Isabel Ortiz de Solorzano
Universidad de Zaragoza
Isabel Ortiz de Solórzano García graduated as Chemical Engineer in 2014 and achieved her Master Degree in Chemical Engineering one year after in the Univerisity of Zaragoza. During that year, she started her life as researcher working in the Nanostructured Films and Particles group (NFP) from the same University. Her investigation is based on the synthesis and characterization of hybrid nanomaterials combining inorganic and polymeric micro- and nanoparticles for biomedical applications. This work has been continued during the last two years as part of her PhD thesis funded by the Spanish Goverment with an FPU grant
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
