What are
Liposomes are closed vesicular structures that can range from 20-25 nm up to 2.5 μm (or 2500 nm). Their structure (very similar to that of cell membranes) is characterized by the presence of one or more double layers of amphiphilic lipids that delimit a hydrophilic core in which material is found in aqueous phase. Furthermore, the aqueous phase is also present outside the liposomes.
The interest in this discovery was immediately high, especially in the medical-pharmaceutical field. Not surprisingly, since the 1970s liposomes have been used, in experimental form, as drug vehicles. Little by little, researchers have learned to perfect the characteristics of liposomes, so as to make them able to exert the sought therapeutic effect.
Research in this area has been and still is very intense, so it is not surprising that liposomes are currently used as effective Drug Delivery systems.
Structure
Structure and Properties of Liposomes
As mentioned, liposomes have a structure that is characterized by the presence of one or more double layers of amphiphilic lipids. In detail, these double layers are mostly formed by phospholipid molecules: those of the outermost layer are regularly placed side by side and expose their polar head (hydrophilic portion of the molecule) towards the watery environment that surrounds them; the apolar tail (hydrophobic portion of the molecule) is instead turned towards the inside, where it is intertwined with that of the second lipidic layer, which has an organization mirroring the previous one. In fact, in the internal phospholipid layer, the polar heads face the aqueous environment contained in the liposome cavity.
Thanks to this particular structure, the liposomes can remain immersed in an aqueous phase while simultaneously housing an aqueous content inside them in which active principles or other molecules can be dispersed.
At the same time - thanks to the double phospholipid layer - the entry and exit of water molecules or of polar molecules is prevented, effectively isolating the content of the liposome (which cannot be modified by entry or exit) of water or polar solutes).
niosomes
Niosomes ( Non Ionic Liposomes ) are special liposomes whose structure is different from the "classic" liposomes. In fact, in niosomes the phospholipid layers are replaced by non-ionic amphiphilic synthesis lipids, usually added to cholesterol. The niosomes are smaller than 200 nanometers, they are very stable and have various peculiar characteristics which - among other things - make them very suitable for topical use.
Features
The characteristics of liposomes depend on the typical structure of which these vesicles are equipped. The outer layers, in fact, possess a remarkable affinity for the plasmatic membranes, of which they outline in broad terms the composition (natural phospholipids like phosphatidylcholine, phosphatidylethanolamine and cholesterol esters).
In this way, the water-soluble substances contained within the liposomal microspheres can be easily conveyed inside the cells.
At the same time, the liposome can also incorporate pharmacologically active lipophilic molecules into its external phospholipid bilayer.
Moreover, as mentioned, the characteristics of liposomes can be improved in order to adapt the vesicles to the most varied requirements. To do this, it is necessary to intervene by making structural changes of various kinds depending on the objective to be achieved: for example, the problem relating to the instability of phospholipids (high tendency to oxidation), can be solved by partial hydrogenation, addition of an antioxidant (alpha-tocopherol) or by resorting to lyophilization (proliposomes), which allows preserving the stability of the vesicles for very long times.
Furthermore, the lipid bilayer can be constructed so as to increase the binding to certain cell types, for example through antibodies, lipids or carbohydrates. In the same way, the affinity of the liposomes for a given tissue can be modified by varying the composition and the electric charge (by adding stearylamine or phosphatidylserine vesicles with positive charge are obtained, while with dicetyl phosphate, negative charges are obtained), which increases the concentration of the drug in the target organ.
Finally, to increase the half-life of liposomes it is possible to modify the surface by conjugating polyethylene glycol molecules (PEG) to the lipid bilayer, producing the so-called " Stealth Liposomes ". An FDA-approved cancer drug treatment uses PEG-coated liposomes that transport doxorubicin. As stated above, this coating significantly increases the half-life of liposomes, which gradually concentrate in cancer cells permeating the capillaries of the tumor; these, in fact, being of recent formation, are more permeable than those of healthy tissues, and as such allow the liposomes to accumulate in the neoplastic tissue and release here the active principles toxic for the cancer cells.
uses
Uses and Applications of Liposomes
Thanks to their particular characteristics and structures, liposomes are used in various fields: from the medical and pharmaceutical fields to the purely cosmetic one. In fact, since the liposomes have a high affinity for the stratum corneum, they are intensively used in this area to favor the cutaneous absorption of functional substances.
