Surface modification of liposomes

Torchilin VP, Weissig V, Martin FJ, Heath TD, New RRC. Surface modification of liposomes. In Torchilin VP, Weissig V, eds. Liposomes A Practical Approach. Oxford, U.K. Oxford University Press, 2003 193. 

Although liposome and GNP systems are similar in many aspects, the important differences are explained by their respective physical properties. Cycloaddition is a novel generic chemical tool for the facile in situ surface modification of liposomes. Fluorescence resonance energy transfer was used to demonstrate that the reaction takes place at the surface and a colorimetric assay was developed to follow the reaction in time without the need for any equipment... 

The Cu(I) catalyzed azide/alkyne Huisgen 1,3-dipolar cycloaddition is a very powerful conjugation reaction for surface modification of liposomes. The... 

Surface Modifications of Liposomes for Recognition and Response to Environmental Stimuli... 

We have investigated the surface modification of liposomes for functionally mediated delivery systems including the modihcation of carbohydrates, proteins, and polymers. The fluidity and membrane state of liposomes will be discussed in terms of promoting their recognition and response to environmental stimuli. 

Figure 5 shows three methods for the formation and surface modification of liposomes. 

FIG. 5 Methods for surface modifications of liposomes, (a) Direct mixing of lipids and receptor-modified lipids, (b) Direct reaction of intermediate-modified liposomes and ligands, (c) Insertion of modified receptors into the liposomal bilayer. 

Described in the following are reported examples of compounds that have been used in the surface modification of liposomes. 

The surface modification of liposomes is a useM way to impart functionality, especially target sensitivity, to liposomes. In physical targeting, some characteristic of the environment is used either to direct the liposomes to a particular anatomical location or to cause a selective release of its contents as shown in Table 1, but we limit the discussion here to temperature- and pH-sensitive liposomes and immunoadjuvants. 

The concept of de-PEGylation can be applied to the development of nanoparticle-based drug delivery systems. PEG is used for the modification of liposomes to increase their blood circulation time [38], However, it also prevents cellular uptake, resulting in a decrease in therapeutic efficiency thus, modifications of the liposome surface with PEG interfere with membrane fusion to the cell membrane and liposome decomposition [39]. One of the possible strategies to solve this problem is to cleave the PEG chains after the nanoparticle reaches the target site (Fig. 9). This system of de-PEGylation of liposomes is also useful in avoiding the immune... 

An interesting approach to achieve an increased uptake after oral administration of colloidal drug carriers is to use site-specific adherence through surface modification of the colloidal systems with various entities, e.g. lectins, to a selected site in the gastrointestinal tract (124). By using this approach. Lehr et al. were able to achieve an enhanced adherence of polystyrene particles to enterocytes in vitro (125). Similarly, Rubas et al. were able to enhance the uptake of liposomes into Peyer s patches in vitro through incorporation... 

It may prove possible to construct stable artificial ion channels in phospholipid membranes by attaching phosphate groups and long hydrocarbon chains to spacer molecules such as calixarenes (Figure 11.8a,b) cycloamyloses or other similar molecules. It should be feasible to localise and control surface coverage of aqueous layers with tailor-made channels (Figure 11.8c). Modification of liposome-like assemblies may also be possible. 

Chemical modification of liposome surfaces via a copper-mediated [3-I-2] azide-alkyne cycloaddition reaction based on click chemistry and monitored by a colorimetric assay... 

Ng, L. Yuba, E. Kono, K. Modification of liposome surface with pH-responsive polyampholytes for the controlled-release of drugs. Res. Chem. Intermed. 2009, 35,1015-1025. 

The specific applications require different bulk and surface properties of liposomes. Among others, for example, the unique properties of stealth, targeted, and cationic liposomes could be achieved by surface modification. Figure 1 illustrates examples of liposomal surface modifications for such specific applications. The goals of these surface modifications are (1) to increase liposome longevity and stability in the circulation, (2) to change liposome biodistribution, (3) to achieve targeting effect, and (4) to impart to liposomes some unusual properties such as pH or thermal sensitivity. 

The surface modifications of bilayers were investigated for stimuli-sensitive applications of liposomes. The preparations of temperature-, pH-, target-, and immunosensitive liposomes and their results were discussed. 

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