Biodegradable Defined Shaped Printed Polymer Microcapsules for Drug Delivery.

This work describes the preparation and characterization of printed biodegradable polymer (polylactic acid) capsules made in two different shapes: pyramid and rectangular capsules about 1 and 11 µm in size. Obtained core-shell capsules are described in terms of their morphology, loading efficiency, cargo release profile, cell cytotoxicity, and cell uptake. Both types of capsules showed monodisperse size and shape distribution and were found to provide sufficient stability to encapsulate small water-soluble molecules and to retain them for several days and ability for intracellular delivery. Capsules of 1 µm size can be internalized by HeLa cells without causing any toxicity effect. Printed capsules show unique characteristics compared with other drug delivery systems such as a wide range of possible cargoes, triggered release mechanism, and highly controllable shape and size.

Alginate microbeads with internal microvoids for the sustained release of drugs.

The process of Ca2+ mediated gelation of alginate and the fabrication of nanoengineered polyelectrolyte capsules were combined for the preparation of alginate microbeads characterized by the presence of well-defined drug loaded microvoids in their volume. The obtained engineered alginate microbeads are described in terms of their morphology, loading efficiency and release characteristics. It was found that the generation of microvoids in the volume of alginate microbeads could be a promising approach for the creation of microstructured and biocompatible hydrogels, prospectively having highly tunable properties in terms of loading and releasing characteristics. In particular, it was found that the developed system was able to limit drug leakage during the gelation process and to control the initial burst release of small hydrophilic drug molecules, such as doxorubicin hydrochloride. Finally, the cytocompatibility of the developed microhydrogels was assessed on MCF-7 human breast cancer cells as well as their ability to sustain the release of the model drug during time.

Multicompartment Hydrogels for the Local Delivery of Chemotherapic Drugs.

Over 85% of human cancers are solid tumors. The effectiveness of anticancer therapy in solid tumors depends on adequate delivery of the therapeutic agent to tumor cells. Inadequate delivery would result in residual tumor cells, which in turn would lead to regrowth of tumors and possibly development of resistant cells. The most prominent option, for now, is the local delivery of chemotherapic drugs into the cavity resection of the tumor. However, the burst release of massive concentrations of the drugs usually boosts the side effects of chemotherapy. Aiming to block the burst release a new drug delivery system (DDS) for the local delivery of Doxorubicin (DOX) was designed and tested, combining different materials and techniques. Following a bottom-up approach, porous spherical calcium carbonate (CaCO3) microspheres, with high loading properties, were loaded with DOX and Layer by Layer (LbL) assembled by biocompatible and biodegradable polyelectrolytes, dextran sodium sulfate (DSS) and polyarginine (PARG). Then, a protocol for the fabrication of alginate (Alg) hydrogels associated with LbL coated drug loaded CaCO3 microspheres were developed by combining internal and external gelation. Therefore, injectable multicompartment hydrogels (MCH) for the local and sustained delivery of chemotherapeutic drugs, with the ability to block the burst release, were developed and characterized.

Encapsulated functionalized stereocomplex PLA particles: An effective system to support mucolytic enzymes.

In this work, the preparation of a novel enzyme carrier based on a polymer multicomponent system was assessed. Indeed, the design of the above system considered several issues that are the need of applying a biodegradable polymer carrier, characterized by a nanometric dimension, thus suitable to diffuse into the dense mucus structure, with functionalities capable of interacting/reacting with enzymes but resistant to enzymatic degradation. The particles were prepared from solutions containing equimolar amount of high-molecular-weight poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA) and by applying the nanoprecipitation method. Dynamic Light Scattering (DLS) measurements allowed to establish the optimal preparation conditions to obtain polymer particles characterized by diameters lower than 1 µm, which dimensions were confirmed by Field Emission Scanning Electron Microscope (FE-SEM) analysis. In order to produce surface functionalization, necessary for anchoring enzymes, the stereocomplexed particles, whose structuration was confirmed by Differential Scanning Calorimetry (DSC) measurements, underwent an amminolysis reaction by using a diamine as reactant. The treated particles were characterized by means of FE-SEM, Fourier-Transform Infrared Spectroscopy (FTIR), DLS and zeta potential measurements and their characteristics were compared with those of the neat PLLA/PDLA particles. The degree of functionalization turned out to depend on the applied conditions, it increasing by enhancing the reaction time. The activity of enzymes, i.e. papain and alginate lyase, anchored to the particles, was evaluated by Quartz Crystal Microbalance (QCM) and UV measurements. Moreover, with the aim at exploiting the material for an inhalation administration, a method to encapsulate the enzyme-particles systems was assessed. Conversely to free enzymes, the developed systems were found to be capable of diminishing the viscosity of two hydrogels, ad hoc prepared and based on the main constituents of the real mucus.