Vesosomal drug delivery system with multi-compartments for controlled and sustained release

Abstract

Liposomes are spherical structures enveloped by a lipid bilayer. They have been extensively studied to date due to their advantage of self-assembly, biocompatibility, good cellular/tissue uptake, and capability to carry large drug payloads. On the other hand, limitations still remain in multi-drug loading in a single carrier and controlling their release. On-demand drug release is a desirable feature in drug delivery systems to have more precise control over drug release, resulting in the reduction of drug payloads for safer and more economical medication. Light-triggered drug release systems have their benefits in being non-invasive, tissue-penetrable, and target-specific. However, most of proposed systems have not been realized for approved treatments because of the necessity of continuous light exposure, inability to meet an optimal cutoff size, and molecular interruptions. Herein, we devised a drug delivery system enabling the light-triggered sequential release of drugs through a multicompartment vesosomal system, in which smaller liposomes were encapsulated in a larger unilamellar vesicle. The lipid peroxidation of lipids in the liposomal form upon red-light-induced reactive oxygen species (ROS) caused the liposomes to release encapsulated contents. Liposomes composed of different unsaturated/saturated lipid fractions along with a photosensitizer were loaded into a vesosomal system. Upon light exposure, ROS-vulnerable liposomes release their contents while the contents in ROS-non-vulnerable were released after some delay. This system was further investigated in vitro with calcein-loaded vesosomes and doxorubicin-loaded vesosomes for demonstrating the controlled and sustained release of contents, respectively. Moreover, Caenorhabditis elegans was tested as an in vivo model due to its similarity of the epidermis layer to the human skin and showed inhibited growth in the red-light-exposed group. Through this work, we believe that our work could pave a road for intelligent multicompartmental drug delivery systems, enabling on-demand drug delivery.