On the mechanism of payload release from liposomes bound to temperature-sensitive microgel particles

Abstract

Thermosensitive N-isopropylacrylamide based cationic microgels (μG) were synthesized and complexed with anionic liposomes containing encapsulated antitumor antibiotic Doxorubicin (Dox). Compositions of the resulting complexes, in terms of a liposome-to-μG number ratio N, varied from N = 0.5 to a saturated complex with N = 30 where the surface of μG particles is fully covered with liposomes. The microgels collapse when heated from 25 up to 50 °C and the surface area of a microgel particle decreases. The thermo-induced contraction is accompanied with release of Dox from the μG-bound liposomes while a significant fraction of DOX is released for both the unsaturated and saturated complexes. Therefore, two mechanisms are hypothesized for the thermo-induced Dox release. The first one is due to temperature-induced conformational changes of polymer chains, subsequent rearrangements at liposome-microgel interface via liposome-microgel interaction. This mechanism can work for the complexes of any composition. The second process, namely a squeezing of liposomes via liposome-liposome interaction followed by Dox release can become significant for the saturated complex. The results we have obtained are of great interest for constructing multi-liposomal drug carriers, diagnostic systems and catalysts.