Liposome

Source: Wikipedia, the free encyclopedia.
aqueous
solution.
Liposomes are composite structures made of phospholipids and may contain small amounts of other molecules. Though liposomes can vary in size from low micrometer range to tens of micrometers, unilamellar liposomes, as pictured here, are typically in the lower size range with various targeting ligands attached to their surface allowing for their surface-attachment and accumulation in pathological areas for treatment of disease.[1]

A liposome is a small artificial

DNA vaccines. Liposomes can be prepared by disrupting biological membranes (such as by sonication
).

Liposomes are most often composed of

egg and phosphatidylethanolamine, as long as they are compatible with lipid bilayer structure.[5] A liposome design may employ surface ligands for attaching to desired cells or tissues.[1]

Based on vesicle structure, there are seven main categories for liposomes: multilamellar large (MLV), oligolamellar (OLV), small unilamellar (SUV), medium-sized unilamellar (MUV), large unilamellar (LUV), giant unilamellar (GUV) and multivesicular vesicles (MVV).[6] The major types of liposomes are the multilamellar vesicle (MLV, with several lamellar phase lipid bilayers), the small unilamellar liposome vesicle (SUV, with one lipid bilayer), the large unilamellar vesicle (LUV), and the cochleate vesicle. A less desirable form is multivesicular liposomes in which one vesicle contains one or more smaller vesicles.

Seven main categories for liposomes: multilamellar large (MLV), oligolamellar (OLV), small unilamellar (SUV), medium-sized unilamellar (MUV), large unilamellar (LUV), giant unilamellar (GUV) and multivesicular vesicles (MVV))[7].

Liposomes should not be confused with lysosomes, or with micelles and reverse micelles.[8] In contrast to liposomes, micelles typically contain a monolayer of fatty acids or surfactants.[9]

Discovery

The word liposome derives from two Greek words: lipo ("fat") and soma ("body"); it is so named because its composition is primarily of phospholipid.

Liposomes were first described by British hematologist

plasmalemma was obvious, and the microscopic pictures provided the first evidence that the cell membrane is a bilayer lipid structure. The following year, Bangham, his colleague Malcolm Standish, and Gerald Weissmann, an American physician, established the integrity of this closed, bilayer structure and its ability to release its contents following detergent treatment (structure-linked latency).[13] During a Cambridge pub discussion with Bangham, Weissmann first named the structures "liposomes" after something which laboratory had been studying, the lysosome: a simple organelle whose structure-linked latency could be disrupted by detergents and streptolysins.[14] Liposomes are readily distinguishable from micelles and hexagonal lipid phases through negative staining transmission electron microscopy.[15]

Bangham, with colleagues Jeff Watkins and Standish, wrote the 1965 paper that effectively launched what would become the liposome "industry."Around that same time, Weissmann joined Bangham at the Babraham. Later, Weissmann, then an emeritus professor at New York University School of Medicine, recalled the two of them sitting in a Cambridge pub, reflecting on the role of lipid sheets in separating the cell interior from its exterior milieu. This insight, they felt, would be to cell function what the discovery of the double helix had been to genetics. As Bangham had been calling his lipid structures "multilamellar smectic mesophases," or sometimes "Banghasomes," Weissmann proposed the more user-friendly term liposome.[16][17]

Mechanism

A micrograph of phosphatidylcholine liposomes, which were stained with fluorochrome acridine orange. Method of fluorescence microscopy (1250-fold magnification).
Various types of phosphatidylcholine liposomes in suspension. Method of phase-contrast microscopy (1000-fold magnification). The following types of liposomes are visible: small monolamellar vesicles, large monolamellar vesicles, multilamellar vesicles, oligolamellar vesicles.

