ИСТИНА

Microgel-liposome (µG-liposome) complexes could find biomedical applications such as controlled drug delivery and release. These complexes could have several advantages over conventional liposomal formulations already approved for treatment. Thermosensitive microgels (µGs) with pH-dependent charges were prepared by precipitation copolymerization of 10 mol% 3-(N,N,-dimethylamino)propylmethacrylamide (DMAPMA) with N-isopropylacrylamide (NIPAM) in the presence of 4 mol% cross-linker bis-acrylamide (BIS). The presence of positively charged DMAPMA groups allows complexation with oppositely charged liposomes. The small unilamellar mixed liposomes composed of zwitter-ionic dipalmitoylphosphatidylcholine (DPPC), negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (PS), Cholesterol (6:3:1 by mass) were obtained via sonication. We demonstrate in this work that anionic unilamellar liposomes of size 60 nm can be adsorbed without distruction onto oppositely charged µGs 350 nm in diameter. When the surface of µG is fully covered with liposomes (2a), then a fast release of all liposomal contents occurs upon collapse of µG (2b). At least two mechanisms can be proposed for how µG induces leakage upon collapse. In the first mechanism, polymer chains interacting with PS molecules (1a), drag the latter out upon collapse, causing defect formation and consequent leakage (1b). In the second, the leakage happens because the surface of µG particle changes drastically, thus causing liposomes to smash together (3a, 3b). Such liposome-liposome interaction can lead to change of curvature of lipid membrane, defects formation, fusion or maybe even destruction. All of these events are usually accompanied with release of contents. It was found that if the surface of µG is covered with just a few liposomes, then almost no leakage from adsorbed vesicles is observed upon temperature-induced collapse in comparison to free liposomes. This supports the mechanism where liposome-liposome interaction is most significant for release of contents of liposomes upon collapse (3a, 3b). This work was supported by Russian Science Foundation (project 14-13-00255).