Current Pharmaceutical Biotechnology - Volume 6, Issue 1, 2005

Nanotechnology is a technology started as a collection of curiosities (sun screens, stain resistant pans and more). Special properties make nanoparticle so beneficial to medicine, why nanotechnology has entered biotechnological fields so rapidly. Nanostructured material is able to enter cells, cross the blood brain barrier or show a controlled release of drugs from matrix material in the gastrointestinal tract. But the question arises, what is nanobiotechnology? A clear definition does not exist, and it can be understood as a mixture of nanotechnology and biotechnology. Simply put, nanobiotechnology deals not with special areas and is understood as a matter of nanoscale level varying between 0.1 and 250 nm. Nanobiotechnology is maybe defined as technology concerned with materials and systems whose structures exhibited improved physical, chemical and biological properties in living organisms due to their nanoscale size. Special fields are electronics, telecommunications and life sciences including diagnostics, implantants, drug delivery, molecular biology, medicine, and biotechnology. Especially in nanomedicine research is advancing at several fronts. Creating nanoscaled drug carriers or even milling drug crystals in nanoparticles is one actual approach in nanomedicine as a new drug formulation for poorly soluble drugs. Recently the drugs rapamycine (Rapamune®) and aprepitant (Emend®) based on the NanoCrystal® technology have entered the market. The Second area that is highly influenced by nanotechnology in pharmaceutical biotechnology are diagnostics in clinics, biosensors in food industry and microarrays. The company NanoInk recently released the Nscriptor based on atomic force microscopy technology. An ultra fine probe can deposited liquids directly and in close proximity on nearly all surfaces. Such devices can be used to generate so called "point-of-care-diagnostics" to speed up clinical diagnostics in quality and quantity. Today we have a very enthusiastic view of nanobiotechnology, and we see a bright future with self replicating nanoscaled robots and artificial life mimicking natural processes as molecular machine. We must be aware, that there is no risk assessment for negative health and environment consequences. Only a few toxicological studies devoted to nanostructured material have been conducted. Properties of drugs are in some ways different at nanoscale, and because of the small size particles enter not only target cells but also healthy cells with unkown consequences. Today complex nanotechnologies are far from FDA or EMEA approval, and it can be expected that drug authorities will have critical view slowing down progress because of risk assessment. Some companies have recognised this problems and spinning their innovations not as drugs but as medical devices providing an easier approval. In this special issue Nanobiotechnology in pharmaceutical sciences will be highlighted from different experts. Starting with actual topics in fundamental research, drug applications in pharmacy and medicine are discussed to end up with an outlook of upcoming future techniques that have the potential to be moved into to treatment arena. In addition, some proposals for nanoparticles and nanoscale tools and their applications in medicine are reviewed and discussed. The issue presents lot examples, illustrating the progress in multidisciplinary research in nanoscaled biotechnology and nanomedicine. It is focused especially on drug aspects and the wide usage of diagnostics in various fields of science.

Nanotechnology, or systems/devices manufactured at the molecular level, is a multidisciplinary scientific field undergoing explosive development. A part of this field is the development of nanoscaled drug delivery devices. Nanoparticles have been developed as an important strategy to deliver conventional drugs, recombinant proteins, vaccines and more recently nucleotides. Nanoparticles and other colloidal drug delivery systems modify the kinetics, body distribution and drug release of an associated drug. Other effects are tissue or cell specific targeting of drugs and the reduction of unwanted side effects by a controlled release. Therefore nanoparticles in the pharmaceutical biotechnology sector improve the therapeutic index and provide solutions for future delivery problems for new classes of so called biotech drugs including recombinant proteins and oligonucleotides. This review discusses nanoparticular drug carrier systems with the exception of liposomes used today, and what the potential and limitations of nanoparticles in the field of pharmaceutical biotechnology are.

Anti-mRNA and particularly antisense oligonucleotides are molecules able to inhibit gene expression after intracellular penetration being potentially very interesting for the treatment of ocular diseases where growth factors are involved such as ocular scarring diseases or for the inhibition of viral multiplication. In most cases, the site of action of oligonucleotides has shown to be the posterior segment of the eye and these molecules are injected mainly by the intravitreal route. However, oligonucleotides are poorly stable in biological fluids, have a low intracellular penetration and are quickly eliminated form the vitreous. These issues request repeated administration of oligonucleotides which are able to induce severe damages to the retina. This is the reason why drug delivery systems were developed to improve the stability and intracellular penetration of oligonucleotides and, by sustained release, to increase their long term activity in the treatment of ocular diseases.

At the beginning of 21st century, fifty years after discovery of deoxyribonucleic acid (DNA) double helix structure, scientific world is faced with a great progress in many disciplines of biological research, especially in the field of molecular biology and operating on nucleid acid molecules. Many molecular biology techniques have been implemented successfully in biology, biotechnology, medical science, diagnostics, and many more. The introduction of polymerase chain reaction (PCR) resulted in improving old and designing new laboratory devices for PCR amplification and analysis of amplified DNA fragments. In parallel to these efforts, the nature of DNA molecules and their construction have attracted many researchers. In addition, some studies concerning mimicking living systems, as well as developing and constructing artificial nanodevices, such as biomolecular sensors and artificial cells, have been conducted. This review is focused on the potential of nanotechnology in health care and medicine, including the development of nanoparticles for diagnostic and screening purposes, the manufacture of unique drug delivery systems, antisense and gene therapy applications and the enablement of tissue engineering, including the future of nanorobot construction.

