed cisplatin-crosslinked DXA nanogels influenced by Mw of DXA and amount of loaded cisplatin.

• MeSH
• adenokarcinom farmakoterapie   metabolismus   MeSH
• antitumorózní látky chemie   farmakologie   MeSH
• buňky A549 MeSH
• cisplatina chemie   farmakologie   MeSH
• dextrany chemie   MeSH
• lidé MeSH
• molekulová hmotnost MeSH
• nádory prostaty farmakoterapie   metabolismus   MeSH
• nádory vaječníků farmakoterapie   metabolismus   MeSH
• nádory farmakoterapie   metabolismus   MeSH
• nanogely chemie   MeSH
• nosiče léků chemie   MeSH
• oxidace-redukce MeSH
• pohyb buněk účinky léků   MeSH
• systémy cílené aplikace léků metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH