The restenosis after percutaneous transluminal angioplasty (PTA) mainly involves the uncontrolled proliferation of smooth muscle cells (SMC) in blood vessel’s tunica media. The local delivery of hyperplasia inhibiting drugs could allow to reduce its occurrence. One of the possible approaches can consist in the release of drug loaded polymeric nanoparticles (NP) during the expansion of the balloon. This preliminary work aims to evaluate the feasibility of NP made of anti-oxidant grafted PLGAs (g- AA-PLGA) as potential novel drug carrier for restenosis prevention. Caffeic acid (CA) and resveratrol (RV) were grafted to PLGA (L/G ratio 50/50, Mw=20.4 KDa, Tg=47.1±0.5 °C) by a radical process [1, 2]. The materials were characterized by DSC, GPC and DPPH assay. NP were prepared by the solvent displacement method and characterized for hydrodynamic diameter (DH) and zeta potential () by DLS. NP cytotoxicity was evaluated by MTT assay. Cellular uptake and subsequent exocytosis was studied in macrophages, SMC and endothelial cells. The grafting procedure permitted to obtain polymers with good radical scavenging properties (DPPH inhibition at 1h of 90.0±0.4% for g-CA-PLGA and 27.0±0.8% for g-RV-PLGA) without a significant variation in Mw. Monodispersed NP with a DH lower than 200 nm and a of about -30 mV were prepared for all the polymers. MTT assays evidenced no signs of cytotoxicity in all the cellular models. In macrophages, no statistically differences were found among the uptake of all the types of NP. In endothelial cells, the uptake of g-CA-PLGA NP was significantly higher than the one of g-RV-PLGA and PLGA NP (two-way ANOVA: g-CA-PLGA vs PLGA p=0.028 and g-CA-PLGA vs g-RV-PLGA p=0.032). Moreover, g-RV-PLGA and PLGA NP were similarly taken up (p>0.05). In SMC, the uptake of g-CA-PLGA NP occurred faster compared to the other NP (one-way ANOVA: g-CA-PLGA vs PLGA p=0.002; g-CA-PLGA vs g-RV-PLGA p=0.004 and g-RV-PLGA vs PLGA p=0.984). The exocytosis of g-CA-PLGA NP occurred within 8 h and 48 h in macrophages and SMC, respectively. These data agreed with images obtained by fluorescence microscopy. The results on cellular uptake and exocytosis demonstrate that g-CA-PLGA NP may be a suitable carrier to locally administer drugs, in the prevention of restenosis following PTA. References  Cilurzo F, Puoci F, Selmin F, Iemma F, Minghetti P. Pyrogallic acid-PLGA conjugate as new biodegradable material suitable for final sterilization by irradiation. Polym. Adv. Technol., 22, 2201- 2205, 2011.  Selmin F, Puoci F, Parisi O.I, Franzè S, Musazzi U.M, Cilurzo F. Caffeic acid-PLGA conjugate to design drug delivery systems stable to sterilization. J. Funct. Biomater., 6, 1-13, 2015.
Anti-oxidant grafted PLGA nanomaterials for neointimal hyperplasia prevention: a feasibility study / G. Magri. ((Intervento presentato al convegno Advanced School in Nanomedicine tenutosi a Pula nel 2017.
|Titolo:||Anti-oxidant grafted PLGA nanomaterials for neointimal hyperplasia prevention: a feasibility study|
MAGRI, GIULIA (Primo) (Corresponding)
|Data di pubblicazione:||26-set-2017|
|Settore Scientifico Disciplinare:||Settore CHIM/09 - Farmaceutico Tecnologico Applicativo|
|Citazione:||Anti-oxidant grafted PLGA nanomaterials for neointimal hyperplasia prevention: a feasibility study / G. Magri. ((Intervento presentato al convegno Advanced School in Nanomedicine tenutosi a Pula nel 2017.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|