The Application of Cholesterol in Liposomes

When mentioning cholesterol (HP), people always associate it with diseases like high blood fat, high blood pressure, and arteriosclerosis, and are fearful of cholesterol (HP). Did you know? Actually, cholesterol is one of the essential nutrients for the human body. Cholesterol (HP) is an important substance for synthesizing bile acids, and the digestive capability of bile mainly relies on bile acids; moreover, cholesterol is an essential component of cell membranes and a precursor for synthesizing various hormones. Therefore, if you excessively avoid foods containing cholesterol, it can easily cause nutritional imbalance, leading to anemia and other illnesses. Next, let's take a look at the role of cholesterol in liposomes.

Medicinal Uses of Cholesterol

Many hormones used in clinical practice are synthesized using cholesterol (HP). Additionally, cholesterol is an additive in some advanced drug carriers. Cholesterol (HP) can regulate the fluidity of the phospholipid bilayer membrane, reducing membrane permeability and minimizing drug leakage. It also helps maintain a certain level of flexibility in the lipid membrane, enhancing the ability of liposome vesicles to withstand external environmental changes and offers some protection against phospholipid oxidation.

In the preparation of conventional drug-loaded liposomes, cholesterol (HP) is a necessary additive. Depending on the types of PC and drugs, there is an optimal amount of cholesterol (HP) that should be used. Within a certain range, the particle size, oxidative stability, and physical stability of liposomes are positively correlated with the amount of cholesterol (HP) added. Exceeding this range, surpassing the membrane load, can cause some liposomes to rupture.

Moreover, the addition of cholesterol (HP) can affect the phase transition temperature of the membrane. Within the critical value, it lowers the phase transition temperature, while exceeding the critical value raises the phase transition temperature. Thermosensitive liposomes have special kinetic characteristics; to reduce stability during the phase transition temperature and to release drugs quickly, cholesterol (HP) may not be added.

Methods of Extracting Medicinal Cholesterol

The demand for medicinal cholesterol (HP) is quite high every year. As cholesterol (HP) is a multi-chiral substance, it is difficult to synthesize. Currently, it is still obtained via extraction from animal tissues and lanolin.

Extraction from animal tissues

The extraction method from animal tissues uses fresh animal organs, bone marrow, and brain as raw materials. The process involves acetone extraction → ethanol refinement → sulfuric acid hydrolysis → low-temperature crystallization → activated carbon decolorization → multiple crystallizations. This process is simple and feasible and is currently the main production process for cholesterol (HP). However, it is easily restricted by the supply of raw materials and carries the risk of product contamination with pathogenic genes.

Extraction from lanolin

Lanolin is a byproduct of the wool industry, with a relatively high cholesterol (HP) content, about 10~15%. It is inexpensive, abundantly available, and offers high stability and safety. Most cholesterol (HP) abroad is derived from lanolin. However, in lanolin, cholesterol (HP) is mostly bound with lanolin fatty acids in ester form, and there are many cholesterol (HP) analogs, requiring high technical standards to obtain pure products. The saponification process is used to release free cholesterol (HP) from lanolin. The cholesterol (HP) obtained via saponification still contains a large amount of dehydrocholesterol, dihydrocholesterol, and other analogs. As their molecular structures and properties are similar, separation is challenging, posing as the key difficulty in the process. Nonetheless, with increasing attention to drug safety, cholesterol (HP) derived from lanolin is bound to gradually replace cholesterol (HP) sourced from animal viscera.