ИСТИНА

Liposomes are spherical particles made of lipid bilayer with size ranging from tens to hundreds of nanometers. In addition to about a dozen of already approved liposome-based medicines, there are several hundreds of formulations being in different stages of clinical trials. Microgel (µG) is a micrometer- or submicrometer-sized particle composed of cross-linked polymer chains. Such particles can be made temperature and/or pH sensitive: they shrink (decrease in size) and swell (increase in size) in response to change in these parameters. We propose to adsorb anionic liposomes (Deff ≈ 60 nm) onto positively charged µGs (Deff ≈ 350 nm) and then use temperature-induced collapse of µGs to trigger release of liposomal contents. Complexation was confirmed with Dy-namic Light Scattering as aggregation occurs upon neutralization of µG surface charge upon adsorption of liposomes. At the same time, such µG-to-liposome ratio can be chosen so that aggregation is suppressed which makes the system applicable for drug delivery purposes. We further show that adsorption of lipo-somes onto µGs is not accompanied with release of liposomal contents (NaCl or fluorescein solution), in other words, liposomal membrane stays intact upon interaction with µG surface. Release of liposomal contents only takes place upon temperature-induced collapse of microgel. Interestingly, it was found that kinetics of fluorescein release from lipo-somes depend on the structure of the collapsing µG-liposome complex. Fluo-rescein is released much faster when all the surface of µG particle is covered with liposomes (Fig. 1, left) in comparison to the complex where only a few liposomes are adsorbed onto each µG particle (Fig. 2, right). These findings are used to propose a mechanism for liposome contents release upon temperature-induced collapse of µG: the surface area of µG decreases dramatically, thus making the adsorbed liposomes to smash together. This leads to significant dis-tortions of liposomal membranes (maybe even distruction of liposomes) and, as a result, significant increase in permeability. This work was supported by Russian Science Foundation (project 14-13-00255).