Where a drug enters the body decides which barriers it meets first. Each route — oral, injected, inhaled, through the skin or nose — has its own speed, bioavailability and limits on what a carrier can do.
- Main routes
- Oral, IV, SC/IM, pulmonary, transdermal, nasal
- IV bioavailability
- 100% by definition
- Oral peptide bioavailability
- Typically < 1–2%
The route of administration is chosen as early as the target. It sets the onset of action, the fraction of dose that reaches the bloodstream (bioavailability), the dosing frequency and how acceptable the treatment is to patients.
Enteral routes (oral, sublingual, rectal) are convenient but expose the drug to stomach acid, digestive enzymes, the intestinal epithelium and first-pass metabolism in the liver. Parenteral routes (intravenous, subcutaneous, intramuscular) bypass the gut but need injection. Mucosal and topical routes — lungs, nose, eye, skin — offer local action or rapid absorption across thin barriers.
Delivery systems are designed around the route: enteric coatings and permeation enhancers for oral peptides, depots for subcutaneous injection, respirable particles for the lungs, microneedles for the skin and mucoadhesive systems for the nose.
Barriers along each route
Gastrointestinal tract
pH from 1.5 to 7.5, proteases, mucus and a tight epithelium, followed by first-pass liver metabolism.
Blood and vasculature
Plasma proteins, immune cells and rapid renal or hepatic clearance after intravenous dosing.
Skin (stratum corneum)
A 10–20 µm lipid–keratin barrier that lets through mainly small, lipophilic molecules under ~500 Da.
Lungs and nose
Mucociliary clearance and alveolar macrophages, offset by a huge, thin absorptive surface and direct nose-to-brain pathways.
How it works
- 1
Define the target site
Local action (lung, eye, skin) or systemic exposure decides whether the route must reach the blood.
- 2
Match the molecule
Size, stability and potency narrow the options — large or fragile molecules usually need injection or a protective carrier.
- 3
Engineer the carrier
Coatings, particle size, mucoadhesion or depot formation adapt the formulation to the route's barriers.
- 4
Consider the patient
Dosing frequency, self-administration and chronic use drive adherence and real-world outcome.
Routes compared
| Route | Onset | Bioavailability | Key advantage | Key limitation |
|---|---|---|---|---|
| Oral | 30–90 min | Variable, often low | Convenient, non-invasive | GI degradation and first-pass metabolism |
| Intravenous | Seconds | 100% | Complete, controlled dosing | Needs clinical setting; rapid clearance |
| Subcutaneous | Minutes–hours | 50–100% | Self-injection, depots possible | Limited volume (~1–2 mL) |
| Intramuscular | Minutes | High | Vaccines and long-acting injectables | Painful; limited volume |
| Pulmonary | Minutes | Moderate | Local lung action, large surface | Particle size must be 1–5 µm |
| Transdermal | Hours | Low–moderate | Steady release, avoids first pass | Only small lipophilic drugs passively |
| Intranasal | Minutes | Variable | Fast; possible nose-to-brain route | Small volume; mucociliary clearance |
Delivery technologies by route
| Route | Carrier or technology |
|---|---|
| Oral | Enteric coatings, self-emulsifying systems, permeation enhancers, mucoadhesive nanoparticles |
| Injectable | Liposomes, lipid nanoparticles, PLGA microspheres, in situ forming gels |
| Pulmonary | Dry-powder inhalers, nebulised liposomes, porous particles |
| Transdermal | Patches, microneedles, iontophoresis, nanoemulsions |
| Nasal / ocular | Mucoadhesive gels, chitosan nanoparticles, in situ gelling drops |
Strengths
- Patient-friendly options. Oral, inhaled and transdermal systems avoid needles and support chronic use.
- Local targeting. Delivering directly to lungs, eye or skin lowers systemic dose and side effects.
- Bypassing first pass. Parenteral, transdermal and sublingual routes avoid liver metabolism.
- Long-acting injectables. Depots extend dosing intervals from daily to monthly or longer.
Challenges
- Oral biologics. Peptides, proteins and nucleic acids are largely destroyed or excluded in the gut.
- Variable absorption. Food, disease and individual physiology change exposure for non-IV routes.
- Device dependence. Inhalers and microneedles add device design, cost and user technique.
- Volume limits. Subcutaneous and nasal routes restrict how much drug can be given at once.
Where it is used
mRNA vaccines
Intramuscular LNPs give local expression and draining-lymph-node exposure.
Oral semaglutide
A permeation enhancer enables a peptide tablet for diabetes.
Inhaled antibiotics
Liposomal amikacin reaches infected lung tissue at high local concentration.
Hormone patches
Transdermal systems deliver steady levels of oestradiol, nicotine or fentanyl.
What comes next
The goal is to bring injectable-only medicines to more convenient routes without losing exposure.
Oral biologics
Self-orienting capsules, enhancers and protective nanoparticles for peptides and antibodies.
Microneedle patches
Painless, self-administered vaccines and biologics that may not need cold chain.
Inhaled genetic medicines
Nebulised mRNA and siRNA nanoparticles for lung disease.
Nose-to-brain delivery
Using olfactory and trigeminal pathways to bypass the blood–brain barrier.
The route defines the first and often hardest barrier — good delivery design starts by matching molecule, carrier and route to where the drug must act and how patients will use it.