The Acute Immune Responses of the Common Carp Cyprinus carpio to PLGA Microparticles-The Interactions of a Teleost Fish with a Foreign Material.

Ruth Montero,Roman Kuchta,Astrid Sibylle Holzer,Jakub Vysloužil,Bernd Köllner,Tomáš Korytář,Peter Podhorec,Justin Tze Ho Chan

doi:10.3390/biom12020326

Abstract

Poly lactic-co-glycolic acid (PLGA) particles safely and effectively deliver pharmaceutical ingredients, with many applications approved for clinical use in humans. In fishes, PLGA particles are being considered as carriers of therapeutic drugs and vaccine antigens. However, existing studies focus mainly on vaccine antigens, the endpoint immune responses to these (e.g., improved antibody titres), without deeper understanding of whether fishes react to the carrier. To test whether or not PLGA are recognized by or interact at all with the immune system of a teleost fish, we prepared, characterized and injected PLGA microparticles intraperitoneally into common carp. The influx, phenotype of inflammatory leukocytes, and their capacity to produce reactive oxygen species and phagocytose PLGA microparticles were tested by flow cytometry, qPCR, and microscopy. PLGA microparticles were indeed recognized. However, they induced only transient recruitment of inflammatory leukocytes that was resolved 4 days later whereas only the smallest µm-sized particles were phagocytosed. The overall response resembled that described in mammals against foreign materials. Given the similarities between our findings and those described in mammals, PLGA particles can be adapted to play a dual role as both antigen and drug carriers in fishes, depending on the administered dose and their design.

Highlights

There is not enough evidence of how it interacts with the immune system and whether it is a suitable carrier for applications such as drug and vaccine antigen delivery—only the latter benefits from interaction with leukocytes and the immune system
From mammalian studies, we know that poly lacticco-glycolic acid (PLGA) particles alone activate human dendritic cells [28,29], but that they can be inert or at least not cause long-term side effects [13]
Based on demonstrated safety and efficacy in other animals, PLGA particles are being translated for therapeutic applications in many fish species

Summary

Introduction

Whether it is in human patients, laboratory animal models, or reared fishes, carriers offer protection, and timed release of drugs and vaccine antigens in order to produce a desired effect in the host. Biocompatible and biodegradable poly lacticco-glycolic acid (PLGA) particles have been tested for delivery of therapies targeting diseases such as type 2 diabetes and prostate cancer [1], whereas research is ongoing in the application of PLGA particles as vaccine antigen carriers [2,3].

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Results

Conclusion