Oral Peptides — What Works and What Does Not

ORAL BIOAVAILABILITY OF PEPTIDES: Most peptides >10 amino acids have negligible oral bioavailability (<1%) due to: (1) Gastric acid hydrolysis (pH 1-2 destroys peptide bonds). (2) Pepsin and pancreatic protease digestion. (3) Poor absorption across intestinal epithelium (too large, too hydrophilic). (4) First-pass hepatic metabolism. EXCEPTIONS: Cyclic peptides (cyclosporine — oral immunosuppressant), N-methylated peptides (improved permeability), very short peptides (di/tripeptides — absorbed by PepT1 transporter), lipophilic peptides, and formulations with absorption enhancers. SUBLINGUAL ADMINISTRATION: Placing peptide solution under the tongue allows absorption through the sublingual mucosa (thin epithelium with rich blood supply), bypassing GI degradation and first-pass metabolism. Bioavailability is typically 10-30% — better than swallowing but less than injection. Works for: small peptides, some bioregulators, BPC-157 (for oral cavity/throat applications), oxytocin. Revilab SL series products are specifically designed for sublingual delivery. TOPICAL ADMINISTRATION: Some peptides are applied to the skin — primarily cosmetic peptides (Matrixyl, Argireline, GHK-Cu) and wound-healing peptides (BPC-157 cream, TB-500 topical). Skin penetration is generally limited to the epidermis/dermis; systemic absorption is minimal.