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					                                     Advanced Drug Delivery Reviews 55 (2003) 311–313
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                          Biomedical micro- and nano-technology

   Technology is generally regarded as the utilization                  methods applied to achieve these ends are them-
or application of science to benefit society. The                        selves enabling.
burgeoning field of nanotechnology seeks to exploit                          So, nanotechnology and its potential value must be
distinct technological advantages of reduced dimen-                     distinguished from the nanoscience enabling such
sional scales to sizes approaching individual mole-                     technology. Additionally, enthusiasm for the
cules and their organized aggregates. Implicit in this                  nanotechnology hype and hyperbole must be tem-
definition is not only realization of devices, con-                      pered against the current infancy of such technology.
structs, methods, and techniques at this size scale,                    A recent white paper originating from the Institute of
but also functional enhancement gains over conven-                      Nanotechnology ( maintains that
tional technology in the context of commercializa-                      little private investment is flowing to nanotechnology
tion. Molecular self-assembly, circuits, molecular                      to date because this sector still shows immaturity.
manipulation, self-replication, switches, motors,                       Few tangible commercial applications with readily
memory storage, surface patterns, medicines, and                        perceived performance advantages are yet to be seen
materials are commonly cited examples. Structure-                       among the various activities. Nanotechnology is still
property and spatial relationships become critical at                   very young. By contrast, nanoscience is much more
size scales where fewer molecules are relied upon to                    vibrant and mature, with the ultimate intent of
elicit desired function in organized ensembles. The                     realizing applications downline: both the U.S. and
idea that ‘‘smaller can be better’’ drives the current                  Japan have national nanotech research initiatives
nanotechnology frenzy. However, just because a                          worth over a half billion dollars each this year,
device can only be visualized with a probe micro-                       matching nearly equal funding internationally from
scope, or exhibits quantum confined optical or                           private sectors in nano-related venture activities. All
electrical properties, or can be measured in nano-                      this seeks to address developing international mar-
dimensional units doesn’t necessarily mean it’s                         kets projected to be worth nearly a trillion dollars by
nanotechnology. Simply achieving sub-micron size                        2012, according to the U.S. National Science
structures and molecular organization is frequently                     Foundation.
an epic achievement in itself for some device                               With the hype and blur between science and
protoypes. Yet, further proof that such down-sizing                     applications, nanotechnology seems to be one of
actually improves device function or imparts new                        those words at risk of losing any specific meaning or
beneficial technological properties conferring tech-                     significance due to the current trend of over-use,
nology is often elusive or unconvincing. Journals are                   particularly inappropriate use. Indeed, conventional
filled with gee-whiz ‘‘gadgetizing’’ based on shrink-                    photolithography with feature sizes historically in the
ing size scales and molecular manipulations, but not                    micron range is not nanotechnology, nor are re-
necessarily proving practical or commercial utility.                    sulting milled or fabricated components that, while
Without the latter applications, simple fabrication is                  sub-micron structural benchmarks, have no proven
only preliminary – a requisite for eventual technolo-                   function. Other mesoscale constructs, including
gy, but not necessarily technology itself unless new                    many reported vesicles, larger molecular aggregates

0169-409X / 02 / $ – see front matter  2002 Elsevier Science B.V. All rights reserved.
312                                           Preface 55 (2003) 311–313