As far as the medical and pharmaceutical field is concerned, instead, liposomes find applications both in the therapeutic and diagnostic fields.
In particular, the ability of liposomes to isolate their contents from the external environment is particularly useful in the conveyance of substances prone to degradation (such as, for example, proteins and nucleic acids).
At the same time, liposomes can be exploited to reduce the toxicity of some drugs: this is the case, for example, of doxorubicin - an anticancer drug that is indicated in ovarian and prostate cancer - which is encapsulated in long-circulation liposomes has seen its pharmacokinetics considerably modified, as well as improved the degree of efficacy and toxicity.
Classification
Classification and Types of Liposomes
The classification of liposomes can be carried out according to different criteria, such as: dimensions, structure (number of double lipid layers of which the liposome is composed) and preparation method adopted (this last classification, however, will not be taken into consideration in the article course).
These classifications and the main types of liposomes will be briefly described below.
Classification based on structural and dimensional criteria
Depending on the structure and number of phospholipid double layers each vesicle is equipped with, it is possible to divide the liposomes into:
Unilamellar liposomes
Unilamellar liposomes consist of a single phospholipid bilayer that encloses a hydrophilic core.
Depending on their size, unilamellar liposomes can be further classified into:
- Small unilamellar vesicles or SUVs ( Small Unilamellar Vesicles ) whose diameter can vary from 20 nm to 100 nm;
- Large unilamellar vesicles or LUV ( Large Unilamellar Vesicles ) whose diameter can vary from 100 nm up to 1 μm;
- Giant unilamellar vesicles or GUV ( Giants Unilamellar Vesicles ) whose diameter is greater than 1 μm.
Multilamellar liposomes
The multilamellar liposomes or MLV ( MultiLamellar Vesicles ) are more complex, because they are characterized by the concentric presence of various lipid layers (generally more than five), separated from each other by aqueous phases (onion skin structure). For this particular feature, multilamellar liposomes reach diameters ranging from 500 to 10, 000 nm. With this technique it is possible to encapsulate a higher number of lipophilic and hydrophilic active principles.
Also belonging to the group of multilamellar liposomes are the so-called oligolamellos or OLV ( OligoLamellar Vesicles ) liposomes, always consisting of a series of concentric double phospholipid layers, but of a lower number compared to the "proper" multilamellar liposomes.
Multivescicular liposomes
The multivescicular liposomes or MVV ( MultiVesicular Vesicles ) are characterized by the presence of a double phospholipid layer inside which other liposomes are enclosed which, however, are not concentric as in the case of multilamellar liposomes.
Other classifications
In addition to what has been seen so far, it is possible to adopt another classification system that divides liposomes into:
- PH sensitive liposomes : they are vesicles that release their contents in slightly acid environments. In fact, at pH 6.5 the lipids that constitute them protonate and favor the release of the drug. This characteristic is useful because very often at the level of tumor masses there is a significant lowering of the pH, due to the necrotic tissue that is forming with the growth of the tumor.
- Temperature-sensitive liposomes : they release their contents at a critical temperature (generally around 38-39 ° C). To this end, after the administration of the liposomes, the area where the tumor mass is present is heated, for example by ultrasound.
- Immunoliposomes : they release their content when they come into contact with a cell that has a specific antigen.
Advantages and disadvantages
Main advantages and disadvantages of liposomes
The use of liposomes has a number of considerable advantages, such as:
- The constituents of the external phospholipid layers are biocompatible, so they do not cause unwanted toxic or allergic effects;
- I am able to incorporate both hydrophilic and lipophilic molecules in the target tissues;
- The substances conveyed are protected by the action of enzymes (proteases, nucleases) or by denaturing environments (pH);
- They are able to reduce the toxicity of toxic or irritating agents;
- They can be administered through different routes (oral, parenteral, topical, etc.);
- They can be synthesized in such a way as to increase their affinity for particular target sites (proteins, tissues, cells, etc.);
- They are biodegradable, free of toxicity and can currently be prepared on a large scale.
