Nanotechnology and controlled drug delivery

Introduction
Nanotechnology advances in drug delivery deal with the development of synthetic nanometer sized targeting delivery systems for therapeutic agents. It exploits the improved properties of materials at the nanometer scale. At this scale, manmade structures match typical sizes of natural functional units in living organisms thus allowing them to interact with biomolecules. Major goals are the increase of drug availability and efficacy, control of immunogenicity, toxicity and bio-recognition also the overcoming of obstacles(e.g., air-blood barrier). Therapeutic systems in this class are up to a million times larger than classical drugs like aspirin. Their increased complexity however, gives these systems the unique power to tackle more challenging diseases. It can have multiple functions, a key is their ability to recognize specific molecules which can be located either on the membrane of target cells, or in specific compartments within the cell.

Why it is Important in Clinical Medicine
Nanomedicine has the potential to enable early detection and prevention, and to essentially improve diagnosis, treatment and follow-up of diseases (e.g., combination of diagnostic devices and therapeutics with a real benefit for patients). Nanomedicine is a very special area of nanotechnology, because: (I) it is an extremely large field ranging from in vivo and in vitro diagnostics to therapy including targeted delivery and regenerative medicine, (II) it interfaces nanomaterials with “living” human material and (III) it creates new tools and methods that impact significantly existing conservative practices.

Before and After Nanotechnology Revolution
As shown in Table, the drug delivery technologies in relation to the current nanotechnology revolution can be classified into three categories.

The current technology of fabrication and manufacturing of engineering materials at the nano/micro scale is advanced enough to develop nano/micro scale processes for producing products other than semiconductors. Imagine that the current soft gelatin capsules, which are in the centimeter scale, are manufactured at the nano/micro scale.

Development and Delivery
A challenging objective is the development of innovative specialties approaches for the design, synthesis and functionalization of modern nano-carriers for targeted delivery of protein/peptide (P/P) drugs via oral, pulmonary and nasal administration routes as well as the manufacturing of “smart” miniaturized drug delivery devices able to release a variety of drugs on demand.

Another challenge is the delivery of P/P drugs via alternative noninvasive administration routes. Currently, the majority of biopharmaceutics are delivered by injection. However, since some P/P drugs can be rapidly cleared from the body before achieving their therapeutic goal, patients have to undergo more frequent injections, to enhance the therapeutic effectiveness, which is inconvenient and painful. The above goals are expected to be achieved, through the development of targeted drug delivery systems that can be selectively delivered to specific areas in the human body. However, since drug characteristics differ substantially. the essential characteristics that identify the efficiency of the drug delivery system are highly complex. Thus, their development has to be pursued.

Current State of Development & Applications
The benefits promised by nanoscience and nanotechnology in making medicines more efficacious have been endlessly pronounced since the inception of the concept. Nevertheless, the field and its applications in drug delivery are still at the beginning. Here are a few highlights:

Nanoparticles:  Nanoparticles are currently the most studied branch of nanotechnology. Scientists at Rice University, Texas have developed small, uniform nanospheres of cerium oxide – a highly popular industrial antioxidant – which have the capability of treating cardiac arrest, traumatic brain injuries, and even Alzheimer’s.

At the time of a traumatic injury, for instance, blood contains increased levels of reactive oxygen species, which deprive cells of their oxygen and result in significant damage to their structures. By removing these free radicals from the bloodstream, cerium oxide nanoparticles can help cells survive, thus preventing further damage.

Magnetic Nanoparticles:  A team of researchers have developed magnetic nanoparticles that can be loaded with drugs or genes and directed towards deep targets in the body by using an external electromagnet.

As drug carriers, magnetic nanoparticles can allow clinicians to target hard-to-reach diseased sites inside our bodies, such as deep-tissue tumors, and avoid the need for systematically administered treatments or complex surgeries.

Self-healing and Injectable Nanomedicines:  A team of researchers have developed a variety of injectable nanomaterial that could accentuate the process of blood clotting and prevent blood loss in a near-fatal accident.

Even though the biomaterial is still being tested, the team believes that it could eventually be prefilled into syringes that users can inject on their own.

Safety
The term ‘‘nanotoxicology’’ first showed up in 2004. The details about possible risks have been described and considered from various angles. Although many individual researches have warned that nanomaterials can cause damage to the human body, the exact mechanisms of toxicity are unknown and conclusive data are yet to be established. Moreover, reports on nano-toxicity mostly focus on inorganic nanomaterials consisting of heavy metals. Investigation about the toxic effect of polymeric nanomaterials on living subjects is also urgently required.

Nanotechnology for Future Drug Delivery Systems
Predicting the future of nanotechnology in drug delivery systems is not simple because the technology is moving forward fast and dynamically changing, and we are in the middle of such changes. One could, however, find possible clues from the efforts to overcome the problems facing the research community today. One of the first things that can be predicted is the small design of drug delivery systems. Also multifunctional drug delivery systems have been reported, but only few of them were used successfully in small animal models. Recently, the layer-by-layer (LBL) coating technique was introduced to generate multifunctional polymer coating layers, and this LBL technique is expected to find many applications in developing various composites. While nanotechnology is expected to produce new nano/micro devices, it is also expected to revolutionize the way the current drug delivery systems are produced. For example, nano/micro particles are currently made by solvent evaporation/extraction or solvent exchange methods. These approaches have been successfully used in producing a variety of nano/micro particles containing pharmaceutically active ingredients, but the processing methods require significant improvements. Nanotechnology-based approaches, which is often called ‘‘nano/micro fabrication’’ or ‘‘nano/ micro manufacturing,’’ can provide powerful new ways for mass production of nano/micro particles with high drug loading efficiencies. As nanotechnology becomes mature, nano/micro devices are expected to become as practical as macro devices are today. Drug delivery, although it sounds simple, requires complicated adaptation of various fusion technologies to be clinically useful. For example, drug delivery systems with targeting ability require material science for making the right polymers, biology for finding the right ligands able to interact with targets, physics to monitor the location of delivery systems, and chemistry for releasing the active at the right time and place.