Encapsulation in liposomes

A liposome has an aqueous solution core surrounded by a

solutes dissolved in the core cannot readily pass through the bilayer. Hydrophobic chemicals associate with the bilayer. This property can be utilized to load liposomes with hydrophobic and/or hydrophilic molecules, a process known as encapsulation.[18] Typically, liposomes are prepared in a solution containing the compound to be trapped, which can either be an aqueous solution for encapsulating hydrophilic compounds like proteins,[19][20]
or solutions in organic solvents mixed with lipids for encapsulating hydrophobic molecules. Encapsulation techniques can be categorized into two types: passive, which relies on the stochastic trapping of molecules during liposome formation, and active, which relies on the presence of charged lipids or transmembrane ion gradients.[18] A crucial parameter to consider is the "encapsulation efficiency," which is defined as the amount of compound present in the liposome solution divided by the total initial amount of compound used during the preparation.[21] In more recent developments, the application of liposomes in single-molecule experiments has introduced the concept of "single entity encapsulation efficiency." This term refers to the probability of a specific liposome containing the required number of copies of the compound.[22]

Delivery

To deliver the molecules to a site of action, the lipid bilayer can fuse with other bilayers such as the

protons can pass through some membranes), the drug will also be neutralized, allowing it to freely pass through a membrane. These liposomes work to deliver drug by diffusion
rather than by direct cell fusion. However, the efficacy of this pH regulated passage depends on the physiochemical nature of the drug in question (e.g. pKa and having a basic or acid nature), which is very low for many drugs.

A similar approach can be exploited in the biodetoxification of drugs by injecting empty liposomes with a transmembrane pH gradient. In this case the vesicles act as sinks to scavenge the drug in the blood circulation and prevent its toxic effect.[25] Another strategy for liposome drug delivery is to target

digested while in the macrophage's phagosome, thus releasing its drug. Liposomes can also be decorated with opsonins and ligands
to activate endocytosis in other cell types.

Certain anticancer drugs such as doxorubicin (Doxil) and daunorubicin may be administered encapsulated in liposomes. Liposomal cisplatin has received orphan drug designation for pancreatic cancer from EMEA.[26]

The use of liposomes for transformation or

lipofection
.

In addition to gene and drug delivery applications, liposomes can be used as carriers for the delivery of dyes to textiles,[27] pesticides to plants, enzymes and nutritional supplements to foods, and cosmetics to the skin.[28]

Liposomes are also used as outer shells of some microbubble contrast agents used in contrast-enhanced ultrasound.


Dietary and nutritional supplements

Until recently, the clinical uses of liposomes were for

gastric system and small intestines allowing the encapsulated nutrient to be efficiently delivered to the cells and tissues.[31]

The term nutraceutical combines the words nutrient and pharmaceutical, originally coined by Stephen DeFelice, who defined nutraceuticals as “food or part of a food that provides medical or health benefits, including the prevention and/or treatment of a disease”.[32] However, currently, there is no conclusive definition of nutraceuticals yet, to distinguish them from other food‐derived categories, such as food (dietary) supplements, herbal products, pre‐ and probiotics, functional foods, and fortified foods.[33] Generally, this term is used to describe any product derived from food sources which is expected to provide health benefits additionally to the nutritional value of daily food. A wide range of nutrients or other substances with nutritional or physiological effects (EU Directive 2002/46/EC) might be present in these products, including vitamins, minerals, amino acids, essential fatty acids, fibres and various plants and herbal extracts. Liposomal nutraceuticals contain bioactive compounds with health-promoting effects. The encapsulation of bioactive compounds in liposomes is attractive as liposomes have been shown to be able to overcome serious hurdles bioactives would otherwise encounter in the gastrointestinal (GI) tract upon oral intake.[34]

It is important to note that certain factors have far-reaching effects on the percentage of liposome that are yielded in manufacturing, as well as the actual amount of realized liposome entrapment and the actual quality and long-term stability of the liposomes themselves.[35] They are the following: (1) The actual manufacturing method and preparation of the liposomes themselves; (2) The constitution, quality, and type of raw phospholipid used in the formulation and manufacturing of the liposomes; (3) The ability to create homogeneous liposome particle sizes that are stable and hold their encapsulated payload. These are the primary elements in developing effective liposome carriers for use in dietary and nutritional supplements.

