Advanced Drug Delivery Reviews 55 (2003) 311–313www.elsevier.com/ locate/addr

Preface

B iomedical 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 bedistinct technological advantages of reduced dimen- distinguished from the nanoscience enabling suchsional scales to sizes approaching individual mole- technology. Additionally, enthusiasm for thecules 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 ofbut also functional enhancement gains over conven- Nanotechnology (www.nano.org.uk) maintains thattional technology in the context of commercializa- little private investment is flowing to nanotechnologytion. Molecular self-assembly, circuits, molecular to date because this sector still shows immaturity.manipulation, self-replication, switches, motors, Few tangible commercial applications with readilymemory storage, surface patterns, medicines, and perceived performance advantages are yet to be seenmaterials are commonly cited examples. Structure- among the various activities. Nanotechnology is stillproperty and spatial relationships become critical at very young. By contrast, nanoscience is much moresize scales where fewer molecules are relied upon to vibrant and mature, with the ultimate intent ofelicit desired function in organized ensembles. The realizing applications downline: both the U.S. andidea that ‘‘smaller can be better’’ drives the current Japan have national nanotech research initiativesnanotechnology 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 fromscope, or exhibits quantum confined optical or private sectors in nano-related venture activities. Allelectrical 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 bynanotechnology. Simply achieving sub-micron size 2012, according to the U.S. National Sciencestructures and molecular organization is frequently Foundation.an epic achievement in itself for some device With the hype and blur between science andprotoypes. Yet, further proof that such down-sizing applications, nanotechnology seems to be one ofactually improves device function or imparts new those words at risk of losing any specific meaning orbeneficial 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, conventionalfilled with gee-whiz ‘‘gadgetizing’’ based on shrink- photolithography with feature sizes historically in theing 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, whileWithout the latter applications, simple fabrication is sub-micron structural benchmarks, have no provenonly preliminary – a requisite for eventual technolo- function. Other mesoscale constructs, includinggy, but not necessarily technology itself unless new many reported vesicles, larger molecular aggregates

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312 Preface 55 (2003) 311–313

and particles, fibers and tubes, transistors, optical and sophisticated, and may indeed prove morewaveguides and switches, microfluidics channels and therapeutically efficacious. Like all sciences, phar-valves, and microarrays, are or will be reduced maceutical nanoscience must also necessarily evolvedimensionally to sub-micron sizes. Whether this into appropriate, proven nanotechnology to provenano-sizing produces new performance impacts lead- practical utility. Reductions in device size or scale ofing to technological improvements remains to be the approach must be coupled with evidence forseen in many cases. But, such proof iscritical for the impact, benefit, and enhanced performance.nanotechnology craze to maintain credibility in Unlike other technology sectors, nano-scale drugscientific 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 provenbased 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 beenmacogenomic 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 likeobjectives, 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 tomay not be in functional context, we might better target the organismal organization and function inintroduce the intent of this specialADDR 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 evolvingtherapeutic value is readily ascertained. Hence, requirement for clinical therapeutics and diseasenanotechnology impacts from drug delivery and diagnosis at the molecular level by matching thepharmaceutics approaches should be distinctive. appropriate innovative efforts to advance molecularFortunately, 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 processesmolecular 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, nanotechnologyceptor recognition, organelle barrier construction, and nanoscience in drug delivery and therapeuticscell 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 theirter scale – the size scale of an amino acid building approach.block, a nucleotide, a lipid, secondary interactions ThisADDR issue includes contributions focusingproducing structure and function in proteins and on selected, recent nanoscience and technologyDNA, 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 developmentsbrane barriers and their channels – is an appropriate for microanalysis systems (mTAS) relevant to drugdimension 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, andnew approaches at this same scale. Rather than a coupled cellular signaling. Two further contributionssystemic therapeutic approach, molecular-level stra- focus on recent developments in two different typestegies to construct, assemble, manipulate, target, of molecular nanoparticle drug delivery. One contri-deliver, trigger, detect, recognize, store, deposit, bution reviews progress in soluble polymer targetingdiagnose, and treat disease are certainly more elegant of cells with complex conjugated drug delivery

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

David W. Grainger(Theme Editor)

Department of ChemistryColorado State University

Ft. Collins, CO 80523-1872USA

E-mail: grainger@lamar.colostate.edu

Teruo Okano(Theme Editor)

Institute of Advanced Biomedical Engineeringand Science

Tokyo Women’ s Medical UniversityShinjuku-ku, Tokyo 162-8666

JapanE-mail: tokano@lab.twmu.ac.jp