3.MICRO AND NANO SYSTEMS (cont)
3.2.Liposomes
Liposomes are small spherical vesicles in which one or more aqeous compart- ments are completely enclosed by molecules that have hydrophilic and hydrophobic functionality such as phospholipids and cholesterol. Properties of liposomes vary substantially with composition, size, surface charge and method of preparation. They can be formed as single lipid bilayer or in multiple bilayers. Liposomes containing one bilayer membrane are termed small unilamellar vesicles (SUV) or large unilamellar vesicles (LUV) based on their size ranges (Mozafari and Sahin2005). If more than one bilayer is present then they are called multilamellar vesicles (MLV). Liposomes are commonly used as model cells or carriers for various bioactive agents including drugs, vaccines, cosmetics and nutraceuticals.The introduction of positively or negatively charged lipids provides the liposomes a surface charge. Drugs associated with liposomes have markedly altered pharma- cokinetic properties compared to free drugs in solution. Liposomes are also effective in reducing systemic toxicity and preventing early degradation of the encapsu- lated drug after introduction to the body. They can be covered with polymers such as polyethylene glycol (PEG) – in which case they are called pegylated or stealth liposomes – and exhibit prolonged half-life in blood circulation (Mozafari et al 2005). Furthermore, liposomes can be conjugated to antibodies or ligands to enhance target-specific drug therapy. Visser et al (2005) studied targeting of pegylated liposomes loaded with horse radish peroxidase (HRP) and tagged with transferrin to the blood-brain barrier in vitro. They have shown effective targetting of liposomes loaded with protein or peptide drugs to the brain capillary endothelialcells and suggested that the system is an attractive approach for drug delivery to brain. Lopez-Pinto and coworkers (2005) examined the dermal delivery of a lipophilic drug, minoxidil, from ethosomes versus classic liposomes by appliying the vesicles non-occlusively on rat skin. They studied the permeation pattern, depth into the skin and the main permeation pathway of different liposomal systems. Ozden and Hasirci (1991) prepared small unilamellar vesicles composed of phosphatidyl- choline, dicetyl phosphate and cholesterol and entrapped glucose oxidase in them. They obtained loading efficiency as one protein per liposomal vesicle.Liposomes containing the expression vector pRSVneo coding for neomycin phosphotransferase–II were studied by Leibiger et al (1991) for a gene transfer into rat liver cells in vivo. After intravenous application of liposomes to male Wistar-rats, nonintegrated vector DNA was detected by blot-hybridisation in isolated nuclei of hepatocytes. Cirli and Hasirci (2004) prepared calcein encapsulated reverse phase evaporation vesicles carrying photoactive destabilization agent suprofen in the lipid bilayer. They investigated the effect of UV photoactivation of liposomal membrane- incorporated suprofen on the destabilization of the liposome bilayer and the release of encapsulated calcein as a model active agent.Liposomes are also studied as carriers for cells, genes or DNA fragments. Ito et al (2004) studied the effect of magnetite cationic liposomes which have positive surface charge to enrich and proliferate Mesenchymal stem cells (MSCs) in vitro. Kunisawa et al (2005) established a protocol for the encapsulation of nanoparticles in liposomes, which were further fused with ultra violet-inactivated Sendai virus to compose fusogenic liposomes and observed that fusogenic liposome demonstrated a high ability to deliver nanoparticles containing DNA into cytoplasm. Ito et al (2005) investigated whether coating the culture surface with RGD (Arg–Gly–Asp) conju- gated magnetite cationic liposomes (RGD-MCLs) was able to facilitate cell growth, cell sheet construction and cell sheet harvest using magnetic force without enzymatic treatment. They reported that cells adhered to the RGD-MCLs coated bottom of the culture surface, spreaded and proliferated to confluency. Detachment and harvesting of the cells did not need enzymatic process. Fuentes et al (2003) studied the adjuvan- ticity of two gamma inulin/liposomes/Vitamin E combinations in the mouse, in contraceptive vaccines by using sperm protein extracts or a synthetic HE2 peptide (Human Epididymis gene product; residues 15–28) as antigen. They showed that the gamma inulin/liposomes/Vitamin E combination, with sperm protein extracts, was better than Freund’s adjuvant. When the synthetic HE2 peptide was used