Polymeric nanoparticles (NPs) are very promising “smart carriers” for the future of nanomedicine. The main advantages of polymeric NPs manufactured by self-assembly are: high control of shape and size, high stability and significant increase of the solubility of poorly soluble drugs. Particle morphology can condition cytotoxicity, circulation time in blood, release of drug and removal of NPs from the body and thus improve the therapeutic efficacy. In turn, assembly can be guided by the choice of the environment. In this work, a protocol was developed for the synthesis and characterization of self-assembled polymeric NPs. We selected amphiphilic block copolymers of polyethylene oxide (PEO) and polylactic acid (PLA), two polymers already approved by the US Food and Drugs Administration (FDA) for medical use. The synthesis of the poly (lactic acid block) on a block of poly (ethylene oxide) has been carried out, by means of ROP (Ring Opening Polymerization) using a completely metal-free synthesis, catalyzed by 1,5-diazabiciclo[5.4.0]undec-5-ene (DBU), in order to avoid any problems of poor biocompatibility or allergenicity. The compositional characterization was carried out by solution Nuclear Magnetic Resonance (NMR) and calorimetric properties have been studied by Differential Scanning Calorimetry (DSC). After polymerizing a great variety of PLA chains of different length (PEO113-b-PLAx- with x ranging from 30 to 1359), nanoparticles were assembled from different organic solvents: dimethylformamide (DMF), acetone, tetrahydrofuran (THF) and dioxane, using the technique of nanoprecipitation. NPs were then purified by dialysis and analyzed by Dynamic Light Scattering (DLS), obtaining for each sample a mean hydrodynamic diameter value and a value of dispersion diameters. Particle diameter ranged from 40 to 800 nm, with many of the polymers presenting different values as a function of the starting solvent. A plot of all samples in terms of the DLS variables displayed several clusters, ideally associated to different morphologies. To verify the corresponding shapes, and then transform the plot into a morphological map that is able to guide the selection of the most promising nanocarriers for medical applications, Cryogenic Trasmission Electron Microscopy (cryo-TEM) investigation was necessary. Specificly we mapped the region of simple micelles (low diameter, low PDI) the region of polymersomes was mapped as well. The cytotoxicity tests were performed on all samples and only the largest nanoparticles reduced cell viability. Additional experiments of uptake and release of drugs were carried out, also through ad hoc assemblies in solvent mixtures that optimize the solubility of the drugs without affecting the morphology of “nanocarriers”.
(2017). Autoassemblaggio di copolimeri a blocchi anfifilici da buoni solventi: verso una mappa morfologica predittiva per la scelta del sistema di trasporto dei farmaci. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2017).
|Data di pubblicazione:||14-dic-2017|
|Titolo:||Autoassemblaggio di copolimeri a blocchi anfifilici da buoni solventi: verso una mappa morfologica predittiva per la scelta del sistema di trasporto dei farmaci|
|Settore Scientifico Disciplinare:||CHIM/04 - CHIMICA INDUSTRIALE|
|Corso di dottorato:||NANOSTRUTTURE E NANOTECNOLOGIE - 33R|
|Citazione:||(2017). Autoassemblaggio di copolimeri a blocchi anfifilici da buoni solventi: verso una mappa morfologica predittiva per la scelta del sistema di trasporto dei farmaci. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2017).|
|Parole Chiave (Inglese):||Copolymers; Self-Assembly; Solvents; Map; nanomedicine|
|Appare nelle tipologie:||07 - Tesi di dottorato Bicocca post 2009|