Nanoparticles formed from materials as diverse as titanium dioxide and phospholipids are highly attractive to biomedical engineers as vehicles to deliver a variety of cosmetics, drugs, and diagnostic materials to targeted sites in the human body. Nanoparticles employed in the pharmaceutical industry are typically formed from elongated biomolecules, such as phospholipids, having one hydrophilic end and one hydrophobic end. Molecules having the latter properties are known as amphiphilic (also called amphipathic) molecules or amphiphiles. Phospholipids are typical amphiphiles with phosphatidylcholine being the favored phospholipid used to form biological nanoparticles. Phospholipid-based nanoparticles are particularly attractive as in vivo drug/diagnostic delivery devices since they are formed from nontoxic substances normally found in cells and cell membranes. Nanoparticles bioengineered from customized combinations of phospholipids with one or two fatty acid substituents, cholesterol, and other polyols are known as micelles, vesicles, or liposomes depending upon the geometry of the structure formed. Micelles are small spherical aggregates typically formed from phospholipids having one fatty acid substituent. In micelles the interior of the sphere is packed with the hydrophobic hydrocarbon chain of the fatty acid with the charged or polar end of the phospholipid exposed to the polar, aqueous environment. The hydrophobic interior allows micelles to be stably loaded with water insoluble, and/or toxic drugs, or diagnostics and injected into the blood stream where they circulate and potentially deliver the carried compounds to target sites in the body. However, due to their small size, micelles have a limited loading capacity and most lipid-based nanoparticulate delivery devices have focused on the use of vesicles or liposomes. Liposomes and vesicles are typically formed from phospholipids plus cholesterol with the phospholipid, usually phosphatidylcholine, containing two fatty acid substituents. Like micelles, liposomes and vesicles form spontaneously when the mixed lipid formulations are dispersed in a polar solvent, such as water, with the lipid formulation and method of dispersion determining the geometry of the resultant particles. Although the nomenclature is not consistent, spherical particles with the phospholipids oriented into a single welldefined bilayer membrane, much like the biological membrane illustrated in figure, are generally referred to as liposomes while particles of ambiguous shape and form are generally referred to as vesicles. The key attributes of liposomes or vesicles are that they are formed of spherically closed bilayer membranes, with the hydrophobic acyl chains of phospholipids from the two sides of the membrane oriented to the inside of the bilayer and the polar portion of the phospholipids oriented toward the aqueous/polar environments on the exterior and interior of the nanoparticles. The figure below illustrates one hemisphere of a spherical, hollow, unilamellar-membrane liposome In pharmaceutical applications, customized lipid formulations are dispersed in aqueous solutions containing a drug or diagnostic compound and liposome formation proceeds with the interior aqueous compartment trapping a few nanoliters of drug solution ready to be injected into the blood stream or other body site. Early researchers using liposome-encapsulated anticancer drugs found that higher drug levels could be delivered to solid tumors but that most of the liposomes were removed from the circulatory system by reticuloendothelial system (RES) cells (e.g., phagocytic macrophages and liver Kupffer cells). Subsequently, “stealth liposomes” cloaked or coated with compounds like polyethylene glycol have been shown to be capable of largely avoiding destruction by the RES. At the same time, animal studies have shown that by bonding targeting molecules, like immunoproteins against cell surface markers, to the liposome surface, tissue-specific targeting can be markedly improved. In the near future many new, targeted, liposome/drug formulations can be expected to appear in clinical medicine and other industries as diverse as cosmetics and nutraceuticals.
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