Routes of Administration: SC, IM, Oral, Intranasal, Topical

The route is part of the protocol, not a stylistic choice. Peptides are proteins or short chains of amino acids - most are destroyed by stomach acid before they can be absorbed orally, and most are too large to cross intact mucous membranes. The route options that survive those constraints are narrow, and pairing the wrong route to a compound is the most common way someone "ran the protocol" without producing the protocol's effects.

This article walks through five routes, who survives which, and where the catalogue compounds actually use each. For dose-volume math at the syringe, see Syringe, Draw and Dosage Math; for the SC site rotation logic, see Injection Rotation.

Subcutaneous (SC) - the default

• What it is. Injection into the fat layer just under the skin, depth 4–8 mm. Standard insulin-syringe needle is purpose- built for this - short, fine, integrated into the syringe.
• Bioavailability. Effectively 100% of the dose enters circulation, with absorption over 30 min – 2 h depending on the compound. Predictable, repeatable.
• Why it's the default. Cheap, simple, low pain, minimal training, suitable for almost every peptide. The pharmacokinetic profile (gradual absorption from the SC depot) suits both daily-cadence compounds and long-half-life weekly compounds equally well.
• Catalogue use. BPC-157, TB-500, all the GH-axis compounds (Mod GRF, Ipamorelin, CJC-1295, Sermorelin, Tesamorelin, Somatropin), all the GLP-1 family (Semaglutide, Tirzepatide, Retatrutide, Liraglutide), Melanotan II, PT-141, IGF-1 LR3, Thymosin Alpha-1 - i.e., almost everything injectable in the catalogue.
• Site rotation matters. Daily and BID protocols accumulate skin damage at fixed sites. See Injection Rotation Grid.

Intramuscular (IM) - when local or high-volume matters

• What it is. Injection into muscle tissue, depth 25–38 mm depending on muscle and body composition. Requires a longer needle (1 inch / 25 mm minimum, often 1.5 inch / 38 mm) and a separate Luer-lock syringe - not the standard insulin syringe.
• Why it sometimes makes a difference. Larger injection volumes (1+ mL) absorb better from muscle than from SC fat. Site-specific delivery (IGF-1 DES into a target muscle for local hypertrophy) requires IM placement. Some peptides have stability profiles that favour the muscle environment over SC fat.
• Why most peptides don't use it. Most catalogue doses are sub-mL volumes - SC works fine and is far less invasive. Adding IM injection trauma without a clear pharmacokinetic reason is cost without benefit.
• Catalogue use. IGF-1 DES (site-specific hypertrophy use case is the canonical IM indication). TB-500 sometimes IM for tendon-proximal injection sites. Most other "IM peptides" in forum culture are doing IM for no real reason; the SC route would work the same.
• Trauma is real. Bruising, post-injection muscle soreness, and risk of nerve / vessel proximity (especially glute-medial vs glute-max) make IM a higher-skill route. Read the target muscle's safe-zone literature before starting.

Oral - narrow but real

Most peptides are destroyed by gastric acid and pancreatic proteases before reaching systemic circulation. The compounds that survive oral administration are exceptional - they're either acid-stable by design, or they act locally in the gut and don't need systemic bioavailability.

• BPC-157 (oral). The "B" stands for "Body Protection Compound" - derived from a gastric-juice-stable region of human gastric protein. Survives the stomach intact. Oral BPC-157 is a real use case for gut-lining repair (IBD-pattern, post-NSAID, ulcer pattern); it's what oral BPC was designed for. Systemic SC BPC-157 is a different use case - local gut effect doesn't require systemic blood levels.
• KPV (oral). Alpha-MSH C-terminal tripeptide. Functions as an anti-inflammatory in gut tissue when given orally. Standard in gut-health protocols (often paired with oral BPC-157).
• Sublingual / buccal preparations. Some vendors sell "sublingual peptide" formulations claiming bypass of first-pass metabolism. The actual evidence for peptide absorption across oral mucosa is thin - sublingual peptide tablets are mostly marketing. Exceptions exist but they're product-specific (some semaglutide formulations are designed for oral mucosa absorption with permeation enhancers).
• Rybelsus (oral semaglutide). Pharmaceutical-grade oral semaglutide tablet that uses an absorption enhancer (SNAC) to cross the GI mucosa. Real bioavailability is ~1% - still useful but requires a 14 mg oral dose to deliver what a 0.5 mg SC injection delivers. See The Oral GLP-1 Era.

