Understanding and utilizing the biomolecule/nanosystems interface: Soft materials and coatings for controlled drug release

Kapitel i bok, 2017

Combining biomolecules with materials used in medicine allows for local control of the biological response and can be used for modulating the host immune response, a major challenge in the efficacy of many medical devices. In Subchapter 3.1, we will review different methods used to attach biomolecules to materials, focusing on protein conjugation methods. We will begin by describing noncovalent immobilization strategies, including encapsulation within biomaterials and adsorption to material surfaces. We will then discuss strategies to covalently attach biomolecules to materials via the use of specific functional groups, thus enhancing the stability of the interaction. Finally, we will describe emerging methods to site specifically immobilize biomolecules to materials such that proteins are presented in an oriented manner, improving their overall functionality. Throughout the subchapter, we will emphasize the advantages and disadvantages of each technique, successes achieved, as well as the challenges remaining in this growing field.During last years, increasing development of nanoparticles as targeted drug delivery agents, has led to a wide amount of studies involving their characterization to the application as novel therapeutic agents. Hence, the nanoparticles interact with biological environments when they enter in the human body, and then proteins bind to the nanomaterial surface forming the protein corona. Protein corona has a great relevance in the interaction and function of the nanoparticle-drug conjugates. In fact, its characterization is one of the main challenges for nanoscience development. Herein, it is reviewed the main proteomic methods described for quantify and qualify the protein corona formed around nanoparticles to better understand the process of interaction with the biological media, and to decipher key parameters to control the effects of the protein corona.In Subchapter 3.3, the structure and working principles of coatings for controlled drug release in oral drug administration are presented. The release mechanisms, including diffusion, dissolution, osmotic pumping, and swelling are described. The soft materials used in the majority of controlled drug release formulations are natural and synthetic polymers. They are presented here and examples of specific polymers applied in controlled release formulations are provided. There is also a section containing characterization of soft materials using in situ electron microscopy for studying water transport through coatings at high-spatial resolution. The reason for this is that the detailed properties and release mechanisms of the controlled release depend on the material nanostructure. The in situ characterization gives access not only the information about the nanostructure but also the direct correlation between structure and properties on different length scales. Finally, an overview of the present major challenges and future possibilities concerning controlled drug release formulations is presented.Targeting cancer cells with functional nanoprobes possessing a targeting drug unit and an imaging moiety carries great potential for early detection, accurate diagnosis, and targeted therapy of various diseases. Given their nanoscopic dimensions, ultrasmall particles ( < 100nm) are in general well suited for interactions with the cells; however, the current challenge of the nanomedicine is to transform inorganic nanoparticles of metals (e.g., gold) or metal oxide (e.g., magnetite) into signal-generating vectors. Engineered nanostructures can act as vehicles for a large number of signaling centers and/or targeting units thereby offering unique opportunity to enhance the sensitivity by locally enhancing the density of signal groups. For this purpose, creation of surface groups enabling chemical attachment of antibodies or other targeting biomolecules are essential that will allow the delivery of therapeutic payloads to the diseased sites. Multimodal nanoprobes functionalized with different diagnostic and therapeutic options within a single nanoparticle followed by their functionalization with organic ligands and biomolecules can provide specific uptake and high sensitivity toward anatomical information. However, the vision of making clinical theranostics a routine clinical procedure is encumbered by limited stability of complex nanoparticles in biological milieu and lack of standardization of therapy response. Despite the widely acclaimed advantages of integrating diagnostic imaging, drug delivery, and therapeutic monitoring in a single nanotheranostic probe, the clinical utilization of engineered nanoprobes demands concerted efforts in the domains of nanoparticle and surface chemistry/charge, new chelator ligands, pharmaceutical technology, radioactive labeling of nanovectors, biokinetics, and pharmacodynamics of nanoprobes, and biological tests (cell tests and animal models).