Cyclodextrin/dextran based drug carriers for a controlled release of hydrophobic drugs in zebrafish embryos

Abstract

Hydrogel-based drug carriers have been developed from biocompatible materials, cyclodextrin, dextran and poly(ethylene glycol) and were used in zebrafish embryos. Maleimide modified dextrans (Dex-mal) were functionalized with cyclodextrins and crosslinked to form a hydrogel using either per-6-thio-β-cyclodextrin (PSCD) or a combination of mono-6-thio-β-cyclodextrin (MSCD) and di-thiolated poly(ethylene glycol) (DSPEG). Using all-trans retinoic acid (RA) as a model hydrophobic drug, a sustained release from these cyclodextrin modified hydrogels was observed in vitro without an initial burst. This is because the cyclodextrin moiety in these hydrogels acts as a binding site for the RA. Furthermore, the nanosized hydrogel particles were injected into early stage zebrafish embryos in order to test in vivo release of RA and biocompatibility. We found the gel particles prepared from Dex-mal, MSCD and DSPEG were suitable for use in zebrafish embryos and it showed the release of RA in the embryos occurs in a controlled manner.