Mucoadhesive Electrospun Patches for the Delivery of Therapeutic Peptides and Proteins to the Oral Mucosa

Diseases of the oral mucosa are highly prevalent and can be debilitating. Treatment options are restricted by the limited range of therapeutic agents that can be delivered to the oral cavity using existing dosage forms, which offer little site-specificity and result in short exposure times. Fibrous mucoadhesive formulations prepared using electrospinning are promising for oral mucosal delivery because of their flexibility and high surface area, which allows them to adhere and efficiently deliver therapeutic agents to the affected tissue. This emerging technology has been investigated previously for a narrow range of conventional therapeutic agents. To expand the potential for novel therapies, this thesis has further developed the technology to allow the delivery of functional proteins, peptides, and antibody-based therapies. Lysozyme, bradykinin, and F(ab) antibody fragments were incorporated into polymeric mucoadhesive patch formulations that contained poly(vinyl pyrrolidone) and Eudragit® RS100 using electrospinning from ethanol/water solvent mixtures. These hydrophilic proteins were all eluted from the formulation over suitable timescales for oral mucosal delivery, within approximately 2 h. Proteins were stabilised by the polymer system during processing, resulting in highly conserved functionality. The formulation was investigated in greater detail for the delivery of cytokine-neutralising F(ab) antibody fragments to treat chronically inflamed autoimmune ulcers. Patches applied to tissue-engineered models of oral ulcers reduced detectable levels of key disease-causing molecules, providing the first experimental evidence that topical biologic therapies may be an effective treatment for oral diseases. Patches applied to tissue-engineered oral epithelia delivered a comparable dose of F(ab) to an equivalent dose in solution, providing preliminary evidence that patches may also be suitable for the systemic delivery of highly permeating peptides via the oral mucosa.