Novel Fluorinated Poly (Lactic-Co-Glycolic acid) (PLGA) and Polyethylene Glycol (PEG) Nanoparticles for Monitoring and Imaging in Osteoarthritis.

Luana Zerrillo,Alan Chan,Candido G Da Silva,Weiqiang Dou,Mangala Srinivas,Federica Galli,Karthick Babu Sai Sankar Gupta,Piera Di Martino,Andor Veltien,Fons A.W.M Lefeber,Roberta Censi,Luis Cruz

doi:10.3390/pharmaceutics13020235

Abstract

Polymeric nanoparticles (NPs) find many uses in nanomedicine, from drug delivery to imaging. In this regard, poly (lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) particles are the most widely applied types of nano-systems due to their biocompatibility and biodegradability. Here we developed novel fluorinated polymeric NPs as vectors for multi-modal nanoprobes. This approach involved modifying polymeric NPs with trifluoroacetamide (TFA) and loading them with a near-infrared (NIR) dye for different imaging modalities, such as magnetic resonance imaging (MRI) and optical imaging. The PLGA-PEG-TFA NPs generated were characterized in vitro using the C28/I2 human chondrocyte cell line and in vivo in a mouse model of osteoarthritis (OA). The NPs were well absorbed, as confirmed by confocal microscopy, and were non-toxic to cells. To test the NPs as a drug delivery system for contrast agents of OA, the nanomaterial was administered via the intra-articular (IA) administration method. The dye-loaded NPs were injected in the knee joint and then visualized and tracked in vivo by fluorine-19 nuclear magnetic resonance and fluorescence imaging. Here, we describe the development of novel intrinsically fluorinated polymeric NPs modality that can be used in various molecular imaging techniques to visualize and track OA treatments and their potential use in clinical trials.

Highlights

Our novel PLGA-polyethylene glycol (PEG)-TFA copolymer was synthesized in three steps
The results indicate that the 19 F signal decreased gradually, suggesting that the PLGA-PEG-TFA NPs were successfully visualized
F-MRIIt was co-polymer, successfully namely visualized and traced in that allowed us to trace the NPs by 19 F-MRIIt was successfully visualized and traced in vitro, in vivo, and ex vivo by optical imaging and 19 F-magnetic resonance imaging (MRI) in an osteoarthritic knee joint mice model

Summary

Introduction

Almost 10% of the population suffers from symptomatic knee OA at the age of 60, a condition that leads to articular cartilage damage [1,2]. The cartilage is the main component of synovial joints and it is formed by chondrocytes. These cells assemble the extracellular matrix and they contribute greatly to hyaline cartilage regeneration. In knee joint OA, physiological changes are observed in the synovial membrane, cartilage, and bone structures. There are no definite pharmacological treatments for OA. There are no pharmacological treatments for the early stage, OA progression can be slowed by

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