Dernière modification: 2017-10-03
Résumé
Liposomes are spherical and microscopic vesicles with a diameter ranging from 20 nm to a few thousands nm. Composed of an aqueous solution core surrounded by a hydrophobic membrane forming lipid bilayers, liposomes can be hence loaded with hydrophobic and/or hydrophilic molecules. [1, 2]
Loading drugs into liposomes can increase the therapeutic ratio by reducing drug concentrations in normal tissues and raising their concentrations in cible tissues. Although this strategy has proven advantageous in certain circumstances, many drugs are highly hydrophobic and non ionizable and cannot be loaded into liposomes through conventional means. Indeed, low encapsulation efficiency, non-encapsulated drug loss, remaining of organic solvents and rapid in vivo drug leakage of bilayer-permeable drug species are the principal limits of passive drud encapsulation méthods. [2, 3]
From these physicochemical considerations and methodological problems, we describe in the present a method of active drug encasulation. The basic concept is based on two simple phenomena. First, a given lipophilic molecule can easily penetrate the lipid bilayer, but it will gain a charge while entering the internalcompartment, provided the internal compartment possesses a low pH. Second, as an ion, that molecule will no longer be able to cross the bilayer freely. Thus, a pH gradient is the driving force to translocate and retain the amphiphilic weak bases and acids in the preformed liposomes [4]. With this method, doxorubicin, was loaded in a drug-to-lipid ratio (D/L) of 0.3 w/w with an encapsulation efficiency of nearly 100% and excellent in vitro stability, especially when phospholipids with long and saturated fatty acid chains are used for the liposome preparation. This approach is expected to improve and accelerate development of liposomal formulations for clinical applications [3,4]