Structure
- Basic Structure: Liposomes consist of a lipid bilayer membrane primarily composed of synthetic derivatives of naturally occurring phospholipids, namely phosphatidylcholine. This phospholipid layer encircles an aqueous center.
- Stability and rigidity can be altered.
-Cholesterol is also frequently added in order to increase stability and rigidity.
- Surface charge varies according to pH and the head group composition of the lipids in the bilayer.
*Liposomes with a neutral surface charge have a relatively low tendency to be cleared by reticuloendothelial system (RES) cells and tend to aggregate well. Having choline or ethanolamine as the lipid head group leads to a neutrally-charged liposome.
*Negatively charged liposomes tend to be phagocytized by macrophages, so molecules like phosphatidylinositol are added to inhibit macrophage uptake.
*Positively charged liposomes often interact with serum proteins and are likely to be taken up by the RES, making their nucleic acid transfection capabilities limited.
- Surface hydration/steric modification is the process of modifying a liposome's membrane with hydrophilic polymers.
*Adding gangliosides like GM1 and conjugated lipids like polyethylene glycol will allow the liposome to decrease aggregation and avoid detection by the immune system.
- The fluidity, and thus permeability, of a liposome's membrane can be altered by the addition of certain molecules or changes in internal conditions.
-Heat and pH affect fluidity, which is why remote heating of cells can be used to trigger the release of a drug by a liposome.
- The rate of clearance by the RES increases as the liposome's size increases.
Targeting
-Unfortunately, PEG interferes with protein binding, so phosphatidylethanolamine and antibodies have been added to PEGylated liposomes, allowing for protein interactions while retaining long circulation time. |
Preparation
1.) Various lipids are mixed together and dissolved in an organic solvent like chloroform.
2.)This solution is evaporated into a dry lipid film. 3.) The film is hydrated with water and often dextrose. 4.) The resulting mixture is heated and sonicated. 5.) The sonicated mixture is filtered to yield the final liposome. -The drug will be added at one of these stages depending on its particular composition (Templeton, et al., 1997). |
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Problems with Liposomes
- Liposomal membranes may negatively interact with proteins in the patient’s body.
-Many liposomes are designed to be pH-sensitive, but this sensitivity may be altered when the liposome is bound by other proteins.
-Specific proteins may also facilitate greater immune recognition of the liposome, making it more prone to clearance before it can reach its target.
- Liposomes are potentially toxic themselves if they get distributed to non-targeted areas.
-Inflammation caused by tumor growth or infection has been shown to result in liposome accumulation, which results in a higher than expected effective dose, similar to dose dumping. Liposomes may become trapped at the site of injection or be retained in lymph nodes, leading to potential toxicity due to these concentrated doses.
Allen, T. M. and Cullis, P. R. 2013. Liposomal drug delivery systems: from concept to clinical applications. Advanced Drug Delivery Reviews. Vol 65, No. 1: 36-48.
Lian, T. and Ho, R.J. 2001. Trends and developments in lioposomal delivery systems. Journal of Pharmaceutical Sciences. Vol 90, No. 6: 667-680.
Lian, T. and Ho, R.J. 2001. Trends and developments in lioposomal delivery systems. Journal of Pharmaceutical Sciences. Vol 90, No. 6: 667-680.