Alginate hydrogels functionalized with β‐cyclodextrin as a local paclitaxel delivery system

• Published in: Journal of biomedical materials research. Part A 2021-12, Vol.109 (12), p.2625-2639
• Main Authors: Omtvedt, Line Aanerud, Kristiansen, Kåre Andre, Strand, Wenche Iren, Aachmann, Finn Lillelund, Strand, Berit Løkensgard, Zaytseva‐Zotova, Daria Sergeevna
• Format: Article
• Language: English
• Subjects: alginate; Alginates; Alginates - chemistry; Alginic acid; Antineoplastic Agents, Phytogenic - administration & dosage; beta-Cyclodextrins - chemistry; Cell Line, Tumor; Crystallization; Cyclodextrins; Cytotoxicity; Degradation; Degradation products; Drug delivery; drug delivery system; Drug Delivery Systems; Gel diffusion; Gels; Humans; hydrogel; Hydrogels; Hydrogels - chemistry; Inclusion complexes; Male; Mechanical Phenomena; Mechanical properties; Paclitaxel; Paclitaxel - administration & dosage; Polysaccharides; Prostate cancer; Rheological properties; Solubility; β-Cyclodextrin
• ISSN: 1549-3296; 1552-4965
• DOI: 10.1002/jbm.a.37255

Modification of drug delivery materials with beta‐cyclodextrins (β‐CyD) is known to increase solubility of poorly water‐soluble drugs, protect drugs from degradation and sustain release. In this study, we developed a hydrogel drug delivery system for local paclitaxel delivery using the natural polysaccharide alginate functionalized with β‐CyD‐moieties. Paclitaxel was chosen due to its ability to form inclusion complexes with cyclodextrins. The rheological and mechanical properties of the prepared hydrogels were characterized, as well as in vitro release of the paclitaxel and in vitro activity on PC‐3 prostate cancer cells. Introduction of β‐CyD‐moieties into the hydrogel reduces the mechanical properties of the gels compared to nonmodified gels. However, gelation kinetics were not markedly different. Furthermore, the β‐CyD‐modified alginate helped to reduce undesired crystallization of the paclitaxel in the gel and facilitated paclitaxel diffusion out of the gel network. Remarkably, the β‐CyD grafted alginate showed increased capacity to complex paclitaxel compared to free HPβ‐CyD. Release of both paclitaxel and degradation products were measured from the gels and were shown to have cytotoxic effects on the PC‐3 cells. The results indicate that functionalized alginate with β‐CyDs has potential as a material for drug delivery systems.