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  • Review Article
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Recent advances with liposomes as pharmaceutical carriers

Key Points

  • Liposomes — nano-sized phospholipid bubbles — have attracted much attention as potential drug carriers. Liposomes are easy to prepare, highly biocompatible and can be loaded with a broad variety of drugs, DNA and diagnostic agents. Their in vivo properties are easy to control. Many liposomal drugs are currently under development and some of them are already approved for clinical use.

  • Liposomes have been targeted to specific tissues by attaching specific ligands to their surface. Long-circulating liposomes have also been prepared by grafting the liposome surface with certain chemically and biologically inert synthetic polymers. Current liposomal preparation can combine longevity and targetability.

  • Various strategies have been developed to load liposomes with various biologically active substances including proteins (enzymes), peptides and DNA. Their in vivo properties, as well as their pharmacokinetics, have been investigated in many models. Drugs incorporated into liposomes do not provoke undesirable toxic or immune responses and are not inactivated by biological surroundings.

  • Currently used ligands for liposome targeting include antibodies and their fragments, folate, transferrin and certain peptides. Liposomes can be made stimuli-sensitive — that is, capable of releasing their contents at abnormal pH values and temperatures characteristic of pathological sites, such as cancers, in the body.

  • Liposomal drugs can be administered via different routes, including parenteral and oral administration, used in topical applications and can be delivered to the lungs using liposomal aerosols. Liposomes are also effective immunological adjuvants for protein and peptide antigens and are widely used in experimental immunology and for vaccine preparation.

  • New-generation liposomes have been proposed for the treatment of various diseases, including cancer. They are used as carriers of the agents used in photo-dynamic therapy, and the delivery of haemoglobin and bio-energic substrates. Liposomes are prepared possessing magnetic properties and ability to penetrate cell membranes and deliver their loads into cell cytoplasm.

Abstract

Liposomes — microscopic phospholipid bubbles with a bilayered membrane structure — have received a lot of attention during the past 30 years as pharmaceutical carriers of great potential. More recently, many new developments have been seen in the area of liposomal drugs — from clinically approved products to new experimental applications, with gene delivery and cancer therapy still being the principal areas of interest. For further successful development of this field, promising trends must be identified and exploited, albeit with a clear understanding of the limitations of these approaches.

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Figure 1: Evolution of liposomes.
Figure 2: Chemical reactions to attach various ligands (antibodies) to the liposome surface (all these reactions can be used to directly attach ligands to the liposome surface or to attach ligands to liposomes via the PEG spacer).
Figure 3: Liposome-cell interaction.
Figure 4: Fusogenic and stimuli-sensitive liposomes.
Figure 5: Liposomes in diagnostic imaging.
Figure 6: Cytoskeleton-specific immunoliposomes for drug and DNA delivery.

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DATABASES

Entrez Gene

Antennapedia

EGF

EGFR

HER2

interleukin-2

MUC1

SOD

tissue plasminogen activator

Tf

TfR

VIP

National Cancer Institute Cancer Topics

Acute myelogenous leukaemia

Glossary

RETICULO-ENDOTHELIAL SYSTEM

The physiological system responsible for the elimination of foreign macromolecules and particles from the body; macrophages of liver, spleen and lymphatic system play a key role in this elimination.

NUCLEOSOME

Subunit of chromatin (the complex of DNA plus specialized proteins — histones — in eukaryotic cells) composed of a short length of DNA wrapped around a core of histone proteins.

GANGLIOSIDES

Glycolipids with large size molecules; usually present on the outer surface of cell membranes.

PARENTERAL

Administered by means other than through the alimentary tract (such as intramuscular or intravenous injection).

IONTOPHORESIS

A means of enhancing the flux of ionic compounds across a membrane (such as the skin) by the application of an electric current across it.

ORAL TOLERANCE

The acquisition of a specific nonresponsiveness, via oral administration, to a molecule recognized by the immune system.

GAMMA-SCINTIGRAPHY

Medical diagnostic imaging modality based on the application of γ-emitting radioactive materials, such as 99m-Tc, 111-In, 125- and 131-I, 67-Ga, and some other isotopes with variable decay times.

RELAXIVITY

The property of certain metal ions to increase proton relaxation rate (relates to magnetic resonance imaging).

VIROSOMES

Liposomes with surface-attached or membrane-incorporated fragments of the viral protein coat.

HYPOVOLEMIC

A decrease in the volume of circulating blood.

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Torchilin, V. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4, 145–160 (2005). https://doi.org/10.1038/nrd1632

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