Development of UV-based polymerization techniques for the production of drug delivery devices

Production of particles with dimension in the submicron scale underwent a significant increase in the last decades. The idea to exploit these devices to actively target a wide range of applications drove many important efforts in the development of such particles. In particular, the possibility to encapsulate and release active ingredients with desired rates, as well as to specifically target certain areas of the human body, is of huge importance in therapeutic treatments. Among the broad spectrum of micro and submicron particles, polymeric particles represent an extremely versatile class of devices. Their high biocompatibility and possibility to swell or degrade to enhance release once in contact with body fluid are particularly interesting in drug administration. This work was focused on the development of new techniques to produce structured polymeric particles in the micro and nano regions. Two rather different polymerization techniques were investigated and modified in order to pursue this goal: miniemulsion and aerosol polymerization. In both cases, polymerization triggering was achieved by UV light in presence of photo-initiator compounds and two reaction mechanisms were investigated: radical and cationic. Miniemulsion polymerization was studied as a case study of a well-known technique for production of polymeric particles. One major modification was applied to the standard experimental setup: polymerization was confined at the interface between dispersed and continuous phase, thus producing capsules with a polymeric shell and a liquid core. The product was characterized and the impact of process conditions on size and morphology of capsules was evaluated. In particular, ultrasound exposure time was used to design capsules size. After optimization of process parameters, an active ingredient was encapsulated. Its controlled release was evaluated in case of different polymeric shells. Differences were observed using different degrees of crosslinking in the polymeric material, thus showing the possibility to design release rate by varying the ratio between monomer and crosslinker. Aerosol polymerization was studied as a rather new technique for production of polymeric particles. It is a continuous process that does not require a liquid medium nor, usually, surfactants. For these reasons, it does not imply a cumbersome downstream work of purification. One major drawback of this technique is the challenging particles structuring process. In our work, phase separation was induced within aerosol droplets to obtain structured particles. Mixtures of ―good‖ and ―bad‖ solvents were used to carefully design solubility of the monomer and its oligomers in the sprayed solution. Thus, it was possible to obtain different porous particles morphologies simply by varying the ratio between the two solvents. Capsules structures were obtained using different approaches in cationic and radical mechanism. Chain transfer mechanism was applied in cationic polymerization by adding an alcohol in the sprayed solution, while the addition of a soft-maker was crucial for the production of polymeric shells in radical polymerization. In both cases, the goal was to delay gelation of the polymeric structure, thus providing more time for the structuring process. Once the particles morphology was designed, an active ingredient was encapsulated within different types of particles and its release was monitored. Molecular dynamic simulations were carried out to study the mechanisms that control the structuring process in aerosol cationic polymerization. Diffusion of the oligomer in the solvent mixture, as well as its interactions with the solvents, were calculated and the results confirmed the strong impact of solvent composition on the macromolecules transport parameters and, therefore, on their morphology.