Synthesis, characterization and applications of novel macromonomer-based biodegradable nanoparticles

Among the huge number of drug-containing polymer formulations proposed in the literature for drug delivery applications, only few of them reached the market. First generation medicines in which polymer are involved, including pills and mechanical devices, are well established while the same is not true for a second generation of carriers where the polymers are expected to play an active role, increasing the drug beneficial effects. In fact, while hundreds of publications address to the opportunities opened by targeted drug delivery, the only formulations reached the market were accepted mainly for their reduced toxicity profile. There is still a lack of optimization in this field since further studies aimed to assess and investigate problems such as biocompatibility, biodegradation and biodistribution are required. In this work, a new material library based on different functionalized polyesters has been developed responding to criteria as effectiveness and low cost. Such biodegradable polyesters (PLA, PLGA, PCL) show faster degradation rate compared to the formulation proposed in the literature; other peculiar characteristics of the library are the synthetic process which avoids the use of organic solvents, a tunable degradation time as well as easy adjustable features as size, surface charge and PEGylation. The library has been optimized through the continuous feedback obtained from in vitro and in vivo experiments, assessing the biocompatibility at cellular level, biodegradation, the internalization in different cell lines, and, finally, a proof of effectiveness as carriers for drug delivery

Il presente lavoro di tesi si colloca nell’ambito del “drug delivery”, più in particolare nella sintesi di nanoparticelle di dimensione nanomertriche finalizzate al rilascio controllato di farmaci. Ai fini di un uso all’interno del corpo umano queste devono presentare particolari caratteristiche di biocompatibilità e biodegradabilità. Pochi dei polimeri comunemente studiati in letteratura presentano tali caratteristiche per cui ci si è concentrati sulla sintesi di un nuovo monomero, in particolare una serie di macromonomeri basati su poliesteri che presentano le caratteristiche suddette. Tali macromonomeri sono stati sintetizzati via ROP ottenendo così una serie di molecole biodegradabili e in grado di polimerizzare per via radicalica, in particolare in emulsione, dando delle nanoparticelle di polimero a basso grado di polimerizzazione con le caratteristiche richieste. È stata quindi sviluppata una libreria di nanoparticelle testata in ambito biologico e ottimizzata tramite un continuo feedback ottenuto da esperimenti in vitro e in vivo.