PLGA Nanoparticles Grafted with Hyaluronic Acid to Improve Site-Specificity and Drug Dose Delivery in Osteoarthritis Nanotherapy
Luana Zerrillo,
Maria Rosa Gigliobianco,
Domenico D’Atri,
Joao Pedro Garcia,
Fabio Baldazzi,
Yanto Ridwan,
Gastón Fuentes,
Alan Chan,
Laura B. Creemers,
Roberta Censi,
Piera Di Martino,
Luis J. Cruz
Affiliations
Luana Zerrillo
Translational Nanobiomaterials and Imaging (TNI) Group, Department of Radiology, Leiden University Medical Centrum, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Maria Rosa Gigliobianco
Percuros B.V., Zernikedreef 8, 2333CL Leiden, The Netherlands
Domenico D’Atri
Department of Biotechnology and Food Engineering, Technion Israel Institute of Technology, Haifa 3200, Israel
Joao Pedro Garcia
Department of Orthopedics, Utrecht Medical Center, Heidelberglaan 100, 3584CX Utrecht, The Netherlands
Fabio Baldazzi
Translational Nanobiomaterials and Imaging (TNI) Group, Department of Radiology, Leiden University Medical Centrum, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Yanto Ridwan
Department of Radiology & Nuclear Medicine and Department of Molecular Genetics, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
Gastón Fuentes
Translational Nanobiomaterials and Imaging (TNI) Group, Department of Radiology, Leiden University Medical Centrum, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Alan Chan
Percuros B.V., Zernikedreef 8, 2333CL Leiden, The Netherlands
Laura B. Creemers
Department of Orthopedics, Utrecht Medical Center, Heidelberglaan 100, 3584CX Utrecht, The Netherlands
Roberta Censi
School of Pharmacy, University of Camerino, Via Madonna delle Carceri 9, 62032 Macerata, Italy
Piera Di Martino
Department of Pharmacy, Università “G. d’Annunzio” di Chieti e Pescara, Via dei Vestini 1, 66100 Chieti, Italy
Luis J. Cruz
Translational Nanobiomaterials and Imaging (TNI) Group, Department of Radiology, Leiden University Medical Centrum, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Nanoparticles (NPs) have a tremendous potential in medicinal applications, and recent studies have pushed the boundaries in nanotherapy, including in osteoarthritis treatments. The aim of this study was to develop new poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) surfaces decorated with hyaluronic acid (HA) to enhance targeted drug specificity to the osteoarthritic knee joint. HA was selected since it binds to specific receptors expressed in many cells, such as the cluster determinant 44 (CD44), a major receptor of chondrocytes, and because of its function in the synovial fluid (SF), such as maintenance of high fluid viscosity. The PLGA polymer was grafted to sodium hyaluronate using dimethoxy-PEG (PLGA-HA) and compared with control PLGA NPs (not grafted). NPs were characterized by 1H-NMR and IR spectroscopy. Then, near-infrared (NIR) dye and gold (20 nm) were encapsulated in the formulated NPs and used to access NPs’ performance in in vitro, in vivo, and ex vivo experiments. To test the NPs’ CD44 receptor specificity, an antibody assay was performed. All NPs presented a size in the range viable for cell-uptake, no cytotoxicity to chondrocytes was registered. Although all the NPs had a high capacity to be absorbed by the cells, PLGA-HA NPs showed significantly higher affinity towards the chondrocytic C28/I2 cell line. In conclusion, PLGA NPs grafted to sodium hyaluronate showed increased binding to cartilage cells and tissue and enhanced accumulation at the target site. Thus, this study presents a safe drug-delivery system with improved receptor specificity, which may represent an advantageous alternative to current nanotherapies.
