Introduction
Liposomes are vesicles consisting of one or more phospholipids bilayers encasing an aqueous compartment as seen in Figure 1 (1-3). By allowing encapsulation of drugs, DNA or proteins within the compartment, it can facilitate drug movement to particular targets while eliciting varying pharmacokinetic characteristics that enhances the therapeutic effect of delivered contents (2, 3). Due to their ease of preparation, versatility and biologically non-toxic nature, liposomes have been a focus of medical research in hopes of improving therapeutic outcomes for drugs with unfavourable pharmacokinetics (1).
One such aforementioned drug is Doxorubicin, a widely used chemotherapeutic agent used in the treatment of cancer conditions such
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Doxorubicin is an anti-cancer agent which should only be affecting cancerous tissues but conventional doxorubicin lacks the ability to differentiate normal from cancerous cells and affects all tissues based on its systemic circulation (2, 4). Liposomal doxorubicin as nanocarriers size within the nano to micro ranges being larger than conventional small drug molecules allows manipulation of a phenomenon called the enhanced penetration and retention (EPR) (2, 4). EPR is a passive targeting effect in which the molecule takes advantage of tumour pathophysiological characteristics that extravasate macromolecules into cancerous tissues while depleting lymphatic drainages to prevent macromolecule clearance as seen Figure 5 (4).
Furthermore, current marketed liposomal doxorubicin features pegylation, in which liposomal doxorubicin is pegylated or otherwise known as coated with polyethylene glycol (13). The polyethylene glycol impedes detection by the mononuclear phagocyte system allowing it extended circulation periods without elimination (7, 13). Increases in circulation period compound aid to liposomes EPR effect in accumulating within cancerous
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Blanco E, Ferrari M. Emerging nanotherapeutic strategies in breast cancer. Breast (Edinburgh, Scotland). 2014 Feb;23(1):10-8. PubMed PMID: 24215984. Epub 2013/11/13. eng.
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11. Haran G, Cohen R, Bar LK, Barenholz Y. Transmembrane ammonium sulfate gradients in liposomes produce efficient and stable entrapment of amphipathic weak bases. Biochimica et Biophysica Acta (BBA) - Biomembranes. 1993 9/19/;1151(2):201-15.
12. Accardo A, Aloj L, Aurilio M, Morelli G, Tesauro D. Receptor binding peptides for target-selective delivery of nanoparticles encapsulated drugs. International journal of nanomedicine. 2014;9:1537-57. PubMed PMID: 24741304. Pubmed Central PMCID: PMC3970945. Epub 2014/04/18. eng.
13. Allen TM, Hansen C, Martin F, Redemann C, Yau-Young A. Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. Biochimica et Biophysica Acta (BBA) - Biomembranes. 1991
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...des dissolving of 100mg of PC into 15 ml ethanol and then this solution mixture is added drop-wise into a Vitamin C solution. Continuous stirring is required. The conditions like low temperature and moisture content can be achieved. The organic solvent is then evaporated and by maintaining pH at 7.4 of the phosphate buffer solution (PBS), the solvent traces are removed. The Liposome dispersion is then stored under vacuum overnight. The liposome size can be downsized by sonication. Liposome characterisation i.e. size and surface structure can be observed using cryo-transmission electron microscopy (cryo-TEM) (27).
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The cell plasma membrane, a bilayer structure composed mainly of phospholipids, is characterized by its fluidity. Membrane fluidity, as well as being affected by lipid and protein composition and temperature (Purdy et al. 2005), is regulated by its cholesterol concentration (Harby 2001, McLaurin 2002). Cholesterol is a special type of lipid, known as a steroid, formed by a polar OH headgroup and a single hydrocarbon tail (Wikipedia 2005, Diwan 2005). Like its fellow membrane lipids, cholesterol arranges itself in the same direction; its polar head is lined up with the polar headgroups of the phospholipid molecules (Spurger 2002). The stiffening and decreasing permeability of the bilayer that results from including cholesterol occurs due to its placement; the short, rigid molecules fit neatly into the gaps between phospholipids left due to the bends in their hydrocarbon tails (Alberts et al. 2004). Increased fluidity of the bilayer is a result of these bends or kinks affecting how closely the phospholipids can pack together (Alberts et al. 2004). Consequently, adding cholesterol molecules into the gaps between them disrupts the close packing of the phospholipids, resulting in the decreased membrane fluidity (Yehuda et al. 2002).
Cancer is one of the leading causes of death worldwide as it can develop in almost any organ or tissue. Significant advances in understanding the cellular basis of cancer and the underlying biological mechanisms of tumour has been vastly improved in the recent years (Jiang et al. 1994). Cancer is a genetic disease which requires series of mutation during cell division to develop, it has characteristics which can be associated with their ability to grow and divide abnormal cells uncontrollable while in the mean time invade and cause nearby blood vessels to serve its need. Even though many people are affected by cancer today, the abilities which cancer cells own make it hard to find single effective treatment for cancer. The focus of research now lies on developing drugs which target cancer cells in the hope to cure cancer once and for all.
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displayed the ability of Vemurafenib (Figure 1), a current FDA approved drug for use in BRAFV600E mutant cancers, to hold PPGs. The binding of vemurafenib to BRAFV600E is facilitated through hydrogen bonding between protein residues of BRAFV600E (Figure 2) and two specific moities of vemurafenib: 7-azaindole moiety and sulfonamide NH residue. PPGs are bound to these moieties through nucleophilic substitution, creating caged prodrugs (Figure 3) with groups removable by UV light. The addition of these PPGs causes steric hindrance which inhibits the binding of vemurafenib to BRAFV600E,implementing temporal and spatial control of the administration of
plasma membranes, meaning animals and plants contain lipids. In this paper I will display and
Activity 3: Investigating Osmosis and Diffusion Through Nonliving Membranes. In this activity, through the use of dialysis sacs and varying concentrations of solutions, the movement of water and solutes will be observed through a semipermeable membrane. The gradients at which the solutes NaCl and glucose diffuse is unproportional to any other molecule, therefore they will proceed down their own gradients. However, the same is not true for water, whose concentration gradient is affected by solute ...
There are many functions lipids have. One of the main functions lipids are structural components in the cell. Lipids make up approximately 50% of the mass of most cell membranes. The lipids that are found in the cell membrane are called phospholipid. Phospholipid are the predominant lipids of cell membrane. Phospholipids aggregate or self-assemble when mixed with water, but in a different manner than the soaps and detergents. Because of the two pendant alkyl chains in phospholipids and the unusual mixed charges in their head groups, micelle formation is unfavorable relative to a bilayer structure.
WHO, W. H. (2008). Tradtional Medicine. available at http://www.who.int/mediacentre/factsheets/fs134/en/ retrieved on 9-11-11 at 10:30 pm.