Abstract by Jianfei Huang
Polyelectrolyte complexes (PECs) of polycations and polyanions, formed through electrostatic interaction, have been used as the matrix of formulations for drug delivery. However, the strong interactions between the oppositely charged polyelectrolytes or drug substances in PECs may retard drug release from the formulations. Graphene oxide (GO) is an oxidized derivative of graphene and has good mechanical property. The aim of the current PhD project was to investigate the effect of GO and the composition of excipients in PEC buccal formulations on the release and antifungal activities of clotrimazole. Different buccal formulations were prepared using cationic chitosan and anionic alginate in the presence/absence of GO, and the study was focused on the molecular interactions occurring between clotrimazole and the excipients during the preparation and evaluation processes for formulations.
The buccal films, foams and hydrogels were successfully prepared by the same mixing process of the excipients and clotrimazole via probe sonication, followed by different casting and drying processes for the films and foams. The properties of the buccal formulations depended on the preparation conditions including the preparation methods, the mixing processes, the chitosan/alginate ratio and the GO content. The mechanical properties of the buccal formulations were evaluated for both the buccal films and the foams. The results showed that the ratio between chitosan and alginate of PECs in the matrix affected the mechanical properties of the buccal films, that is, more chitosan in the PECs matrix improved the strength of the films. Incorporation of GO in the PECs matrix made the buccal films and foams mechanically stronger.
The in vitro drug release study showed that both GO and the composition of PEC matrix affected the release of clotrimazole from the buccal formulations. Addition of 0.04 - 1 wt% GO in the buccal films and foams increased drug release from the buccal formulations. More drug was released from the buccal foams with a chitosan/alginate ratio of 1:3 than those with a chitosan/alginate ratio of 3:1 after 24 h. Dosage forms also affected the drug release. Clotrimazole was released faster from the hydrogels than from the films and the foams containing the same amount of GO, indicating that water molecules in the hydrogel decreased the diffusion obstacles for clotrimazole by disrupting the ionic interactions between the excipients and the clotrimazole molecules.
The in vitro antifungal activity study showed different effect of GO in the buccal films and foams. Addition of 0.04 wt% GO in the buccal films with clotrimazole resulted in an increase of activity against Candida albicans in vitro. However, when using up to 1 wt% GO, addition of GO in the buccal foams with drug didn’t affect the antifungal activity. Therefore, an appropriate amount of GO in the formulations may be required to enhance the antifungal effect of the formulations.
The preliminary in vivo data has proved that the principle for the buccal formulation with clotrimazole is a viable local delivery strategy for antifungal treatment.
In summary, this thesis has given new insight towards application and understanding of GO in the PEC buccal formulations for the antifungal drug clotrimazole.