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                                               Advanced Drug Delivery Reviews 60 (2008) 861 – 862

                   Clinical developments in drug delivery nanotechnology ☆

    Nanotechnology is attracting increasing attention in the                    candidate for nanosuspension formulation, how these formula-
biomedical community, owing to unique prospects for targeted                    tions are characterized, and the impact nanosuspension
delivery in imaging, gene therapy, and drug delivery. Going                     characteristics may have on biological effect and safety.
small has many theoretical benefits from a targeted delivery                        Nanotechnology seeks to increase the therapeutic index of
perspective, and multidisciplinary efforts are driving remark-                  drugs both by improving their administration and by increasing
able advances in the development of nanoscale delivery                          the exposure of diseased tissues to therapeutics. Polymeric
systems, so-called ‘nanocarriers’ or ‘nanomachines,’ which                      micelles are self-assembled nanoparticles that can solubilize
have started to affect clinical practice. The goal of this current              poorly soluble drugs in their hydrophobic core. The precise size
issue of Advanced Drug Delivery Reviews is to summarize                         control possible with these nanoparticles makes possible
recent developments in drug delivery, focusing on nanotechnol-                  passive targeting to tumors via the enhanced permeability and
ogy that has entered the clinical arena or is making dramatic                   retention (EPR) effect. Several new formulations of chemother-
impacts on new drug development. In each case, nanocarriers                     apeutic drugs, i.e. paclitaxel, cisplatin, and camptothecin, are in
have illustrated clear cut improvements in the delivery of                      clinical development. Dr. Matsumura of the National Cancer
proven drugs or compounds in the development pipeline, which                    Center Hospital in Tokyo has authored several clinical trials of
suffer from impediments, precluding or hindering drug devel-                    micellar nanotechnologies in Japan. Dr. Matsumura discusses
opment: poor water solubility, low bioavailability, or toxicity.                the preclinical and clinical development of these nanocarriers
Thus, nanotechnology has the potential to be a major                            and outcomes of early human trials.
component of the drug development process, which has relied                         Polymer conjugates of anticancer drugs may further improve the
on conventional formulation strategies that are often inade-                    safety and action of these agents over conventional formulations,
quate. A partnership of drug and nanocarrier, as illustrated in                 and several polymer–drug conjugate nanoparticles have pro-
this issue, represents a changing paradigm in drug development,                 gressed to Phase I/II/III trials. Drs. Li and Wallace of M.D.
raising broad implications for many clinical efforts in many                    Anderson Cancer Center review the advantages and limitations of
disease states, most notably in cancer.                                         this technology and the results of early human trials.
    Abraxane® was the first nanoparticle drug formulation to                        Vaccination has had a dramatic impact on worldwide human
receive FDA approval in 2005. Dr. Michael Hawkins, who                          health, but while we have successfully eradicated smallpox and
served as Chief Medical Office of Abraxis BioScience during                     nearly so polio, there is a critical need for new delivery systems
the development of Abraxane®, has provided an overview of                       to improve the stability, safety, and efficiency of new vaccines,
nanometer-albumin-bound (nab) drug development for pacli-                       especially when faced with the challenge of tackling HIV or
taxel and the benefits nab technology has over conventional                     even cancer. Several products utilizing aspects of nanotechnol-
(e.g. Cremophor EL®) formulations. As Dr. Hawkins points                        ogy in their formulation are already in the clinic, and these
out, the clinical success of Abraxane® has directly impacted                    technologies are being applied to future vaccine development.
future drug development. Albumin-bound formulations of other                    Drs. Peek, Berkland, and Middaugh review the application of
poorly soluble anti-cancer drugs are in clinical trials, demon-                 nanotechnology to vaccine adjuvants and delivery systems.
strating the immediate impact this success story has had on the                     Nanotechnology has clearly impacted the development of
acceptance of nanotechnology in the clinic.                                     new therapeutics, especially in the case of intravenous drug
    Insoluble drug formulation is one of the chief areas of drug                delivery, with multiple products either in the clinic or
delivery where nanotechnology promises to improve safety and                    development. Drug delivery to the lung has classically relied
efficacy. However, major hurdles can exist in the design and                    on micron-sized particles in order to achieve the most favorable
manufacture of these formulations, such as stability and                        disposition after inhalation, but as Dr. Löbenberg and co-
processing. Dr. Wong and coworkers at Baxter Healthcare                         workers discuss, nanoengineered materials may be utilized to
discuss the consideration of whether a new chemical entity is a                 improve drug delivery to the lungs. However, safety will be a
                                                                                chief concern as our final contributor discusses.
    This preface is part of the Advanced Drug Delivery Reviews theme issue on       Moving from micro to nano may improve the safety and
“Clinical Developments in Drug Delivery Nanotechnology”.                        efficacy of therapeutics, but the opposite could also be true. The
0169-409X/$ - see front matter © 2008 Elsevier B.V. All rights reserved.
862                                                      Preface 60 (2008) 861–862

incredibly small dimensions of these new materials can have                                                     M. Laird Forrest
profound, unexpected effects on their interaction with living                                                    (Theme Editor)
cells. Hence, there is on-going debate in scientific, industrial,
and regulatory communities regarding the safety of nanoparti-                                         Pharmaceutical Chemistry
cles. As Dr. Davies and co-workers discuss, we cannot assume                                           The University of Kansas
nanomaterials will have the same properties as their parent bulk                            2095 Constant Avenue, Lawrence, KS
materials, and there are unique toxicological consequences of                                                              USA
exposure to nanoparticles.                                                                                Corresponding author.
   Despite the surge of nanotechnology research in the past                                    E-mail address: mforrest@ku.edu
decades, few products have made it to market. New technologies
may excel in early preclinical trials but then stall amid the
realities of production and regulatory difficulties inherent to any                                               Glen S. Kwon
new, complex technology. In this issue of Advanced Drug                                                          (Theme Editor)
Delivery Reviews, properties of nanocarriers have been sum-
marized for a drug delivery point of view, highlighting strengths                                       Pharmaceutical Sciences
and weaknesses, and the outlook for clinical practice has been                                              School of Pharmacy
provided. We have invited the authors to give their insight into                                         University of Wisconsin
what properties of the featured nanotechnologies allowed them                                 777 Highland Avenue, Madison, WI
to succeed. Also, what stumbling blocks appeared along the                                                                  USA
way?                                                                                 E-mail address: gskwon@pharmacy.wisc.edu

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