Generally speaking, though, phagocytes are bad news for liposomes, which they usually dispatchwithin minutes of administration.
Camouflaging the liposomes so as to fool phagocytes intoignoring them thus became a key objective of pharmaceutical chemists during the 1970s and beyond. (Liposomes were discovered in England in 1965.
) The result of their efforts was a process called
in which countless molecules of a synthetic, nontoxic polymer, polyethylene glycol (PEG), are attached, at one end of the polymer chain, to the surface of theliposome.
The long, slender, highly flexible PEG molecules slosh around the liposome likespaghetti boiling in a pot. Because of their chemical affinity for water molecules, they areheavily hydrated. To phagocytes, this molecular “cloak” of water of hydration makes thePEGylated liposomes look like little watery blobs rather than something edible, so they tend toleave them alone. Mission accomplished!The two main advantages of PEGylated liposomes for delivering drugs or supplements are
and the possibility, in some cases, of
to the organs or tissues that most need them.
Let’s look at these two benefits in turn.
Types Of LIPOSOMES
:There are four basic kinds of liposomes, each with its own advantages and disadvantages. All of them consist of a spherical cell membrane (lipid bilayer) that encapsulates a payload of therapeutic molecules. All of them bypass the digestive tract, thus increasing the bioavailabilityof their payloads, which remain biologically inert until the cell membrane ruptures. When andwhere that occurs, and why and how it occurs, is what makes the difference. It depends on manydifferent physical and chemical properties of the liposomes and on the physiological environmentin which they find themselves.
are “naked,” i.e., they’re ordinary liposomes made from simple phospholipids, with nothing to protect them from phagocytes. Their surfaces (both exterior andinterior) are either electrically neutral or negatively charged (depending on the specific nature of the lipid molecules used in making the bilayer. These liposomes are used mainly to deliver drugsto the phagocytes that eat them, so as to treat disorders of the phagocytes themselves or to treatdiseases of the liver or spleen, where most phagocytes are found. The latter form of treatment ismade possible by drugs that are re-released unharmed by the phagocytes.
are “stealth” liposomes that evade detection and destruction by phagocytes by virtue of their cloaks of hydrated PEG (polyethylene glycol) molecules. Their purpose is two-fold: (1) to increase the bioavailability of drugs or supplements by bypassing the digestive tract,and (2) to minimize any potential toxicity or side effects of these agents by remaining in thecirculation for a long time and releasing their payloads slowly. As a bonus, they’re passivelytargeted to tumors and to inflamed tissues, where they’re preferentially absorbed because of theincreased permeability of the capillaries that nourish these tissues.
are stealth liposomes that have been specially designed for active targeting toa given type of tissue or organ that the liposome is able to recognize by its molecular fingerprint.This is accomplished by highly specific chemical modifications to the PEG molecules or the lipid