Phospholipids are the major component of
liposomes, which make them to be less toxic, biodegradable, and biocompatible. The bilayer of phospholipids prevents also the active form of the drug from breaking down before it reaches the tumour tissue and in this way exposure of the normal tissue to the drug is minimized. The therapeutic index of the drug is then increased by two mechanisms: on one hand, a greater amount of the active drug reaches the tumour cells and an increased MAPK Inhibitor Library cytotoxic effect is obtained and, on the other hand, side effects are also reduced as a consequence of the drug encapsulation. Liposomal formulations Inhibitors,research,lifescience,medical have an additional effect on drug metabolism by decreasing its enzymatic degradation . Liposomes can be produced by different methods. Inhibitors,research,lifescience,medical Stability of both the bilayer and the incorporated drugs depends on lipid composition and cholesterol content. Their size ranges from 25 to 100nM and is determined by the maximum quantity of drug stored within the membrane and its flexibility. The lower size limit avoiding liposomes may enter the normal capillary vessels whereas the upper limit Inhibitors,research,lifescience,medical is still within the tumour vasculature and enables the cytotoxic agent to reach the tumour bed; in order to produce its effect, the active drug needs to readily extravasate through the vascular defects present in the vessels surrounding cancer cells as a consequence of Inhibitors,research,lifescience,medical neoangiogenesis
phenomena induced by neoplastic cells . In this way, liposomes below this threshold have the potential to accumulate in the
tumour bed after passive drug entry and boosted by impaired lymphatic drainage. This phenomenon has been described as “enhanced permeability plus retention effect” . One more factor related to liposome’s size is that the bigger they are the greater the uptake by the reticuloendothelial system and, therefore, more rapid the drug is metabolized . As the time liposomes are retained in the circulatory system is reduced, the drug they are carrying might not reach cytotoxic levels in the tumour tissue. The size of the nanotransporter Inhibitors,research,lifescience,medical could be reduced, but then less drug quantity should be transported. One method that has proven to be effective in overcoming this obstacle without compromising the quantity of chemotherapeutic agent delivered to the tumour consists in coating these delivery systems with polymers, in particular, with polyethylene glycol (PEG) which allows liposomes to escape from the immune system and, therefore, increase “in vivo” STK38 circulating time . Studies have shown that, when manufactured in this way, pegylated liposomes have a longer half-life than nonpegylated (ranging from a few hours to 45 hours) . However, the presence of PEG may act as a barrier between the drug and the tumour cells hindering the delivery of the cytostatic. Therefore, future improvements should be directed to improve this aspect, particularly in the case of breast cancer.