How does nanoparticle drug delivery work?

Last updated: October 2026

Nanoparticle drug delivery packs a drug into a carrier roughly 1 to 100 nanometers across, built from lipids, polymers or inorganic materials. The carrier protects fragile cargo, changes where the drug goes in the body and helps it enter cells. Lipid nanoparticles carry the mRNA in COVID-19 vaccines, yet across published tumor studies a median of only 0.7% of the administered dose reached the tumor.

What counts as a nanoparticle in drug delivery?

Nanomaterials are commonly defined as materials with sizes between 1 and 100 nanometers⁴. In drug delivery, the particles fall into three broad families: lipid-based, polymeric and inorganic nanoparticles¹. As each family is engineered in more specific ways, particles can be optimized for delivery in a more personalized manner, the basis of precision nanomedicine¹.

FDA guidance describes nanomaterials in drug products serving as active ingredients or as inactive ingredients, including carriers loaded with an active ingredient⁵. Because such materials can give a product attributes that differ from those of conventional products, FDA says they may merit particular examination during development⁵.

How does a nanoparticle carry a drug to where it is needed?

Once in the bloodstream, a particle's fate depends on its size, shape, charge and coating¹. Many formulations add polyethylene glycol (PEG) as a stealth coating, which lengthens circulation time by shielding the surface from enzymes and antibodies, although it does not completely prevent recognition by immune cells¹. Particles still distribute across organs in a size-dependent way, with the highest accumulation often in the liver and spleen¹.

In tumors, abnormal, leaky blood vessels can let particles out of circulation, a phenomenon called the enhanced permeation and retention (EPR) effect¹. Particles can also carry targeting ligands that bind markers on diseased cells, although active targeting is not yet an ideal solution¹.

Getting into the right cell is only half the job; the cargo must then escape. Ionizable lipids in LNPs are neutral at physiological pH but become positively charged inside the acidic endosome, which may destabilize its membrane and release the cargo into the cell². For oral delivery, the gut is a tougher barrier: enterocytes preferentially absorb particles of 20 to 100 nanometers and M cells particles of 100 to 500 nanometers, and passive diffusion across the gut wall remains limited¹.

What is the difference between a liposome and a nanoparticle?

A liposome is one kind of nanoparticle. Liposomes are phospholipid vesicles with one or more concentric lipid bilayers enclosing a water core, so they can carry water-loving drugs inside and fat-loving drugs within the bilayer³. They are the largest subset of lipid-based nanoparticles, and lipid-based particles are the most common class of FDA-approved nanomedicines¹.

Lipid nanoparticles, the carriers used for nucleic acids, are liposome-like but differ mainly because they form micellar structures within the particle core¹. In LNP and mRNA formulations made by rapid mixing, the mRNA is held in that interior core through electrostatic interactions with the lipids².

Size ranges overlap. Liposomes are usually 50 to 450 nanometers across, so many are larger than the 1 to 100 nanometer range often used to define nanomaterials⁴.

Which nanoparticle medicines are already approved?

FDA-approved nanomedicines date back to the early 1990s: the iron product INFeD was approved in 1992 and the liposomal product Doxil in 1995, and approved nanomedicines now span lipid-based, polymer-based and inorganic products used for cancer, fungal infections, iron deficiency and multiple sclerosis, among other conditions¹.

Lipid nanoparticles reached the mainstream with nucleic acids. Onpattro (patisiran), a lipid nanoparticle carrying siRNA, was the first FDA-approved siRNA drug, and its ionizable lipid DLin-MC3-DMA is a key component². Two COVID-19 vaccines, mRNA-1273 and BNT162b, use lipid nanoparticles to deliver antigen mRNA, with SM-102 and ALC-0315 as their respective ionizable lipids².

Approval has not always meant a large clinical gain. Of the nanomedicines that are approved, few are recommended as first-line treatments, and many improve outcomes in only a small subset of patients¹.

Why do so few nanoparticles reach their target?

A survey of ten years of literature found that a median of only 0.7% of the administered nanoparticle dose is delivered to a solid tumor⁶. That analysis covered 232 data sets, and its result greatly de-emphasized the role of the EPR effect¹. The authors of the survey point to competing organs, the mononuclear phagocytic and renal systems, as well as tumor biology⁶.

Other barriers compound the problem. The EPR effect varies with patient factors such as age, genetics, lifestyle and previous treatment¹. Antibodies against PEG, formed after earlier exposure, can undo the stealth coating and promote clearance¹. LNP systems can be limited by low drug loading and high uptake by the liver and spleen¹.

The 2021 review concludes that smarter particle designs are still needed to improve cargo delivery, and that a patient's own tumor and vasculature should inform the choice of platform¹.