Synthesis and in vitro evaluation of cyclodextrin hyaluronic acid conjugates as a new candidate for intestinal drug carrier for steroid hormones

Steroid hormones became increasingly interesting as active pharmaceutical ingredients for the treatment of endocrine disorders. However, medical applications of many steroidal drugs are inhibited by their very low aqueous solubilities giving rise to low bioavailabilities. Therefore, the prioritized oral administration of steroidal drugs remains problematic. Cyclodextrins are promising candidates for the development of drug delivery systems for oral route applications, since they solubilize hydrophobic steroids and increase their rate of transport in aqueous environments. In this study, the synthesis and characterization of polymeric v-cyclodextrin derivates is described, which result from the attachment of a hydrophilic v-CD-thioether to hyaluronic acid. Host-guest complexes of the synthesized v-cyclodextrin hyaluronic acid conjugates were formed with two poorly soluble model steroids (v-estradiol, dexamethasone) and compared to monomeric v-cyclodextrin derivates regarding solubilization and complexation efficiency. The v-cyclodextrin-drug (host-guest) complexes were evaluated in vitro for their suitability (cytotoxicity and transport rate) as intestinal drug carriers for steroid hormones. In case of v-estradiol, higher solubilities could be achieved by complexation with both synthesized v-cyclodextrin derivates, leading to significantly higher intestinal transport rates in vitro. However, this success could not be shown for dexamethasone, which namely solubilized better, but could not enhance the transport rate significantly. Thus, this study demonstrates the biocompatibility of the synthesized and characterized v-cyclodextrin derivates and shows their potential as new candidate for intestinal drug carrier for steroid hormones like v-estradiol.