Explore studies of oral peptides.
Oral GHRP-2 (5-10 mg/kg) stimulated significant GH release in 1-month-old goats (peak at 15 min) but not in 3-month-old goats, demonstrating age-dependent oral peptide bioavailability in ruminants.
Hashizume, T; Kawai, M; Ohtsuki, K; Ishii, A; Numata, M · Animal Study
Oral GHRP-2 stimulated GH release in adult goats when absorbed through the intestines (not rumen), demonstrating post-gastric oral peptide bioactivity in adult large animals with mature digestive systems.
Hashizume, T; Tanabe, Y; Ohtsuki, K; Mori, A; Matsumoto, N; Hara, S · Animal Study
Oral thymosin alpha-1 enhanced T-cell function, NK cell activity, and cytokine production in mice, demonstrating that the peptide retains immunomodulatory activity after oral administration — a practical advance for non-injectable immune therapy.
Chen, Xiang-Ming; Jiang, Han-Liang; Zhou, Lin-Fu; Pan, Xiao-Ping; Hu, Zhong-Rong; Liu, Rong-Hua; Chen, Xiao-Ming; Chen, Zhi · Animal Study
Researchers developed a systematic method to create cyclic peptides that can be taken orally — solving one of the biggest challenges in peptide drug development. Their approach combined two strategies: (1) N-methylation of the peptide backbone to improve intestinal permeability, and (2) protecting charged groups with lipophilic prodrug modifications to allow absorption. They applied this to create an orally bioavailable RGD-containing hexapeptide that selectively binds the integrin αvβ3 — a receptor involved in tumor blood vessel growth. The final compound showed biological effects in mice after oral administration, proving the concept works in a living organism. The method involved screening combinatorial libraries for permeability, then systematically optimizing for receptor selectivity and oral absorption.
Weinmüller, Michael; Rechenmacher, Florian; Kiran Marelli, Udaya; Reichart, Florian; Kapp, Tobias G; Räder, Andreas F B; Di Leva, Francesco Saverio; Marinelli, Luciana; Novellino, Ettore; Muñoz-Félix, José M; Hodivala-Dilke, Kairbaan; Schumacher, Adi; Fanous, Joseph; Gilon, Chaim; Hoffman, Amnon; Kessler, Horst · Basic Science (Peptide Chemistry + Animal Proof Of Concept)
Exenatide is a peptide drug given by injection because it is destroyed in the gut and cannot cross the intestinal wall. Hydrophobic ion pairing (HIP) makes peptides lipophilic by pairing them with surfactant counterions. Two surfactant types were tested: cationic THA (tetraheptylammonium bromide) and anionic DOC (sodium docusate). Both formed stable complexes with exenatide. Exenatide-THA was more lipophilic (log D of 2.29 in simulated intestinal fluid vs 1.2 for exenatide-DOC). When loaded into lipid nanocarriers (41% Capmul MCM, 15% Captex 355, 40% Cremophor RH, 4% propylene glycol), the THA formulation showed: - 10-fold enhancement in intestinal apparent membrane permeability vs free exenatide - 28.0% ± 5.2% relative oral bioavailability in healthy rats The DOC formulation achieved 3-fold permeability enhancement and 16.3% ± 6.6% bioavailability. Neither formulation caused significant hemolytic activity at 0.25% concentration, indicating safety for oral use.
Ismail, Ruba; Phan, Thi Nhu Quynh; Laffleur, Flavia; Csóka, Ildikó; Bernkop-Schnürch, Andreas · Pharmaceutical Formulation + Animal Pharmacokinetics
Molecular grafting of bioactive epitopes into cyclotide scaffolds produces GPCR ligands with improved oral activity, enzymatic stability, and selectivity compared to linear peptide counterparts.
Muratspahić, Edin; Koehbach, Johannes; Gruber, Christian W; Craik, David J · Review
Pro-Hyp is a low molecular weight growth-initiating factor that selectively triggers proliferation of p75NTR-positive (stem cell-like) fibroblasts on collagen gel but not p75NTR-negative fibroblasts. Oral collagen/gelatin delivers Pro-Hyp to tissues and accelerates wound healing in animals and humans.
Sato, Kenji; Asai, Tomoko T; Jimi, Shiro · Review
Oral octreotide using TPE technology achieved therapeutic endpoints in Phase III trials with ~0.7% relative oral bioavailability, requiring 20 mg capsules compared to 0.1 mg subcutaneous injections.
Brayden, David J; Maher, Sam · Review
Oral semaglutide 14mg reduced total daily ad libitum energy intake by 38.9% versus placebo (treatment difference -5,096 kJ, p=0.0001). Increased satiety and fullness after fat-rich breakfast. Body weight decreased 2.7 kg (mostly fat mass) vs 0.1 kg placebo.
Gibbons, Catherine; Blundell, John; Tetens Hoff, Søren; Dahl, Kirsten; Bauer, Robert; Baekdal, Tine · Randomized Controlled Trial
Lipophilic salt forms of octreotide in lipid-based formulations improved enzymatic stability in GI lumen and intestinal membrane permeability, addressing both major barriers to oral peptide delivery.
Li, Peng; Ford, Leigh; Haque, Shadabul; McInerney, Mitchell P; Williams, Hywel D; Scammells, Peter J; Thompson, Philip E; Jannin, Vincent; Porter, Christopher J H; Benameur, Hassan; Pouton, Colin W · Preclinical
Oral delivery of peptide drugs faces three main barriers: enzymatic degradation (stomach acid and enzymes break them apart), poor membrane permeability (they are too large and charged to cross the gut lining), and instability (they unfold and lose function). Computer-aided drug design (CADD) addresses these by modeling molecular interactions at the atomic level. Researchers can simulate how a peptide interacts with its receptor, screen formulation ingredients for compatibility, and predict which chemical modifications might improve stability or absorption. The review highlights that CADD can pre-screen excipients (inactive ingredients in the formulation) and predict absorption before expensive lab experiments. This speeds up development and reduces costs for oral peptide formulations.
Pandya, Anjali K; Patravale, Vandana B · Review
Oral semaglutide reduced HbA1c by 0.85% in naive patients, 0.67% in DPP-4i switchers, and 0.13% in GLP-1 RA switchers.
Oya, Junko; Shimizu, Mika; Kubota, Ryo; Suda, Rika; Nagkagami, Tomoko · Retrospective Cohort
Oral semaglutide produced significant short-term reductions in HbA1c and body weight, along with improvements in cardiovascular risk markers, in a real-world type 2 diabetes population.
Palazzi, Sara; Sentinelli, Federica; Zugaro, Antonella; Morgante, Sara; Santarelli, Livia; Melanzi, Sandra; De Mutiis, Annamaria; Piersanti, Deamaria; Macerola, Barbara; Iezzi, Marco; Mercuri, Pietro; Ferranti, Alessandro; Tienforti, Daniele; Cavallo, Maria Gisella; Barbonetti, Arcangelo; Baroni, Marco Giorgio · Observational