Multifunctional liposomes

Among the several drug delivery systems, liposomes - phospholipid nanosized vesicles with a bilayered membrane structure - have drawn a lot of interest as advanced and versatile pharmaceutical carriers for both low and high molecular weight pharmaceuticals. At present, liposomal formulations span multiple areas, from clinical application of the liposomal drugs to the development of various multifunctional liposomal systems to be used in therapy and diagnostics. This chapter provides a brief overview of various liposomal products currently under development at experimental and preclinical level. 

Many of the listed functions/properties of liposomes, such as longevity, targetability, stimuli-sensitivity, ability to deliver drugs intracellularly, etc. could, theoretically, be combined in a single preparation yielding a so-called multifunctional liposomal nanocarrier (155) (see Fig. 1). 

Fig. 20.12 Schematic illustration of multifunctional liposome and the noncovalent sinface modification via host-guest interaction...

Recently, Kang et al. reported the development of the first aptamer-conjugated, multifunctional liposome nanostructure. Similar to the drug-encapsulated nanoparticles previously mentioned, PEG spacers were incorporated to increase the systemic circulation time of the liposome and well as to prevent its uptake by macrophages in the liver and other organs, thus increasing it delivery efficacy. 

Nonviral vector systems are usually either composed of a plasmid based expression cassette alone ( naked DNA), or are prepared with a synthetic amphipathic DNA-complexing agent (84, 88). Gene delivery systems based on nonviral vectors mainly comprise cationic liposomes, DNA-polymer-protein complexes, and mechanic administration of naked DNA. An idealized/optimized multifunctional nonviral gene delivery system is depicted in Figure 13.4. 

In recent years, pharmaceutical patents accounted for almost 25% of the nonfood patent activity. Pharmaceutical applications, particularly those involving liposomes, should require increasing quantities of refined lecithins. An increased demand for lecithin as a dietary supplement is also anticipated, as the result of dietary reference intakes being established for choline. Besides being a multifunctional food ingredient, lecithin has the benefit of being a widely recognized health food. 

In spite of these formidable challenges, the attractiveness of oral route has fueled the exploration of an incredibly diverse set of strategies to deliver proteins and peptides and the subject has been exhaustively reviewed. The various approaches include permeation enhancers, enzyme inhibitors, mucoadhesives, multifunctional matrices that simultaneously incorporate the above strategies, enteric coatings that offer protection from the acidic environment of the stomach, encapsulation (liposomes, microspheres, and nanoparticles), pH-sensitive polymers, microemulsions, carriers (delivery agents), and protein modification either to simply enhance permeability or to exploit specific transporters. While proof-of-concept has been demonstrated with most of these delivery systems in animal... 

For a further development of this method i.e., the preparation of multifunction-alized capsules, a series of multicompartment polymeric capsules were successfully constmcted. For example, Stadler et al. [19] synthesized multicon tartment polymeric capsules with embedded liposomes in the shell via the LbL technique by using poly(styrene sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) as the polyelectrolytes and 50nm zwitterionic l,2-dioleoyl-i n-glycero-3-phosphochohne (DOPC) liposomes as the cargo. The TEM images (Fig. 6.9) clearly show the encapsulated liposomes in the polymeric shell. 

There are countless fabrication techniques available for producing multifunctional nanoparticles. For liposomes, one such method is called the film hydration technique. In it, multilamellar liposomes are spontaneously formed after a dried lipid solution is exposed to an aqueous solution and mechanically agitated [23]. For unilamellar liposomes, the extrusion technique can be utilized in which multilamellar liposomes are extmded through a porous membrane in the presence of the drug and then undergo a freeze-thaw... 

This versatile modifiable property allows liposomes to encapsulate functional molecules in the interior, inserted in the bilayer or attached on the bilayer membrane surface. Hence, they have been considered for application in multifunctional platforms, that is, therapy and imaging. They protect the amphiphilic, hydrophobic, and hydrophilic therapeutic agents against various threats that lead to their immediate dilution and degradation. 

The >20 natural amino acids and their synthetic derivatives constitute an abundant monomer source for the construction of multifunctional polypeptides. Like the micelles, liposomes, and hydrogels described above, photoresponsive polypeptides can be successfully constructed by introducing some photoresponsive moieties such as coumarin, 2-nitrobenzyl, cinnamyl, and... 

Hofmann AM, Wurm F, Huhn E, Nawroth T, Langguth P, Kney H (2010) Hyperbranched polyglycerol-based Lipids via oxyanionic polymerization toward multifunctional stealth Liposomes. Biomacromolecules 11 568-574... 

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