Buccal delivery of small molecules and biologics: of mucoadhesive polymers, films, and nanoparticles

•The buccal route has been exploited for selected potent small molecules.•Research to achieve buccal insulin delivery is based on avoiding the GIT.•Buccal insulin clinical trials have led to variable results with no FDA approvals.•There is a rationale for buccal delivery of glucagon-like peptide 1 analogues.•Development of printed films is timely and offer an opportunity for complex systems.

Buccal delivery of macromolecules (biologics) sets a great challenge for researchers. Although several niche small molecule products have been approved as simple sprays, tablets and oral films, it is not simply a case of adapting existing technologies to biologics. Buccal delivery of insulin has reached clinical trials with two approaches: oromucosal sprays of the peptide with permeation enhancers, and embedded gold nanoparticles in a dissolvable film. However, neither of these approaches have led to FDA approvals likely due to poor efficacy, submaximal peptide loading in the dosage form, and to wide intra-subject variability in pharmacokinetics and pharmacodynamics. It is likely however that printed film designs with lower molecular weight stable biotech payloads including lipophilic glucagon-like 1 (GLP-1) agonists and macrocycles with long half-lives will generate greater efficacy than was achieved to date for insulin.

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