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Liposomes: Bubbles of Fat That Carry Drugs

The oldest and best-proven nanocarrier. See how a soap-like lipid spontaneously folds into a hollow sphere, why that lets it carry both watery and oily drugs, and how the same chemistry shows up in mRNA vaccines.

Why fat folds into a sphere

A liposome is built from phospholipids — molecules with a water-loving head and two water-hating fatty tails, the same dual nature that makes a surfactant work. Drop them in water and they cannot rest: the tails refuse contact with water while the heads crave it. The lowest-energy answer is a bilayer — two sheets of lipid tail-to-tail — that then closes on itself into a hollow ball, trapping a pocket of water inside.

Two pockets, two kinds of drug

The liposome's geometry gives it two storage spaces. A water-soluble drug dissolves in the trapped aqueous core. A fat-soluble drug tucks into the oily middle of the bilayer membrane. Which one you have decides where the drug rides — and how much you can load. The fraction that ends up inside, rather than left in the surrounding fluid, is the encapsulation efficiency, one of the first numbers any liposome formulator reports.

Encapsulation efficiency (EE%)

  EE% = (drug encapsulated / total drug added) × 100

Worked example — a doxorubicin liposome batch:
  Total drug added      = 50.0 mg
  Free drug measured
  in the outside fluid  =  4.0 mg
  Drug encapsulated     = 50.0 - 4.0 = 46.0 mg

  EE% = (46.0 / 50.0) × 100 = 92%

Reading it: 92% of the drug is inside the
liposomes; 8% is wasted in the medium and is
usually washed away before the final product.
Encapsulation efficiency: how much drug actually made it inside.

From lab curiosity to vaccine

Liposomes are the best-proven nanocarrier in the clinic: anticancer drugs like doxorubicin have been sold as liposomes for decades, partly because wrapping the drug spares the heart from its harshest effects. Close cousins broaden the toolkit — niosomes swap the natural phospholipid for a non-ionic surfactant, trading some authenticity for stability and lower cost.

The same lipid self-assembly underlies today's headline products. The mRNA vaccines do not use a classic hollow liposome but a denser lipid nanoparticle (LNP), yet the founding idea is identical: fragile genetic cargo, protected by a self-folding shell of fat. We return to LNPs in guide 5 of this track.