beta-Cyclodextrin-end-capped oligo(4-acryloylmorpholine) as amphiphilic drug carrier

β-Cyclodextrin-end-capped oligo(4-acryloylmorpholine) (β-CD-PACM) is a tadpole-shaped drug carrier in which the β-CD ring is the hydrophilic head and the PACM chain the amphiphilic tail β-CD-PACM is biocompatible, non-cytotoxic and non-hemolytic. One of its most interesting features is the ability to complex lipophilic drugs and to improve their bioavailability and stability through the non–covalent interaction with the β-CD. The oligomeric chain might cooperate with the β-CD moieties in stabilizing the complexes via secondary interactions with the guest molecule. The synthesis of β-CD-PACM of controlled molecular weight consists in the radical polymerization of 4-acryloylmorpholine (ACM) in the presence of 6-deoxy-6-mercapto-β-cyclodextrin (β-CD-SH) as chain-transfer agent. Their average molecular weight is in the order of 104. The chain-transfer constant (CT) of β-CD-SH in ACM radical polymerization is about 1.30 (close to 1), therefore the molecular weight of the β-CD-PACM does not appreciably vary on conversion. The chain transfer (β-CD-SH) is obtained by saponification of 6-deoxy-6-thioacetic-β-cyclodextrin, in turn prepared by exchange reaction between β-CD-tosylate and potassium thioacetate. Finally, the monotosylation reaction of β-CD is performed in aqueous alkaline medium at room temperature with simple cation exchange resin purification. Different biological studies were performed with this kind of drug carrier. An example is 4-hydroxynonenal (HNE), which is a promising new molecule in anticancer therapy, but it has low bioavailability due to insolubility in water, extreme reactivity and rapid degradation by specific enzymes. The complexation with β-CD-PACM enhances HNE’s stability and potentiates its antitumor effects in several tumor cell lines and in a human reconstructed skin carrying melanoma tumor cells.