Table I.

Advantages and disadvantages of administration routes for protein, peptide and antibody based therapeutics. Created from information provided in (28)

Route of administration	Advantages	Disadvantages
Parenteral	Intravenous route offers 100% bioavailability Rapid delivery of drug into systemic circulation Viable alternative if oral route is not feasible	Intravenous route is painful, invasive and poorly tolerated by patients Potential for toxic effects due to repeated administration
Oral	Painless Convenient	Potential for poor permeability across the intestinal epithelial membrane First pass metabolism Proteases present in the gastrointestinal tract may degrade drug
Pulmonary	Painless Large surface area available for protein absorption Avoids first pass metabolism Low enzyme activity in the lungs	Potential for poor permeability across epithelial lining fluid, epithelial cell layer and the endothelial membrane of capillary cells Proteins and peptides may be subjected to phagocytosis by the macrophages in the lungs
Ocular	Avoids first pass metabolism	Potential for poor permeability, particularly of hydrophilic macromolecules, across eye membrane High enzyme activity, i.e. protease and aminopeptidase
Nasal	Painless Large surface area available for protein absorption Avoids first pass metabolism Thin porous endothelial basement membrane of the nasal epithelium facilitates drug absorption	Potential for poor permeability, particularly of large hydrophilic macromolecules, across nasal epithelium Rapid mucociliary clearance that reduces the available time for drug absorption Only small amounts of drug can be administered via the nasal route
Rectal	Offers partial bypass of first pass metabolism	Potential for poor permeability across rectal epithelium Patient may consider this route distasteful
Transdermal	Painless Convenient Large surface area available for protein absorption Avoids first pass metabolism Potential for adaptability to deliver both small and macromolecular therapeutics, e.g. by using microneedles	Potential for poor permeability, particularly of large hydrophilic molecules, across the stratum corneum Potential for localised skin irritation