Construction of nanoscale multicompartment liposomes for combinatory drug delivery

Abstract

Liposomes are clinically used delivery systems for chemotherapeutic agents, biological macromolecules and diagnostics. Due to their flexibility in size and composition, different types of liposomes have been developed varying in surface and structural characteristics. Multicompartment liposomes constitute an attractive drug carrier system offering advantages in terms of inner vesicle protection, sustained drug release and possibility for combinatory (cocktail) therapies using a single delivery system. However, all previously described methodologies for multicompartment or multivesicular liposomes resulted in micrometer-sized vesicles limiting most pharmaceutical applications. In this work we report formulation of nanoscale multicompartment liposomes which maybe applicable for systemic administration. A small unilamellar vesicle (SUV) aqueous dispersion (DOPC:DOPG:CHOL) was used to hydrate a dried film of different lipid contents (DMPC:CHOL), followed by extrusion. The system was characterised by techniques such as photon correlation spectroscopy (PCS), zeta potential measurement, transmission electron microscopy (TEM) and laser scanning confocal microscopy (LSCM). We observed a single, multicompartment vesicle population composed of the two different bilayer types of approximately 200 nm in mean diameter rather than a mixture of two independent vesicle populations. In the case of tumour therapy, such multicompartment liposome systems can offer a single carrier for the delivery of two different modalities.