Intranasal - peptides that need to reach the brain

• What it is. Spray applied to the nasal mucosa. Absorption goes through the nasal epithelium directly into local circulation, with a partial direct-to-brain pathway via the olfactory nerve.
• Why it works for some peptides. Small peptides (under ~1 kDa) can cross the nasal mucosa intact. The olfactory-nerve pathway is the only non-injection route that bypasses the blood-brain barrier; for centrally-acting peptides this is meaningful bioavailability advantage.
• Catalogue use. Selank and Semax - the two Russian nootropic peptides. Both are 7-amino-acid peptides under the size threshold; both are designed around intranasal as the standard route. Bioavailability data is from Russian clinical literature; the onset (5–15 minutes) is consistent with the direct-pathway model. Melanotan II is occasionally given intranasally as an alternative to SC - works but gives a less reliable dose profile.
• What it doesn't work for. Larger peptides (most catalogue compounds). Nasal spray "BPC-157" or "TB-500" exists in some grey-market forms; absorption across the nasal mucosa for compounds >2 kDa is poor enough that the route is mostly placebo relative to SC.
• Storage matters. Reconstituted nasal-spray peptides are particularly fragile - small volumes, multiple sprays per day, and ambient-temperature exposure between uses degrade quickly. See Cold-Chain Reality.

Topical - GHK-Cu specifically

• What it is. Cream, serum, or solution applied to the skin. Most peptides are too large to cross the stratum corneum intact, but a few have either small-enough size or specific skin-receptor activity that makes topical effective.
• GHK-Cu is the canonical case. The copper-bound tripeptide is small (3 amino acids + Cu²⁺) and skin-receptor active. Decades of cosmetic-industry use, FDA-cleared in some product lines for wound healing, and a real evidence base for collagen upregulation, fibroblast activity, and wrinkle reduction at the topical application site. Standard formulations are 1–3% in serum or cream. See the Skin and Hair application for the full protocol.
• What else might work topically. Some smaller peptides (Argireline / acetyl hexapeptide-3, Matrixyl) are in cosmetic-industry use. Catalogue-relevant: not many. BPC-157 in topical preparations is a marketing claim with thin evidence - the molecule is too large to penetrate intact skin in any meaningful quantity.
• What doesn't work topically. Most everything else. GH-axis peptides, GLP-1s, IGF-1 family, melanocortin agonists for systemic effects - all need to be injected. Topical "transdermal" versions of these are marketing.

Bioavailability snapshot

Decision frame

1. Is the protocol you're running designed around a specific route?
   → Yes (most are) → use that route. Selank intranasal, MT-II SC, GHK-Cu topical, oral BPC-157 for gut. Don't deviate without a pharmacokinetic reason.
2. Is the goal local-tissue effect (gut repair, skin, target muscle)?
   → The local-route option exists for that goal - oral for gut, topical for skin, IM for site-specific muscle. Use it.
3. Do you need centrally-acting effect (cognitive, mood)?
   → Intranasal if the molecule supports it; otherwise SC and accept that BBB crossing is partial.
4. Is dose volume >1 mL per session?
   → IM is sometimes better tolerated than a large SC bolus. Catalogue peptides rarely hit this volume; usually a sign you should re-examine the concentration.
5. Default if none of the above apply?
   → Subcutaneous. The default is the default for a reason.

What stops people

• Treating route as a free choice. "I tried sublingual BPC because injection makes me nervous" usually produces a no-effect report. The route was the protocol; abandoning it didn't make the compound work via the new path.
• Believing nasal-spray marketing for large peptides. Nasal-spray BPC-157 / TB-500 / IGF-1 LR3 exists in grey-market products. The absorption isn't there. If the molecule is >2 kDa and it's offered intranasally, treat it as placebo until proven otherwise.
• Missing the local-vs-systemic distinction. Oral BPC-157 for gut repair and SC BPC-157 for tendon repair are different applications, not interchangeable. The route choice is part of which application you're targeting.
• IM injection without site research. Glute-max IM is forgiving; ventroglute, deltoid, vastus lateralis all have proximity to vessels and nerves that need attention. If you're doing IM, read the safe-zone literature for the specific muscle first.
• Topical creams as a substitute for systemic protocols. Topical GHK-Cu does meaningful skin work. It does not replace a GH-axis protocol for body composition. Different mechanisms, different routes, different applications.

Cross-references

• Syringe, Draw and Dosage Math - the at-the-syringe math that pairs with route selection.
• Injection Rotation - site management for daily SC protocols.
• The Oral GLP-1 Era - the Rybelsus / Orforglipron oral-GLP-1 case in depth.
• Skin and Hair application - the canonical topical use case (GHK-Cu).
• Gut Health application - where oral BPC-157 and KPV fit.
• Cognitive Focus application - the intranasal Selank and Semax protocols in context.