Preparation and Characterization of Drug Liposomes by pH-Gradient Method

Abstract

During last five decades, liposomes are well developed as delivery carriers for various molecules and can form unilamellar or multilamellar lipid vesicles. To design liposomal formulations for tumor therapy, administration by intravenous injection is a main option. Considering that sometimes anticancer drug needs higher dose (e.g., ~50 mg/m² for doxorubicin), the stable drug-loading method must be explored for the practical use of drug liposomes during storage and in circulation. Conventional preparation approaches are impossible to reach higher drug encapsulation because of the nature of the poor drug solubility. The issue of low drug-loading rate would make therapeutic potential of drugs in low levels and cannot reach clinic use. The development of remote loading can also overcome the instability when loading with high internal concentrations of drugs. Transmembrane pH gradients in liposomal carrier can be helpful to promote the encapsulation of various commonly used drugs and fluorescent probes. In fact, pH-gradient method is the first use of remote loading approaches. The transmembrane ion gradients can be constructed by adopting salts composes either weak bases or weak acids. The degree of ionization of these drugs is pH dependent. Their ionized forms have a very low permeability coefficient, while their unionized species have high permeability and can diffuse relatively fast across liposome lipid bilayer to reach the intraliposomes. pH-gradient method provides a basic insight to develop other remote loading methods.