Liposomes - Introduction
Today liposomes are an important part of biological, pharmaceutical, and medical research. Because liposomes are the most effective carriers for the introduction of many different types of agents into cells, the applications of liposome-based samples and products are as follows: extremely wide. A few examples are:
Liposomes are used for studying protein-liposome interactions with compounds such as serum lipoproteins, lectins, toxins and clotting components.
They are used for the entrapment of anti-tumor agents, anti-microbial drugs, anti-inflammatory and immunomodulatory agents and CNS-active drugs. The therapeutic applications are presently include cancer therapy, arthritis, metal chelation therapy, enzyme replacement therapy, hemophilia (factor VIII), myocardial infarction, and as radiopharmaceutical markers.
Liposomes are used for studying in vitro and in vivo liposome-cell interactions.
They are used for reconstitution experiments especially for ion transport systems.
In molecular biology, liposomes are used for the mediated delivery of macromolecules into eukaryotic cells.
In immunology, antigens encapsulated in liposomes are used to generate antibodies, to mediate active and passive immunization and for many other applications.
The use of liposomes in gene-based technology and in broader biotechnology and pharmaceutical applications is increasing day by day.
Harvard Apparatus offers two instruments, the Mini Lipoprep and the Liposomat, for fast, easy and reproducible liposome preparation. No prior experience in liposome preparation is necessary.
Using these systems, liposomes can be prepared with virtually any lipid, depending on the specifications of the experiment and the types of biomolecules that need to be encapsulated. Liposome preparation with these instruments is highly reproducible and compared to other liposome preparation methods on the market, these liposomes are very stable. Under sterile conditions, liposomes prepared using the Mini Lipoprep and Liposomat can be stored for one year or longer.
Details of these instruments are on the next page.
With a few exceptions, liposomes are composed of natural or synthetic phospholipids, mostly lecithins. Hence, they can be metabolized in vivo and are generally non-toxic and non-antigenic.
Agents can be entrapped in liposomes without the formation of chemical bonds and sensitive molecules can be protected within them. Because of their restricted permeability, liposomal preparations offer a controllable, time-dependent release system.
The entrapment of a drug within liposomes changes its pharmaco-kinetics and can result in a better therapeutic index and enhanced cellular uptake. Since different agents need different lipid agents to create an optimal coat, in vivo experiments following liposome preparation are often the optimal means of determining which lipid represents the best compromise between permeability and in vivo stability for any given agent.
Stability of Liposomes
No general rule for maintaining liposome stability exists since it depends on several parameters, such as the type of lipid used, the properties of the drug/agent in the liposomes, their size, lamellarity, and homogeneity, the electrolyte content and pH of the medium used, and also on the specifications of the desired application.
The size of liposomes can be adjusted experimentally by varying several parameters: the dialysis rate, type of detergent, type of lipid(s), lipid/detergent molar ratio, lipid concentration, electrolyte content and pH.
The detergents used are gentle in their action and are not expected to hydrolyze or peroxidize liposome components. The most frequently used detergents are sodium cholate, n-octyl-b-Dglucopyranoside and n-octyl-tetraoxyethylene (POE4). Other detergents are sodium salts of glycocholic acid, deoxycholic acid, taurocholic acid, chenoxycholic acid, n-hexyl- and n-heptylglucopyranoside and lauryldimethylamine oxide.
For details of liposome preparation instruments, please see the next page.