Interaction, uptake, and processing of LbL-coated microcarriers by PMNs

摘要

Functionalized microcarriers or hollow capsules transporting active agents offer the opportunity for drug delivery inside cells. A promising application of these drug delivery systems is the direct transport as well as the release of immobilized antiinflammatory substances (AIS) into polymorphonuclear leukocytes (PMNs), which play a key role in the course of inflammatory processes. The intended delivery of AIS into the inflamed tissue could alleviate tissue destruction taking place during chronic inflammation, as well as facilitate the termination of these processes. In this study, the capability of functionalized CaCO_3 microcarriers as AIS transporter system targeted at PMNs is investigated. The time-dependent interaction of protamine sulfate and dextran sulfate multilayer-coated 5 μm ± 1 μm CaCO_3 carriers with PMNs, in comparison with the usage of SiO_2 carriers as monodisperse model system of defined sizes (1, 3, and 5 μm), reveals a sufficient carrier/cell interaction and uptake for coincubation periods between 2 and 24 h. Furthermore, the microcarriers are exposed to an environment simulating primary granule/phagosomal conditions after phagocytosis by means of PMN stimulation. The incubation of CaCO_3 microcarriers with cell supernatant demonstrates a partial multilayer decomposition (three to five layers) within 24 h, allowing the gradual release of AIS within the short PMN life span. This observation suggests a potential application for this drug delivery system inside immunologically active cells and may open the way to new alternatives in the treatment of chronic processes.