In this work PEGylated polyester-based nanoparticles (NPs) for drug delivery applications were synthetized through emulsion free radical polymerization. These NPs are produced starting from functionalized macromonomers whose average chain length can be tuned in a controlled way. Since the degradation of these NPs occurs through the hydrolysis of side chains, by tuning their length it is possible to obtain NPs with a controllable degradation time, comparable to data obtained with NPs internalized into cells. The long-term colloidal stability of these NPs in isotonic environment has been assessed through dynamic light scattering measurements and their degradation rate in cell medium has been proved to be fast and controllable. The NP behavior in gastric and intestinal solution was also studied.

Polymeric nanoparticles (NPs) are highly engineered nanoemulsions with applications in several fields. The control over NP surface chemistry, size (Dn), and molecular weight (MW) of the polymer they are made up of plays a paramount role in the optimization of their end-use performance. In this work, the theoretical basis to decouple the dependence between the NP Dn and MW has been presented, and an operative way has been demonstrated via ab initio reversible addition−fragmentation chain transfer (RAFT) emulsion polymerization (AIREP), a "living" heterogeneous process that adopts RAFT macro-surfmers: macromolecular chain transfer agents (CTA) produced via RAFT polymerization of amphiliphic monomers, such as surfmers. The possibility of obtaining the desired length of the lipophilic block or the length of the whole block copolymer and the NP Dn by choosing the correct length of the RAFT macro-surfmer has been assessed. It has been discovered that a wide range of Dn and MW can be achieved, but not very big NPs with very low copolymer MW; this limit is consistent with the physical and geometric constraints of the system.

Positively charged polymers have increased in importance in the last years because of the possibility of being used in many different applications, from gene delivery to polymer flooding applications and as flocculants in wastewater treatment. In all cases, the possibility of obtaining biodegradable colloidal products leads to great advantages. In this work, positively charged nanoparticles (NPs) have been produced via free radical emulsion polymerization (FREP). This synthetic route was selected since it is widely used in industry and it facilitates large scale production along with control of some key features of the final NPs such as their size, surface charge, and particle size distribution dispersity. NP synthesis was carried out by a four-step process: the synthesis of biodegradable esterbased macromonomers obtained through the ring-opening polymerization of the ε-caprolactone, the reaction among the obtained macromonomer and succinic anhydride, the final condensation with choline chloride to obtain the positively charged macromonomer, and the FREP polymerization of the produced macromonomer. The effects of reaction conditions on NP characteristics were studied, and the tunable behavior of the obtained charged NPs has been proven, also in terms of degradation time.

An optimal drug delivery system should be characterized by biocompatibility, biodegradability, high drug loading and favorable drug release profile. To achieve this goal a hydrazone linked doxorubicin-poly(lactic acid) prodrug (PLA-DOX) was synthesized by the functionalization of a short polymer chain produced by ring opening polymerization. The hydrophobic prodrug generated in this way was nanoprecipitated using a block copolymer to form polymeric nanoparticles (NPs) with a quantitative loading efficiency and a high and tunable drug loading. The effects of the concentration of the PLA-DOX prodrug and surfactant were studied by dynamic light scattering showing a range of NP size between 50 and 90 nm and monodispersed size distributions with polydispersity indexes lower then 0.27 up to a maximum DOX concentration of 27% w/w. The release profile of DOX from these NPs, tested at different pH conditions, showed a higher release rate in acidic conditions, consistent with the nature of the hydrazone bond which was used to conjugate the drug to the polymer. In vitro cytotoxicity studies performed on BV2 microglia-like cell line highlighted a specific cytotoxic effect of these NPs suggesting the maintenance of the drug efficacy and a modified release profile upon encapsulation of DOX in the NPs.

In this work, ring‐opening polymerization and reversible addition‐fragmentation chain transfer polymerization (RAFT) have been employed for the production of block copolymers where the backbone is brushed with poly(ethylene glycol) (PEG) and polyester chains. Because of their amphiphilic properties, they are able to self‐assemble in water, forming micelles. Molecular dynamics simulations have been accomplished to study the behavior of the copolymer single chain in water, and the self‐assembly properties have been characterized and correlated to the copolymer structure in terms of critical micellar concentration and particle size. As a proof of their flexibility, these materials have been employed for the production of polymer–lipid hybrid nanoparticles with tunable dimensions (from 120 to 260 nm) adopted for the controlled release of anticancer compounds (paclitaxel and curcumin). © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43084.