| Current
Pharmaceutical Biotechnology
ISSN: 1389-2010
Current Pharmaceutical Biotechnology
Volume 6, Number 1, February 2005
Contents
Nanobiotechnology
Guest Editor: Oliver Kayser
Editorial
Oliver Kayser
[Editorial
In PDF]
The Impact of Nanobiotechnology on the Development
of New Drug Delivery Systems Pp.3-5
O. Kayser, A. Lemke and N. Hernandez-Trejo
[Abstract] [Full
text article]
Intraocular Delivery of Oligonucleotides Pp.7-15
A.L. Gomes Dos Santos, A. Bochot and E. Fattal
[Abstract] [Full
text article]
Nanotechnology on Duty in Medical Applications
Pp.17-33
T. Kubik, K. Bogunia-Kubik and M. Sugisaka
[Abstract] [Full
text article]
Smart Nanotubes for Biotechnology Pp.35-47
Punit Kohli and Charles R. Martin
[Abstract]
[Full text article]
Recombinant Virus Like Particles as Drug Delivery
System Pp.49-55
Christiane Georgens, Jorg Weyermann and Andreas Zimmer
[Abstract]
[Full text article]
An Integrated Platform for Bio-Analysis
and Drug Delivery Pp.57-64
S. Amer and W. Badawy
[Abstract]
[Full text article]
General Articles
Effects of Erythropoietin on Brain Function Pp.65-79
W. Jelkmann
[Abstract]
[Full text article]
Application of Sterylglucoside-Containing
Particles for Drug Delivery Pp.81-93
Yoshie Maitani, Koji Nakamura and Kumi Kawano
[Abstract]
[Full text article]
Abstracts
[Back to top]
Editorial
Oliver Kayser
[Editorial
In PDF]
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.
Oliver Kayser
Groningen 2004
[Back to top]
The Impact of Nanobiotechnology on the Development of New
Drug Delivery Systems
O. Kayser, A. Lemke and N. Hernandez-Trejo
[Full text
article]
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.
[Back to top]
Intraocular Delivery of Oligonucleotides
A.L. Gomes Dos Santos, A. Bochot and E. Fattal
[Full text
article]
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.
[Back to top]
Nanotechnology on Duty in Medical Applications
T. Kubik, K. Bogunia-Kubik and M. Sugisaka
[Full text
article]
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.
[Back to top]
Smart Nanotubes for Biotechnology
Punit Kohli and Charles R. Martin
[Full text
article]
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.
[Back to top]
Recombinant Virus Like Particles as Drug Delivery
System
Christiane Georgens, Jorg Weyermann and Andreas
Zimmer
[Full text
article]
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.
[Back to top]
An Integrated Platform for Bio-Analysis and Drug Delivery
S. Amer and W. Badawy
[Full text
article]
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.
[Back to top]
Effects of Erythropoietin on Brain Function
W. Jelkmann
[Full text
article]
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 normalizes 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.
[Back to top]
Application of Sterylglucoside-Containing Particles for Drug
Delivery
Yoshie Maitani, Koji Nakamura and Kumi Kawano
[Full text
article]
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
SG-liposomes.
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