Liposomes
Liposomes
• Liposomes were first described by Alec Bangham following his observations that phospholipids in aqueous systems can form closed bilayered
structures (Bangham and Horne 1964). Since then, liposomes have moved a long way from being just an fundamental object of biophysical research to become a pharmaceutical carrier of choice for numerous practical
applications (Torchilin 2006). For many years, liposomes have been
commonly used as delivery vehicles for drugs, vaccines, genes or cosmetics (Allen 1998; Gregoriadis 1988; Hart 2005).
• Liposome Structure
• Liposomes are spherical (Figure 3), self-closed structures formed by one or several concentric lipid bilayers with an aqueous phase inside and between the lipid bilayers (Torchilin 2006). They can accommodate the water-
soluble (hydrophilic) material in the inner aqueous core and the lipophilic material in the bilayer region (Allen 1998).
• The success of liposomes as delivery systems has been reported in a number of preclinical and clinical trials (Al- Jamal and Kostarelos 2011; Malam et al. 2009; Thierry 2009).
• Clinicians have been used liposomes as nanoscale system to deliver encapsulated anthracycline molecules for cancer therapy.
• Many research efforts have been directed towards improving the safety profile of these drugs such as
doxorubicin and daunorubicin, along with vincristine, which
are associated with severe cardiotoxic side effects, as well
as acute gastrointestinal and other toxicities (Al-Jamal and
Kostarelos 2011).
Advantages
• Liposomal entrapment of these drugs showed reduced cardiotoxicity, dermal toxicity and better survival of
experimental animals compared to the controls receiving free drugs. Encouraging results have been obtained from early
clinical applications and clinical trials of different liposomal drugs (Chang 2012; Thierry 2009). Many more liposomal-
based drug formulations with improved blood circulation and therapeutic efficacy are still under investigation in preclinical studies for the delivery of small molecules recombinant
proteins, antisense oligonucleotides and cloned genes (Al-
Jamal and Kostarelos 2011; Chang 2012).
Structure of liposomes
• The chemical composition of the liposome determines properties such as membrane fluidity, surface charge, density and permeability. In addition to these properties, liposomes can be characterized by size and shape.
• There are different types of liposomal vesicle:
• Multilamellar vesicles (MLVs): range in size from 500 to 5,000 nm and consist of several concentric bilayers
• Small unilamellar vesicles (SUVs): around 100 nm in size and formed by a single bilayer
• Large unilamellar vesicles (LUVs): range in size from 200 to 800 nm
• Size and lamellarity are generally controlled by the preparation method of the liposomes (Torchilin and Weissig 2003; Torchilin 2006) (Torchillin 2003 and 2005).
• Liposomal formulation can be further improved by incorporating steric protectors (such as polyethylene glycol) in order to achieve long-circulating liposomes or by attaching antibodies to the surface of the liposome in order to increase the accumulation in the desired tissue or organ.
• Liposomes can function as sustained release systems for drugs and the rate of release can be manipulated (Allen 1998). Four different
mechanisms play role in the liposome-cell interaction by which liposomes can deliver their contents to cells. Adsorption of the
liposome followed by extracellular release of the contents results in subsequent active or passive transport of these contents into the cells (Torchilin and Weissig 2003). Adsorption can also be followed by
selective transfer of lipophilic compounds from the lipid bilayer to the plasma membrane (Pagano and Weinstein 1978). Endocytosis, another mechanism, may lead to internalization of the liposomes followed by intracellular release of the contents (Düzgüneş and Nir 1999). Lastly, fusion of the liposomal membrane with the plasma membrane or the intracellular endosomal membrane releases the liposomal contents in the cytoplasm (Torchilin and Weissig 2003). The liposome
characteristics, as well as the cellular and environmental factors
determine the type of mechanism involved in liposome-cell interaction.