Nanotechnology concerns the science of very small particles and deals with both the fundamental aspects of understanding the properties of such nanoparticles and with developing technological applications of nanoparticles. Biomedical and biotechnological applications of nanoparticles have been of special recent research and development interest, with potential applications that include use of nanoparticles as drug (or DNA) delivery vehicles, and as components in medical diagnostic kits, biosensors and membranes for bioseparations. Spherical nanoparticles are typically used for such applications, but this only reflects the fact that spheres are easier to make than nanoparticles having other shapes. Micro and nanotubes - structures that resemble tiny drinking straws - are alternatives and may offer advantages over spherical nanoparticles for some applications. This article discusses different approaches for making micro and nanotubes and reviews the current status of efforts to develop biomedical and biotechnological applications of these tubular structures.

The drug delivery system described here is based on a virus like particle consisting of the recombinant expressed major capsid protein of Polyomavirus, VP1. Polyoma, a murine virus belonging to the Papovaviridae, forms a non-enveloped icosahedral capsid. These capsids are organized as a double shell composed of three different proteins: VP1,VP2 and VP3. The outer shell of the vision is composed of 360 VP1 molecules arranged as 72 pentamers. These capsids have a diameter of about 50 nm. The VP1 protein acts as a major ligand for certain membrane receptors during virus infection. Furthermore, the N-terminus of the VP1 protein contains a DNA-binding domain and a nuclear localization sequence. The recombinant production of the VP1 protein offers a save way to obtain a highly purified, non-pathogenic pharmaceutical excipient. Combining these aspects, VP1 proteins provide a targeting as well as a drug binding site when used as a save drug carrier for gene therapy. Current applications are also including oligonucleotides as well as small molecules as well as vaccines.

The advances in the microelectronics fabrication allow the strong appearance of micro-electro-mechanical systems known as MEMS. MEMS enable the fabrication of smaller devices that are manufactured using standard microfabrication techniques similar to the ones that are used to create computer silicon chips. Several MEMS devices including micro-reservoirs, micro-pumps, cantilevers, rotors, channels, valves, sensors, and other structures have been designed, fabricated and tested from using materials that have been demonstrated to be biocompatible. This paper reviews the status of Micro-electronic and MEMS systems that can be used for adaptive drug administration. It presents different components and describes a possible implementation. Finally it presents a prototype that is termed ipill which stands intelligent pill.

This article is a selective extension of a review on recombinant human erythropoietin (rHu-EPO) as an antianaemic drug, published in this journal in 2000. It summarises the recent advances in understanding the molecular mechanisms by which the hypoxia-inducible transcription factor 1 (HIF-1) regulates O2-dependent genes, including the EPO gene in brain. With respect to brain integrity, EPO exerts positive effects in two different ways. First, rHu-EPO raises the blood haemoglobin concentration and, hence, the O2 capacity of the blood in anaemic patients. The restored O2 supply ameliorates attention difficulties and psychomotor slowing, improves memory capacities and normalises neuroendocrine functions. Second, EPO can act as a neurotrophic and neuroprotective factor directly in brain. EPO and its receptor are expressed in the cerebral cortex, cerebellum, hippocampus, pituitary gland and spinal cord. In vitro EPO protects against glutamate-induced cell death in a dose-dependent way. In animal models it reduces volumes of brain ischaemia, protects the cortex from hypoxic damage and leads to survival of neurons and synapses. One can expect that in the near future rHu-EPO will be used therapeutically in cerebral ischaemia, brain trauma, inflammatory diseases, and neural degenerative disorders. A first clinical trial has shown the neuroprotective effectiveness of the drug in cerebral ischaemia.

Recent advances in biotechnology have promoted biomolecular targeting of drugs, peptides and genes in the treatment and management of major diseases and infections. Therapeutic development of drugs and delivery systems may have various objectives: Systemic drugs require optimal delivery and uptake at target sites; peptide drugs require alternative routes of administration, such as nasal or intestinal absorption; gene medicines need to be delivered efficiently, safely and selectively to diseased areas. The propensity of ligand-modified liposomes to carry drugs and genes to desirable sites has been extensively examined and current reports show considerable progress in this field. Sterylglucoside (SG) is a novel absorption-enhancer of peptide drugs across nasal and intestinal mucosae. Physico-chemical properties and biodistribution of liposomes incorporating SG were studied and compared against the profiles of aglycon and sitosterol derivatives of SG. It was shown that SG particles aided colon drug delivery and increased bioavailability of peptide drugs after nasal and intestinal administration. In addition, they were able to enhance anticancer effects in liver cancer chemotherapy. Biological fate and interaction of SG with hepatocytes support the novel proposition of liver-targeting SGliposomes.