and particles, fibers and tubes, transistors, optical          and sophisticated, and may indeed prove more
waveguides and switches, microfluidics channels and            therapeutically efficacious. Like all sciences, phar-
valves, and microarrays, are or will be reduced               maceutical nanoscience must also necessarily evolve
dimensionally to sub-micron sizes. Whether this               into appropriate, proven nanotechnology to prove
nano-sizing produces new performance impacts lead-            practical utility. Reductions in device size or scale of
ing to technological improvements remains to be               the approach must be coupled with evidence for
seen in many cases. But, such proof is critical for the       impact, benefit, and enhanced performance.
nanotechnology craze to maintain credibility in                  Unlike other technology sectors, nano-scale drug
scientific circles and in the market place. The                delivery approaches already have a relatively estab-
Institute white paper indicates that nano-particle            lished, diversified research record, with proven
based paints, pigments and coatings represent the             promise of benefit. Many molecular therapeutic,
most likely closest market, with custom phar-                 imaging, triggering, and releasing agents have been
macogenomic drugs, diagnostics, and cosmetics lead-           fully developed and reported as molecularly de-
ing markets only after a decade or so. Biosciences            signed, organized ensembles, and functional devices.
clearly embrace promising further nanotechnology              Rather than slap a new name on old concepts like
objectives, with imaging agents, delivery devices,            other areas of science appear to have done, pharma-
biomedical and analytical tools, sensors, and inte-           ceutical nanotechnology has a precedent: a well-
grated separation nanokits likely prospective targets.        established molecular focus and basis for such design
   Having proposed what nanotechnology may or                 by integrating therapeutic tool designs directly to
may not be in functional context, we might better             target the organismal organization and function in
introduce the intent of this special ADDR issue on            human biology and medicine. Departments of Mo-
nanotechnology in drug delivery. Drug delivery is,            lecular Medicine now seen emerging in many Ameri-
by practical definition, functionally based: clinical          can medical schools seem to respond to the evolving
therapeutic value is readily ascertained. Hence,              requirement for clinical therapeutics and disease
nanotechnology impacts from drug delivery and                 diagnosis at the molecular level by matching the
pharmaceutics approaches should be distinctive.               appropriate innovative efforts to advance molecular
Fortunately, biological function of the human organ-          approaches to disease management. Nano-scale ther-
ism clearly is design-based on a hierarchy of size            apeutic approaches are continually undergoing verifi-
scales. At the most fundamental level, function and           cation in an applied context through time-consuming,
structure necessary for life result from specific              costly clinical trials and clinical approval processes
molecular shapes – antibody and enzyme binding                required for validation, efficacy and market entrance.
sites, transcription factor-DNA interactions, cell re-        Thus, unlike other areas of science, nanotechnology
ceptor recognition, organelle barrier construction,           and nanoscience in drug delivery and therapeutics
cell cytoskeletal assembly, cell transport and com-           are, by necessity, often integrated and directly fo-
munication, and cell–cell recognition. The nanome-            cused on function and efficacy as validation for their
ter scale – the size scale of an amino acid building          approach.
block, a nucleotide, a lipid, secondary interactions             This ADDR issue includes contributions focusing
producing structure and function in proteins and              on selected, recent nanoscience and technology
DNA, electron transfer, proton transfer and ion               strategies in drug delivery and screening. Specifical-
transport distances, and the thickness of cell mem-           ly, three articles describe lab-on-chip developments
brane barriers and their channels – is an appropriate         for microanalysis systems (mTAS) relevant to drug
dimension to think about issues of advanced drug              screening in vitro, bioreactions and synthesis, mix-
delivery, and also to develop innovative, creative            ing, bioanalysis, pharmacology and toxicology, and
new approaches at this same scale. Rather than a              coupled cellular signaling. Two further contributions
systemic therapeutic approach, molecular-level stra-          focus on recent developments in two different types
tegies to construct, assemble, manipulate, target,            of molecular nanoparticle drug delivery. One contri-
deliver, trigger, detect, recognize, store, deposit,          bution reviews progress in soluble polymer targeting
diagnose, and treat disease are certainly more elegant        of cells with complex conjugated drug delivery
                                              Preface 55 (2003) 311–313   313

systems, and a further review describes micro-fabri-
cated solid-state constructs versatile for drug delivery
systems. Collectively, these contributions for this
issue on ‘‘Biomedical Micro- and Nano-technology’’
adequately and comprehensively round out important
scientific and technical perspectives for topical areas
of focus in this area relevant to pharmaceutics and
drug delivery.

                                   David W. Grainger
                                      (Theme Editor)

                           Department of Chemistry
                          Colorado State University
                        Ft. Collins, CO 80523 -1872

                                         Teruo Okano
                                       (Theme Editor)

      Institute of Advanced Biomedical Engineering
                                        and Science
                 Tokyo Women’ s Medical University
                       Shinjuku-ku, Tokyo 162 -8666

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