Development of LbL biopolymer capsules as a delivery system for the multilayer-assembled anti-inflammatory substance α1-antitrypsin

The Application of LbL-Microcarriers for the Treatment of Chronic Inflammation: Monitoring the Impact of LbL-Microcarriers on Cell Viability

“…Another important issue that needs to be considered is the microcarrier's impact on the viability of inflammatory cells, which is emphasized in this work. In previous studies, our group could already show an only marginal influence of LbL‐microcarriers on the release of pro‐inflammatory cytokines (tumor necrosis factor α and interleukin 1β) by macrophages . These observations are in accordance with in vivo studies from De Koker et al, who demonstrated only a moderate immune reaction of LbL‐microcapsules after subcutaneous injection into mice .…”

“…In previous studies, our group could already show an only marginal influence of LbLmicrocarriers on the release of pro-inflammatory cytokines (tumor necrosis factor a and interleukin 1b) by macrophages. [25,27] These observations are in accordance with in vivo studies from De Koker et al, who demonstrated only a moderate immune reaction of LbLmicrocapsules after subcutaneous injection into mice. [28] However, for the intended biomedical application, the polyelectrolyte-multilayer material, as well as the core material of the LbL-microcarriers themselves, may have a serious impact on cell viability.…”

“…During PEMC fabrication, Fluo‐4 AM (Invitrogen, UK) was used for detection of the remaining calcium ions as previously described . Briefly, 50 μg Fluo‐4 AM were dissolved in 10 μl DMSO and 990 μl 0.1 M NaCl.…”

“…This is possible since even large objects in micrometer dimension will be incorporated by those professional phagocytes; (ii) A microcarrier‐mediated (further) induction of PMN's necrosis and even apoptosis has to be strongly avoided to prevent secondary proinflammatory signaling of macrophages. To fulfil those demands, our group recently presented a very efficient approach in the parallel, that is extracellular as well as intracellular, inhibition of the human neutrophil elastase (HNE) by LbL‐microcarrier delivered α 1 ‐antitrypsin (AT) . HNE is a highly proteolytic enzyme, which is stored in azurophilic granules of PMNs, released in the course of inflammation and subsequently responsible for the destruction of the affected tissue .…”

“…To fulfil those demands, our group recently presented a very efficient approach in the parallel, that is extracellular as well as intracellular, inhibition of the human neutrophil elastase (HNE) by LbL-microcarrier delivered a 1 -antitrypsin (AT). [24][25][26] HNE is a highly proteolytic enzyme, which is stored in azurophilic granules of PMNs, released in the course of inflammation and subsequently responsible for the destruction of the affected tissue. [20,21] Once AT-assembled microcarriers are phagocytosed by PMNs, AT has reached its targeted cell compartment, the phagolysosome, gets released during multilayer decomposition [26] and efficiently inhibit HNE directly at its place of origin.…”