In vivo imaging and local persistance of polymeric micro- and nanomaterials labelled with the near-infrared dye IR820

INTRODUCTIONIn biomedical applications, the use of micro- and nanomaterials as drug delivery carriers can enhance the efficiency of treatments by avoiding side effects1. The binding of a dye to a drug or to a drug-carrier has... [ view full abstract ]

INTRODUCTION

In biomedical applications, the use of micro- and nanomaterials as drug delivery carriers can enhance the efficiency of treatments by avoiding side effects¹. The binding of a dye to a drug or to a drug-carrier has opened a wide range of possibilities for an efficient drug biodistribution tracking². Optical imaging techniques are effective approaches to demonstrate drug biodistribution in vivo using non-invasive real-time methodologies.^3,4 The aim of this work is the development of novel polymeric micro- and nanomaterials of different sizes fluorescently labelled with the NIR dye IR820 to track their in vivo biodistribution after intramuscular and subcutaneous administration.

EXPERIMENTAL METHODS

Materials synthesis

Different micro and nanoparticles based on PLGA (poly(lactic-co-glycolic acid))and on PNIPAm (Poly(N-isopropylacrylamide)) have been chemically modified to include the NIR dye IR820 by using carbodiimide coupling. PNIPAM-IR820 microgels were obtained by conventional batch synthesis and PNIPAM-IR820 microparticles (MPs) were prepared by microfluidic LED polymerization.

In vitro assays

The cytotoxicity of the labelled materials was studied at three essential levels: cell metabolism, cell cycle, both on five different cell types; and endotoxin content.

In vivo studies

In vivo imaging studies were performed with five-to-eight-week-old female BALB/c nu/nu mice with the IVIS® Lumina Xenogen equipment. A complete histopathologic study was carried out.

RESULTS AND DISCUSSION

We will describe the synthesis and characterization of the resulting fluorescently labelled micro- and nanoparticles. The resulting materials showed sizes ranging from 120 nm to 410 µm. The in vitro biological studies revealed a high biocompatibility of the developed materials at doses up to 1 mg/mL on five different cell lines as well as the absence of potentially harmful bacterial contamination. The in vivo imaging system (IVIS) analysis performed in nude mice allowed the long-term tracing of materials biodistribution after intramuscular and subcutaneous administration showing their local persistence and the biocompatibility after histopathological studies.

REFERENCES

1. Korsmeyer, R. et al. Reg. Biomaterials, 3(2), 143–147, 2016

2. J.O Escobedo et al. Curr. Opin. Chem. Biol. 14:64-70, 2010

3. A.R Patel et al. Pherm. Res. 31:3073-84, 2014

4. C.E. Badr et al. Trends Biotechnol. 29:624-633, 2011