Table 1.

Characteristics of different administration routes for peptide/protein-based drugs

delivery route	challenges	benefits
parenteral	requires injections several times daily - inconvenient for patients – affects treatment compliance peptides rapidly metabolized or cleared from circulation Intramuscular (IM) and subcutaneous (SC) can lead to metabolic inactivation before reaching circulation lack of site specificity leads to side effects	avoids passing through the gastrointestinal tract (GIT) intravenous (IV) injection directly delivers to systemic circulation rapid onset of drug action
oral	biochemical and physical barrier: enzymatic hydrolysis and low pH in the gastrointestinal tract (GIT) intestinal epithelial membrane barrier: tight epithelial junctions more hydrophilic, charged surface– reduced ability to cross cellular membranes (lipophilic, no passive diffusion for highly hydrophilic molecules) mucus barrier prevents drug penetration and absorption, short residence time	non-invasive ease of administration
pulmonary	irritation of lung tissue possible immunogenicity (macrophages and IgG antibodies) mucus barrier can prevent drug penetration and absorption	ease of administration potential for high absorption rate high bioavailability rapid onset of action avoidance of oral administration problems
transdermal	tight epithelial junction skin irritation	ease of administration avoidance of oral administration problems
nasal	low membrane permeability for protein and peptide drugs poor tolerability of absorption enhancers in nasal cavity allergy/nasal related diseases can affect the efficiency of nasal drug delivery mucus barrier prevents drug penetration and absorption	rich vascular supply and the large surface area for absorption avoids metabolism and other problems with oral administration non-invasive nature