Histopathological analysis of zebrafish after introduction of non-biodegradable polyelectrolyte microcapsules into the circulatory system

Abstract

Polyelectrolyte microcapsules are among the most promising carriers of various sensing substances for their application inside the bloodstream of vertebrates. The long-term effects of biodegradable microcapsules in mammals are relatively well studied, but this is not the case for non-biodegradable microcapsules, which may be even more generally applicable for physiological measurements. In the current study, we introduced non-biodegradable polyelectrolyte microcapsules coated with polyethylene glycol (PMs-PEG) into the circulatory system of zebrafish to assess their long-term effects on fish internal organs with histopathologic analysis. Implantation of PMs-PEG was not associated with the formation of microclots or thrombi in thin capillaries; thus, the applied microcapsules had a low aggregation capacity. The progression of the immune response to the implant depended on the time and the abundance of microparticles in the tissues. We showed that inflammation originated from recognition and internalization of PMs-PEG by phagocytes. These microcapsule-filled immune cells have been found to migrate through the intestinal wall into the lumen, demonstrating a possible mechanism for partial microparticle elimination from fish. The observed tissue immune response to PMs-PEG was local, without a systemic effect on the fish morphology. The most pronounced chronic severe inflammatory reaction was observed near the injection site in renal parenchyma and within the abdominal cavity since PMs-PEG were administered with kidney injection. Blood clots and granulomatosis were noted at the injection site but were not found in the kidneys outside the injection site. Single microcapsules brought by blood into distal organs did not have a noticeable effect on the surrounding tissues. The severity of noted pathologies of the gills was insufficient to affect respiration. No statistically significant alterations in hepatic morphology were revealed after PMs-PEG introduction into fish body. Overall, our data demonstrate that despite they are immunogenic, non-biodegradable PMs-PEG have low potential to cause systemic effects if applied in the minimal amount necessary for detection of fluorescent signal from the microcapsules.

Durability of Implanted Low-Density Polyacrylamide Hydrogel Used as a Scaffold for Microencapsulated Molecular Probes inside Small Fish

“…We also showed the sensitivity of the developed sensors to metabolic acidosis in fish tissues provoked by increased environmental CO 2 during this period. Previously, we demonstrated that free polymeric microcapsules with polyethylene glycol coating are recognized by the immune system after hours and cause chronic inflammation for weeks [ 50 ]. Therefore, the obtained result demonstrates the increase in the operating time of implanted optical sensors based on polyacrylamide hydrogel up to days and confirms that amorphous PAAH delays the immune response of incorporated microparticles.…”

PEGDA microencapsulated allogeneic islets reverse canine diabetes without immunosuppression

“…PEG has long been utilized to improve the biocompatibility profile of other encapsulating compounds such as alginate [ 39 , 40 ]. In fact, the practice continues today with the combination of PEG with other encapsulants to obtain the desired physical features such as durability while improving the biocompatibility [ 41 , 42 ]. Specific to islets, PEG has been used with laborious methods that assemble individual layers of streptavidin and biotin-PEG conjugates to coat single islets [ 43 ].…”

Polyelectrolyte Multilayered Capsules as Biomedical Tools

“…In recent years, the use of calcium carbonate particles as templates has gained relevance. This requires the use of ethylene-diamine-tetracetic acid for ensuring the template dissolution [29,31]. It is worth mentioning that the preparation of PEMUCs using sacrificial colloidal particles as templates is not recommended for specific application because the obtained capsules can retain some toxic residues from the templates (dirty capsules), or solvent traces.…”

“…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]. Thus, the use of near infrared radiation allows triggering the release of doxorubicin from multilayers formed with poly(Llysine), bovine serum albumin, and a thermoresponsive gelatin hydrogel in which gold nanoparticles were embedded [212].…”

“…This allows the use of PEMUCs for loading in a protected environment and for delivery of a broad range of substances, e.g., inorganic nanoparticles, carbon nanotubes, antibodies, dyes, quantum dots, antitumoral drugs, proteins, or nucleic acids [19][20][21][22][23][24][25][26], which contributes to the enhanced bioavailability and solubility of active compounds [27,28]. This has stimulated the exploitation of polyelectrolyte multilayered capsules as cargo platforms in several biomedical applications inside the bloodstream [29][30][31]. Furthermore, these micro-/nanocontainers offer a very interesting capacity for controlled stimulus-sensitive release of the encapsulated functional components in response to specific external physical (ultrasound, magnetic field, laser pulse, or optical radiation), chemical (pH, ionic strength, or polarity of the environment), or biochemical (receptors or target cells) stimuli [32][33][34][35][36].…”