Manufacturing

The choice of liposome preparation method depends, i.a., on the following parameters:[36][37]

  1. the physicochemical characteristics of the material to be entrapped and those of the liposomal ingredients;
  2. the nature of the medium in which the lipid vesicles are dispersed
  3. the effective concentration of the entrapped substance and its potential toxicity;
  4. additional processes involved during application/delivery of the vesicles;
  5. optimum size, polydispersity and shelf-life of the vesicles for the intended application; and,
  6. batch-to-batch reproducibility and possibility of large-scale production of safe and efficient liposomal products

Useful liposomes rarely form spontaneously. They typically form after supplying enough energy to a dispersion of (phospho)lipids in a polar solvent, such as water, to break down multilamellar aggregates into oligo- or unilamellar bilayer vesicles.[5][24]

Liposomes can hence be created by

phospholipids, in water.[8] Low shear rates create multilamellar liposomes. The original aggregates, which have many layers like an onion, thereby form progressively smaller and finally unilamellar liposomes (which are often unstable, owing to their small size and the sonication-created defects). Sonication is generally considered a "gross" method of preparation as it can damage the structure of the drug to be encapsulated. Newer methods such as extrusion, micromixing[38][39][40] and Mozafari method[41] are employed to produce materials for human use. Using lipids other than phosphatidylcholine can greatly facilitate liposome preparation.[5]

Prospect

Pictorial representation of targeted theranostics liposomal delivery

Further advances in liposome research have been able to allow liposomes to avoid detection by the body's immune system, specifically, the cells of

transfersomes.[47]

Liposomes are used as models for artificial cells.

Liposomes can be used on their own or in combination with traditional antibiotics as neutralizing agents of bacterial toxins. Many bacterial toxins evolved to target specific lipids of the host cells membrane and can be baited and neutralized by liposomes containing those specific lipid targets.[48]

A study published in May 2018 also explored the potential use of liposomes as "nano-carriers" of fertilizing nutrients to treat malnourished or sickly plants. Results showed that these synthetic particles "soak into plant leaves more easily than naked nutrients", further validating the utilization of nanotechnology to increase crop yields.[49][50]

leuprolide acetate loaded liposomes[52]
and to predict the particle size and the
polydispersity index of liposomes.[53]

See also

References

  1. ^
    S2CID 9464592
    .
  2. ^ .
  3. ^ "Cell Membranes - Kimball's Biology Pages". 16 August 2002. Archived from the original on 25 January 2009.
  4. ^ Mashaghi S., et al. Lipid Nanotechnology. Int J Mol Sci. 2013 Feb; 14(2): 4242–4282.
  5. ^
    PMID 22266051
    .
  6. .
  7. .
  8. ^ a b Stryer S. (1981) Biochemistry, 213
  9. ^ Mashaghi S., et al. Lipid Nanotechnology. Int J Mol Sci. 2013 Feb; 14(2): 4242–4282.
  10. PMID 14187392
    .
  11. .
  12. .
  13. .
  14. .
  15. .
  16. .
  17. . Retrieved 2014-10-01.
  18. ^ .
  19. .
  20. .
  21. .
  22. .
  23. .
  24. ^ a b Barenholz, Y; G, Cevc (2000). Physical chemistry of biological surfaces, Chapter 7: Structure and properties of membranes. New York: Marcel Dekker. pp. 171–241.
  25. PMID 21067150
    .
  26. ^ Anonymous (2018-09-17). "EU/3/07/451". European Medicines Agency. Retrieved 2020-01-10.
  27. S2CID 137500401
    .
  28. .
  29. ^ Yoko Shojia; Hideki Nakashima (2004). "Nutraceutics and Delivery Systems". Journal of Drug Targeting.
  30. PMID 15640487
    .
  31. .
  32. .
  33. .
  34. .
  35. .
  36. .
  37. .
  38. .
  39. .
  40. .
  41. .
  42. .
  43. .
  44. .
  45. .
  46. .
  47. .
  48. ..
  49. .
  50. ^ Temming, Maria (2018-05-17). "Nanoparticles could help rescue malnourished crops". Science News. Retrieved 2018-05-18.
  51. PMID 33615570
    .
  52. .
  53. .

External links