Design and fabrication of polymeric nanoengineered delivery systems for improved performance and controlled release

Drug delivery is an increasingly investigated field, aiming at distributing a therapeutic substance precisely to the area, tissue or cell where needed and consequently controlling its release, thus guaranteeing optimal efficiency. Besides, this targeted action can also bring significant advantages in other diverse sectors. The delivery systems designed and fabricated in this work were meant to overcome some of the issues related to current therapies for different illnesses. Specifically, polylactic acid (PLA) was exploited to produce nanoparticles which were functionalized and encapsulated in polyelectrolyte Layer-by-Layer (LbL) microcontainers to support mucolytic enzymes’ action, with the aim of overcoming thick mucus barriers in cystic fibrosis patients’ upper airways, and reducing their viscosity. Moreover, nanoparticles were also modified with cyclodextrins to carry small hydrophobic anti-inflammatory drugs. Alginate was used to produce multicompartment hydrogels containing LbL capsules loaded with a chemotherapeutic drug, to achieve a local prolonged delivery in solid tumour resection cavities. However, as a general consideration, these systems can act as delivery carriers for a wide variety of drugs and can be exploited for various purposes, also other than the delivery of therapeuticals, which still remains the main focus of this thesis. An example of the engineering point of view is represented by LbL capsules, which can carry nanoparticles as well as small water-soluble chemotherapeutic drugs with slight or no modification of the production procedure, as above mentioned. Another example, showing strongly different fields of application of the same system, is constituted by cyclodextrins-modified PLA nanoparticles, which demonstrated the ability to complex with an anti-inflammatory drug, namely ketoprofen, as well as with an industrial pollutant, namely alizarin red s, without being modified. Finally, PLA was also used in a novel approach to obtain specific geometries of microchambers and microcapsules for the retention of small hydrophilic molecules. In this case, the great potential relies on the fabrication technique used for these carriers. Specifically, the use of PDMS molds offers a reproducible fabrication of differently sized and shaped bottomless microchambers and capsules. Once the stamps are covered with the chosen polymer but still open, they can be loaded with various techniques, from the in-liquid to the dry powder loading. This allows to fill those carriers with smaller or bigger molecules, being water soluble or insoluble, potentially using almost all the available inner volume of the carrier, which is a reversal of the traditional carrier filling in drug delivery. This production method also pavents the way for industrial scalability of drug delivery systems, potentially overcoming some of the biggest obstacles to this modern way of re-thinking pharmaceutical dosages. The overall findings of this thesis support the efforts in making drug delivery carriers a greatly promising tool for pharmaceutical therapies and dosages. Specifically, biopolymers can allow a great advance in the fields of drug delivery and materials engineering.