as antigen, the gamma inulin/liposomes/Vitamin E combination was less effective than Freund’s adjuvant.Vierling et al (2001) published a review on fluorinated liposomes made from highly fluorinated double-chain phospho- or glyco-lipids as well as fluorinated lipoplexes, e.g. complexes made from highly fluorinated polycationic liposper- mines and a gene. The properties of the fluorinated lipoplexes including stability and in vitro cell transfection in the presence of serum or bile were reported. El Maghraby et al (2004) showed that incorporation of activators (surfactants) into liposomes improved estradiol vesicular skin delivery. They examined the interactions of additives with dipalmitoylphosphatidylcholine (DPPC) membranes by using high sensitivity differential scanning calorimetry. Lopes and colleagues (2004) investigated the encapsulation of acid (AD) and sodium diclofenac (SD) in small unilamellar liposomes (SUV) prepared by sonication from multilamellar liposomes containing soya phosphatidylcholine and diclofenac at various propor- tions. The interactions of the drug with the bilayers were examined. They proposed a schematic model for interaction of SD with phosphatidylcholine of the liposomes in which the diclofenac anion interacts with the ammonium group of the phospho- lipid and the dichlorophenyl ring occupies a more internal site of bilayer near phosphate group. Simard et al (2005) prepared multilamellar vesicles by shearing a lamellar phase of lipids and surfactants. They reported formation of vesicles with mean diameter of less than 300 nm in which hydrophilic drugs can be loaded with high yield. They coated the vesicles with PEG and loaded them with 1-d-arabinofuranosylcytosine. Following injection of the vesicles intravenously to rats they observed that the surface-modified liposomes exhibited longer circulation times compared to uncoated liposomes.Koynova and MacDonald (2005) examined the lipid exchange between model lipid systems, including vesicles of the cationic lipoids ethyl dimyristoyl phosphatidylcholine, ethyl dipalmitoyl phosphatidylcholine or their complexes with DNA, and the zwitterionic lipids by using differential scanning calorimetry. They observed that, exchange via lipid monomers was considerably more facile for the cationic ethylphosphatidylcholines than for zwitterionic phosphatidylcholines and for the cationic liposomes. The presence of serum in the dispersing medium strongly promoted lipid transfer between cationic vesicles while almost no effect was reported for zwitterionic liposomes. This phenomenon was proposed as an important point for the application of cationic liposomes as nonviral gene delivery. Foco et al (2005) studied the delivery of sodium ascorbyl phosphate (SAP), an effective oxygen species scavenger to prevent the degenerative effects of UV radiation on skin. SAP was encapsulated into liposomes to improve its penetration through the stratum corneum into the deeper layers of the skin. They prepared two types of multilamellar vesicles, one from non-hydrogenated and the other from hydrogenated soybean lecithin, together with cholesterol. Sinico et al (2005) studied transdermal delivery of tretinoin and examined the influence of liposome composition, size, lamellarity and charge on transdermal delivery. They studied positively or negatively charged liposomes of different types, i.e. multilamellar vesicles (MLV) or unilamellar vesicles (ULV), prepared from hydrogenated soy phosphatidylcholine (Phospholipon® 90H) or non-hydrogenated soy phosphatidyl- choline (Phospholipon® 90) and cholesterol, in combination with stearylamine or dicetylphosphate. It was reported that negatively charged liposomes strongly improved newborn pig skin hydration and tretinoin retention.Arcon et al (2004) encapsulated an anticancer agent, cisplatin, in sterically stabilized liposomes and studied the systems with extended X-ray absorption fine structure (EXAFS) method, and concluded that the liposome-encapsulated drug is chemically stable and does not hydrolyze. Sapra and Allen (2003) published a review article about the ligand-targeted liposomes (LTLs) for the delivery of anticancer drugs. In this article, new approaches used in the design and optimization of LTLs was discussed and the advantages and potential problems associated with their therapeutic applications were described.
Source:
Nanomaterials and Nanosystems for Biomedical Applications
NESRIN HASIRCI
Middle East Technical University, Faculty of Arts and Sciences, Department of Chemistry, Ankara 06531, Turkey
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