Dual Transport of Active Substances with a Layer‐by‐Layer‐Based Drug Delivery System to Terminate Inflammatory Processes

Abstract

Conventional therapies for chronic inflammation with high dose application of active agents are often accompanied with severe side effects so that other therapeutical strategies shall be developed to be less physically demanding but still highly efficient. Locally applied Layer‐by‐Layer (LbL) microcarriers transporting a low, but efficient dosage of active agents directly into the inflamed tissue offer a gentle therapy option. Here, the inhibition of highly degradative enzyme human neutrophile elastase (HNE) is adressed, which is produced and secreted by neutrophile granulocytes (PMNs) in the progress of inflammation. The protected transport and release of its natural inhibitor α1‐antitrypsin (AT) as a constituent of the microcarrier's biopolymer multilayer allows for an efficient inhibition of extra‐ and intracellular elastase. The HOCl scavenger molecule cefoperazone, which preserves AT activity, as an additional multilayer constituent induces a much higher efficacy of the inhibitor. The successful assembly of both agents in different layers of the multilayer and the subsequent HNE inhibition in PMNs is investigated. The parallel application of cefoperazone leads to an enhanced inhibitory effect even with reduced AT amount and reduced carrier:cell ratio. It is demonstrated that the modular assembly strategy of LbL carriers allows for efficient synergistic effect of active agents in inflammatory process.

The Metabolic Response of Various Cell Lines to Microtubule-Driven Uptake of Lipid- and Polymer-Coated Layer-by-Layer Microcarriers

“…LbL microcarriers consisted of a multilayer of PAH (PAH-RITC) and PSS as inner and PRM and DXS as biopolymer outer part ( Figure 1 ). Both polymer pairs (PAH/PSS, PRM/DXS) are built up as a regular step-by-step multilayer as previous zeta potential measurements reveal [ 32 , 33 ]. As a final surface coverage, the carriers either terminated with a negatively charged polymer layer (DXS, named as polymer microcarriers, Figure 1 a) or with a SLB (hereafter referred to as SLB microcarriers, Figure 1 b).…”

Polyelectrolyte Multilayered Capsules as Biomedical Tools

“…Laser light activation can be used for inducing a local heating of the capsule, which triggers the release of the encapsulated compounds [207]. This requires introducing optically active components in the LbL shell, which is commonly achieved by embedding metal nanoparticles, playing a very important role in intracellular release [208], multi-substance delivery [209], or endosomal escape [210]. The mechanism of the laser light activation relies on the heating of the particles by light irradiation, which can induce the rupture of the shell or the modification of its permeability [31,211].…”

Nanoparticles in Polyelectrolyte Multilayer Layer-by-Layer (LbL) Films and Capsules—Key Enabling Components of Hybrid Coatings

“…Applied to polyelectrolyte multilayer films and capsules, volume (global) heat is used to encapsulate molecules, but the local heating is used for the release from capsules [178]. Light-induced heat generation can be employed for opening of capsule shells and release of encapsulated molecules [28,179], which is particularly interesting for intracellular release, [180] multi-substance delivery [181] or endosomal escape [182]. This is because nanoparticles incorporated into the shells of capsules have been shown to control remotely by laser light [183] treatment of capsule shells modified by metal nanoparticles, heat is generated around NP causing a complete rupture or a permeability change of the capsule walls [184,185].…”

“…Release of a model drug (doxycycline) was demonstrated by manipulating the permeability of microcapsules without causing a significant damage to the capsule shells. This was achieved as a result of a long-term treatment of the capsules by low frequency [181] alternating magnetic fields as a non-cytotoxic intracellular trigger [210].…”