Also, the charge of the outer membrane affects the distribution and stability of the liposome. Negatively charged selleck catalog liposomes were believed to be more rapidly removed from circulation than neutral or positively charged liposomes; later studies have indicated that the type of negatively charged lipid affects the rate of liposome uptake by the reticule-endothelial system. For example, liposomes containing negatively charged lipids that are not sterically shielded (phosphatidylserine, phosphatidic acid, and phosphatidylglycerol)
are cleared more rapidly than neutral liposomes of similar composition. However, liposomes containing sterically shielded lipids (ganglioside-GM1 and phosphatidylinositol) are cleared Inhibitors,research,lifescience,medical even more slowly than neutral liposomes . Consequently, scientists have attempted to modify the liposomal structure in order to improve liposomal penetration across biological membranes and into their target Inhibitors,research,lifescience,medical organs. Targeted liposome-based system was suggested after conventional stealth liposomes failed to evade uptake of active molecules by
sensitive normal cells or nonspecific targets . In addition, a targeted ligand can further increase the rate of liposomal drug accumulation in the ideal Inhibitors,research,lifescience,medical tissue or cells via overexpressed receptors, antigen and unregulated selectin [40, 41]. Peptides, proteins, and antibodies have been mostly studied as a ligand for directing drug-loaded liposomes into sites of action, due to their molecular Inhibitors,research,lifescience,medical structures, which are essentially composed by known amino acid sequences (Figure 1). The main advantage of these sellckchem structures is the relatively large quantities of drug that can be incorporated into one compartment. However, liposome structures present various problems Inhibitors,research,lifescience,medical related to the administration pathway. Orally administration is difficult because the low pH of the stomach
and the presence of bile salts tend to destabilize the liposome complex. Liposomes are very sensitive to pH, light, magnetism, temperature, and ultrasonic waves besides, liposomes are highly susceptible to destruction via uptake by the reticule-endothelial system of the macrophages. A way of protecting liposomes was studied and patented and consisted in increasing stable bilayers and regulating the release profile of the liposome [36, 40]. Although liposomes contain Dacomitinib an outer lipophilic membrane that increases their permeability across membranes, some biological barriers such as the BBB remain impenetrable. The development of a suitable liposomal carrier to encapsulate active compounds is very promising. These liposomes, also named targeted liposomes, are stable enough to be carried out to the brain across the BBB, with the appropriate surface characteristics for an effective targeting and for an active membrane transport.