Liposomes Encapsulating Model Drugs and Silver Nanoparticles for Illumination Based Drug Release

Abstract

Drug delivery systems include the delivery of the drug within the nanocarriers targeted to the diseased site, thereby the side effects caused by the interaction of the drugs with the untargeted regions are limited. One of the common nanocarriers employed is the liposomes, which are polymolecular aggregates of certain amphipathic molecules, formed in aqueous solution. The unique architecture of liposomes provides a useful platform for incorporation of hydrophilic and/or hydrophobic molecules within the core and/or the bilayer, which has opened the way for the usage of liposomes as nanocarrier systems in pharmaceutical applications. However, this type of therapy still needs improvement because of limitations in stability, encapsulation efficiency, the interaction between the nanocarrier and the cell, and also problems related to rapid clearance by reticuloendothelial system, which has lead researchers to produce novel ways. Photothermal triggered drug release is one of the novel drug delivery systems which has the potential in delivering higher amounts of drugs to the diseased site, aiming to deliver the encapsulated compound effectively while minimizing the toxicity. This type of therapy based on the phase transition of liposome layers as a result of local temperature increase following the exposure of light, and consequently the release of the encapsulated content. In this study, to develop a system that can serve the release of payload upon light exposure, the silver nanoparticles (AgNPs) which have remarkable optical features, were encapsulated within the liposomes, and the drug release was tested upon illumination. The synthesis of thermosensitive liposomes loaded with model drugs (i.e. rhodamine) and AgNPs, as a novel photothermal drug delivery system was performed successfully in a continuous flow millireactor. Analytical techniques including dynamic light scattering (DLS), UV-Vis spectrophotometry or transmission electron microscopy (TEM) were employed to characterize the efficiency of the production, the encapsulation of the AgNPs and the drug release performance. Results showed that liposomes can be produced with the intended size in a controllable manner by changing millifluidic conditions. Also, the encapsulation of AgNPsin liposomes was confirmed with DLS results and TEM images. The association between liposomes and AgNPs revealed that it can be regarded as a mixture of incorporation and encapsulation. Drug release profiles characterized by fluorescence intensity in a plate reader or under a fluorescence microscope showed promising results. However, the system needed further modification to demonstrate the drug release assisted by the photothermal effect of AgNPs, such as to have the ability to release drugs on demand by operating as an opening and closing mechanism, or to function as a therapeutic system capable of real-time monitoring in addition to drug release on demand.<br/