Lipobeads (a combination of lipid bilayer and stimuli-sensitive cross-linked polymer network) is a good candidate for the conceptually new drug delivery system with release and activation of drug load regulated by bio-signals. In this work, our faculty-student research team focused on the aspects and properties of the spherical bipartite structures consisting of a hydrogel core coated by a lipid bilayer as including but not limited to: (1) two methods for preparation of lipobeads (polymerization within giant lipid vesicles and nano-/microgel-liposome mixing); in particular, substructures of hydrogel core and peripheral lipid part of lipobeads were distinguished by SEM without special sample preparation, justifying spontaneous formation of lipid bilayer on the surface of microgels and evidencing energetically favorable structural organization of the hydrogel/lipid bilayer assembly; (2) three types of polymer networks: “thermophobic” (shrink upon heating), “thermophilic” (swell upon heating), and degradable (de-cross-link under presence of a reductant); those hydrogel cores can provide the so-called “sponge-like”, “poration” and “burst” mechanisms of drug release, respectively; (3) de-cross-linking mechanism and kinetics of microgels degradable under presence of reducing agents; specifically, it was found that degradation of the polymer network is accompanied with swelling of microgels and the rates of degradation and swelling were measured to vary from hours to seconds depending on pH, type and amount of the reductant present (dithiothreitol, glutathione); (4) behavior of lipobeads with disulfide cross-linked hydrogel cores in the presence of reducing agents; the “exploding” lipobeads were observed at physiological pH. Understanding in details these key properties of the lipobead substructures sheds light on how to develop the so-called bioscopic anticancer chemotherapy with superior tumor response and minimum side-effects even at a greater drug loading concentrations, facilitates their preparation, decreases technological expenses on lipobeads scaled production.

Nuances of lipobeads as a bioscopic drug delivery system

ACS Spring Meeting 2021

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