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Abstract
A combined hydrogel-based drug delivery system consisting of alginate and cucurbit[n]uril (Q[n]) was prepared for the delivery of albendazole (ABZ), a sparingly soluble anthelmintic recently found to have anti-cancer activity. Q[n] is a family of macrocyclic host molecules that has two roles in the delivery system described within this thesis. The smaller homologue, Q[5], served as an ionic cross-linker with two sodium ions bonded at both of its portals. The larger homologues, Q[7] and Q[8], encapsulated ABZ in their cavities. The encapsulation significantly increased the solubility of ABZ in water and achieved considerable drug loading content within the hydrogel, with a relatively high loading efficiency around 40%.
Precursor solutions were prepared by dissolving sodium alginate in saturated Q[5] solutions. Different amounts of the drug complexes were dissolved to give precursor solutions of different formulation. The hydrogel beads were best form by dripping the precursor solutions into a pH1 gelling solution. The beads exhibited the same pH responsive swelling behaviour as calcium alginate hydrogel.
Drug release studies were conducted in release media of low and high NaCl concentrations at three pH conditions of 6.3, 3 and 1. Percentage of the loaded drug released and drug release rates were found to be highly sensitive to the concentration of NaCl and pH but were also affected by other factors such as the type (size of the homologue used) and the amount of the drug complexes loaded into the gel. Complete release of the drug could be achieved only in the presence of ions, suggesting substantial electrostatic attraction between the drug complexes, the cross-linking Q[5] and the alginate.
Experimental drug release data were analysed by mathematical models, which suggested that drug release was primarily controlled by diffusion, with a swelling controlled component, where ions were present. The fitted effective diffusion coefficient of the drug complexes ranged between ~3×10-8 and 7×10-7 cm2/s, depending on the type and the amount of the drug complexes loaded and the nature of the release media.
It is proposed, based on the experimental results and the mathematical modelling, that both of the drug complexes formed aggregates with Q[5] through intermolecular interactions, which is a process initiated by electrostatic attraction. However, ABZ@Q[8] had stronger interactions and formed larger aggregates than ABZ@Q[7], and hence had a more retarded release.
Slow release of ABZ over a few days was achieved in physiological saline with ABZ@Q[8] and ABZ@Q[7] offered faster release maintaining higher concentrations.