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  • Title: Synthesis and evaluation of anti-fungal activities of sodium alginate-amphotericin B conjugates.
    Author: Ravichandran V, Jayakrishnan A.
    Journal: Int J Biol Macromol; 2018 Mar; 108():1101-1109. PubMed ID: 29126939.
    Abstract:
    Sodium alginate (SA) was oxidized using periodate and amphotericin B (AmB) was conjugated via imine and amine linkages to the oxidized alginate. Oxidization drastically reduced the molecular weight (MW) of the alginate. The conjugates were highly water-soluble to the extent of 1000mg/mL making them useful for therapeutic applications. SA-AmB conjugates derived from 20 and 50% oxidized alginate were non-toxic to HEK 293T and RAW 264.7 cell line at 100μg/mL and was also non-hemolytic to human blood at 100μg/mL. In vitro release of AmB into phosphate buffer from the imine conjugates was negligible with less than 0.2% of the drug released in 48h. Capping of residual aldehyde handles using 2-ethanolamine or glycine resulted in increased release of the drug in vitro. Injectable gels of gelatin crosslinked with oxidized alginate incorporating the SA-AmB conjugates as well as AmB were also fabricated and drug release was examined. In vitro release from the gel discs showed that AmB was released to the extent of 15-20% in 2days. The SA-AmB conjugates showed potent anti-fungal activity against C. albicans, C. neoformans and C. parapsilosis. The injectable gels seem to have potential for prolonged release of AmB when implanted.
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