Tailoring calcium phosphate nanoparticles for medical applications: a functional by design approach

Abstract

Medicine is a field in continuous expansion as the molecular and genetic causes of pathologies are discovered and new therapeutic treatments are developed. On the viewpoint of material science there is an ever-growing demand of new advanced materials such as therapeutic agents, tissues substitutes, regenerative agents, and as component of biomedical devices. The materials must have at the same time excellent properties, minimal costs, and do not have side reactions with the biological environment. For this reason there is a high interest in nanomaterials for medicine, since these advanced materials promise to have all of the above-mentioned features. However, the development of nanomaterials designed to have specific functions is a complex process. Nano- objects cannot be processed or controlled directly, and their behavior and properties fall in between the domain of chemistry and physics. A lot of research effort is devoted on understating and controlling nanomaterials characteristics in order to fulfil the requirements of nanomedicine. The research activity reported in this Ph. D. Thesis was focused on the development of new calcium phosphate nanomaterials for medical application. The research was carried out at the Institute of Science and Technology for Ceramics, belonging to the National Research Council of Italy (ISTEC C.N.R.) under the supervision of Dr. Michele Iafisco. The materials presented in this Ph. D. Thesis possess different physicochemical properties and are employed in very different applications, but were all developed with the “functional by design” approach. This approach, proposed for the first time in this Ph. D. Thesis, is based on the concept that the nanomaterial is knowingly designed and tailored to fulfil a specific function. The functional by design approach was achieved through a bottom-up preparation of nanoparticles employing organic and inorganic templates to tailor nanoparticles physicochemical properties. The first part of the Ph. D. work was dedicated to the design of calcium phosphate nanoparticles for cardiac drug delivery. Nanoparticles were designed to encapsulate a biomolecular drug and to deliver it to the cardiac district for treating cardiovascular diseases. Furthermore, the nanoparticles design allowed drug delivery through the inhalation route, which proved to be more effective and pain-free than the conventional parenteral administration routes. The second part of the Ph. D. work was focused on the design of calcium phosphate nanoparticles for enamel remineralization and dentin desensitization. The nanoparticles were tailored to quickly dissolve in the mouth environment and to form a new fluorine-doped mineral phase onto enamel and dentine, thus restoring enamel resistance and occluding exposed dentinal tubules. The third part of this Ph. D. work was devoted to basic research on calcium phosphate nanoparticles formation, with the aim to deepen the knowledge on nanoparticles crystallization and growth in presence of template molecules. Calcium phosphate nanoparticles nucleation, growth and maturation in presence of one or more regulator molecules has been thoroughly studied in order to understand the effect such regulators.