Development of a Nanocochleate based ApoA1 Formulation for the Treatment of Atherosclerosis and other Coronary Heart Diseases

Cochleate-delivery vehicles represent a new technology platform for oral and systemic delivery of drugs and are particularly applicable to macromolecules as well as small molecule drugs that are hydrophobic, charged or possess poor oral bioavailability.
Cochleates are derived from liposomes, which are suspended in aqueous two-phase polymer solutions, enabling the differential partitioning of polar molecules based-structure by phase separation. The liposome containing two-phase polymer-solution, treated with positively charged molecules such as Ca+2 or Zn+2, forms a cochleate precipitate of particle size less than 1 micron. They consist of alternating layers of phospholipids and multivalent cations existing as stacked sheets with little or no internal aqueous space. This unique structure provides protection from degradation for ‘’encochleated’’ drugs from digestive enzymes in the digestive tract. These nanocochleates containing drugs then can cross across the digestive epithelium and deliver drug molecules into target cells.
Atherosclerosis is a common disorder in which fatty substances, cholesterol, cellular wastes, and other substances progressively accumulate in the interior layers of arteries. This condition often progresses with advancing age and as it progresses can lead to heart failure, stroke, and other cardiovascular pathologies.
Hypercholesterolemia, a condition associated with high levels of low-density lipoproteins (LDL), and low levels of high-density lipoproteins (HDL), is universally accepted as a major risk factor for atherosclerosis and other cardiovascular diseases. The inverse relationship between HDLs and heart diseases is well documented. HDLs facilitate the cholesterol efflux from peripheral cells and, after enzyme-mediated cholesterol esterification, transports cholesteryl esters to the liver.
ApoA1 (a naturally existing lipoprotein) is an important HDL believed to be the most important in enzymatic esterification of cholesterol and then its transport to the liver, thus protecting the vessels against atherosclerosis.
Infusion or intraperitoneal administration of ApoA1 enhances the HDL ability to transport cholesterol to lever and protect against atherosclerosis but the major limitation for the use of ApoA1 as pharmacological/therapeutical agents has been the need for parenteral administration, as ApoA1 is a protein, it is rapidly degraded by GIT enzymes and so it is not delivered to blood as intact molecule.
So nanocochleates can provide a good platform for the delivery of ApoA1 by oral preparations and can bring a revolution in the treatment of atherosclerosis and other heart diseases originating from high blood cholesterol and LDL levels. I am interested to work in this field to assist the ailing people suffering from heart diseases.