Pharmacokinetics describes what the body does to a drug — absorption, distribution, metabolism and excretion. A carrier rewrites each of those steps, so the drug's fate becomes the carrier's fate until the payload is released.
- Framework
- ADME
- Key parameters
- Cmax, AUC, t½, Vd, CL
- Main nanoparticle sinks
- Liver and spleen
Pharmacokinetics (PK) quantifies how drug concentrations change over time in blood and tissues. Biodistribution describes where the dose goes. Together they link the dose to the exposure that produces effect and toxicity.
For a free small molecule, PK is governed by its own properties: it distributes widely, is metabolised by liver enzymes and is excreted by the kidney or bile, often within hours. Once encapsulated, the drug follows the carrier's PK: circulation is set by particle size, surface coating and protein adsorption; distribution is dominated by the mononuclear phagocyte system in liver and spleen; and release rate decides when the drug becomes free again.
Measuring this correctly means separating total, encapsulated and released drug, and tracking the carrier itself — by radiolabel, fluorescence or the expressed product of a nucleic acid payload.
ADME through a carrier
Absorption
Route and carrier decide how much of the dose reaches the circulation and how fast.
Distribution
Size, charge and stealth coating set which organs take up the carrier; the volume of distribution often shrinks.
Metabolism
Encapsulation shields the drug from enzymes and nucleases until release.
Excretion
Particles above ~6–8 nm avoid kidney filtration and are cleared by liver and spleen, extending half-life.
How it works
- 1
Dose and sample
Administer the formulation and collect blood and tissues at timed points.
- 2
Quantify
LC-MS/MS, qPCR, ELISA, radioactivity or imaging measure drug, carrier and payload expression.
- 3
Model
Non-compartmental or compartmental analysis gives Cmax, AUC, half-life, clearance and volume of distribution.
- 4
Link to effect
PK/PD and physiologically based (PBPK) models connect exposure to efficacy and safety, and guide human dose.
Key pharmacokinetic parameters
| Parameter | Meaning | Effect of a stealth nanocarrier |
|---|---|---|
| Cmax | Peak concentration | Lower peak of free drug, reducing acute toxicity |
| AUC | Total exposure over time | Often increased several-fold |
| t½ | Half-life | Extended from minutes–hours to hours–days |
| Vd | Volume of distribution | Reduced — carrier stays mainly in blood and MPS organs |
| CL | Clearance | Shifts from kidney/metabolism to liver and spleen uptake |
| F | Bioavailability | Raised for non-IV routes when the carrier protects the drug |
What controls nanoparticle biodistribution
| Factor | Effect |
|---|---|
| Size < 10 nm | Rapid renal clearance |
| Size 20–150 nm | Long circulation, possible tumour accumulation |
| Size > 200 nm | Fast capture by spleen and liver |
| Cationic surface | Protein binding, lung and liver uptake, toxicity |
| PEG coating | Longer circulation; anti-PEG antibodies can accelerate clearance on repeat dosing |
| ApoE adsorption | Drives LNP uptake into hepatocytes via LDL receptor |
Strengths
- Longer exposure. Carriers extend half-life and reduce dosing frequency.
- Lower toxicity. Reduced free-drug peaks protect heart, kidney and other organs.
- Payload protection. Nucleic acids and peptides survive enzymes in blood.
- Predictive modelling. PBPK models help translate animal data to human doses.
Challenges
- MPS dominance. Liver and spleen capture most of the injected dose.
- Complex bioanalysis. Separating encapsulated and released drug is technically demanding.
- Accelerated blood clearance. Repeat dosing of PEGylated carriers can trigger faster removal.
- Species differences. Rodent PK and EPR often overpredict human tumour exposure.
Where it is used
Dose selection
Exposure data set first-in-human doses and schedules.
Formulation ranking
Comparing carriers by AUC and organ distribution early.
Safety assessment
Identifying organs of accumulation for toxicology studies.
Regulatory filings
PK and biodistribution are core parts of IND and marketing applications.
What comes next
New tools let researchers see where every component of a nanomedicine goes, in real time and at single-cell resolution.
Barcoded nanoparticles
DNA barcodes test hundreds of formulations' biodistribution in one animal.
Whole-body imaging
PET and MRI track carriers and payloads non-invasively.
Single-cell readouts
Identifying exactly which cell types take up and express the cargo.
AI-driven PBPK
Models that predict human nanoparticle distribution from formulation properties.
A carrier changes where a drug goes and how long it stays — measuring and modelling that journey is what turns a promising formulation into a predictable medicine.