Nanotechnology and Drug Delivery, Volume One: Nanoplatforms in Drug Delivery

378 Pages·2014·8.244 MB·English

by  José L. Arias

Nanotechnology and
Drug Delivery
Volume 1: Nanoplatforms in Drug Delivery

Nanotechnology and
Drug Delivery
Volume 1: Nanoplatforms in Drug Delivery
Editor
Professor Dr. José L. Arias
Department of Pharmacy and Pharmaceutical Technology
Faculty of Pharmacy
University of Granada
Campus Universitario de Cartuja s/n
18071 Granada, Spain
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A SCIENCE PUBLISHERS BOOK
GL--Prelims with new title page.indd ii 4/25/2012 9:52:40 AM
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Preface to The Book Series
Pharmacotherapy is frequently associated with ineffi cacy and toxicity
problems limiting disease treatment and prognosis and the quality of
life of patients. Such incidences have been described even during the
clinical use of new drug molecules, dosage forms and more sophisticated
treatment schedules. To beat the challenge, recent advances in drug therapy
have involved the introduction of nanotechnology in the development
of medicines. In fact, drug-loaded nanoplatforms (the so-called
nanomedicines) are expected to become the definitive step toward a
successful pharmacotherapy. These nanocarriers are wisely engineered
to maximize drug accumulation into non-healthy tissues and cells, thus
optimizing the pharmacokinetics and pharmacodynamics of active
molecules, while minimizing their systemic side effects. In addition, new
synthesis methodologies in nanomedicine formulation, the theranosis
conceptualization, have made possible to combine disease diagnosis and
therapy, thus opening the door to “personalized” medicines.
In line with all these revolutionary progresses in the drug delivery
fi eld, “Nanotechnology and Drug Delivery” is a series of two volumes
analyzing the fundaments and more advanced aspects in the development of
nanomedicines. The selected book chapter contributions have been written
by well-known experts in the fi eld, and comprise insights into the most
promising moves toward superior drug-loaded nanoplatforms. Original
concepts derived from advanced materials science, physical chemistry and
medicinal chemistry with critical applicability into the clinic are emphasized
in the book series.
The fi rst volume “Nanoplatforms in Drug Delivery” is focused on the
physicochemical engineering of nanomedicines, their pharmacokinetics,
biocompatibility and biodegradability aspects, representative nanoplatforms
(based on lipids, polymers, cyclodextrins, metals, carbon, silica, iron oxides,
etc.) for an effi cient drug delivery, and advanced nano-engineering strategies
for passive, ligand-mediated and/or stimuli-sensitive drug targeting. As
an ideal complement to this book, the second volume “Nano-Engineering
Strategies and Nanomedicines against Severe Diseases” further discusses
the possibilities of nanotechnology, in the context of nanomedicine, for
vi Nanotechnology and Drug Delivery
oral, dental, topical and transdermal, pulmonary and nasal, ocular and otic,
vaginal and brain drug delivery and targeting. Furthermore, an updated
point of view is given to nanomedicines against severe diseases, i.e., cancer,
cardiovascular diseases, neurodegenerative disorders, infectious diseases,
chronic infl ammatory diseases and metabolic diseases. Gene delivery and
the recent concept of nanotheranosis are also analyzed in the book.
In my opinion, the book series will give a complete overview on the
current state of the art, including more revolutionary conceptualizations,
and future perspectives in nanotechnology and drug delivery. It will also
be a vast source of knowledge not only to non-expert but also to senior
researchers in the fi eld of advanced drug delivery to severe diseases. Last
but not least, I would like to thank all the contributors to the book series
for the excellent work accomplished. It has been a privilege to work with
them.
Professor Dr. José L. Arias
Preface to Volume 1
The development of platforms for drug delivery purposes have been
classically based on the engineering of micro- and nano-particulate systems
that can optimize the specifi city of any given active agent for the disease site.
However, conventional drug carriers were found unable to perfectly meet
the challenge, mainly given their inadequate pharmacokinetic properties
(rapid plasma clearance and elimination by the reticuloendothelial
system) and poor drug vehiculization capabilities (low loading values
and rapid release). As a consequence, there was a huge demand for new
ideas revolutionizing the status quo in the drug delivery arena. In this line,
recently published research articles have described the benefi ts coming from
engineering nanoplatforms with excellent drug vehiculization properties,
and capable of perfectly controlling the biological fate of drug molecules:
maximization of drug levels into non-healthy tissues and/or cells (drug
effi cacy), while drug biodistribution into non-targeted sites is kept to a
very minimum (drug safety).
In line with this reconceptualization of drug delivery, the fi rst volume
“Nanoplatforms in Drug Delivery” of the book series “Nanotechnology
and Drug Delivery” is devoted to the analysis and discussion of the most
representative physicochemical engineering approaches to the formulation
of nanocarriers with the best drug vehiculization characteristics and
controllable biological fate. In this respect, an important factor to be
considered is the material to be used in nanoplatform development, i.e.,
polymers, cyclodextrins, lipids, carbon, silica, metals, iron oxides, etc. In
fact, only an intelligent design and chemical engineering of the particulate
structure will assure a satisfactory drug loading and release, an effi cient
in vivo behavior, biocompatibility and biodegradability and adequate
pharmacokinetic properties. Even more, engineering strategies for passive,
ligand-mediated and/or stimuli-sensitive drug targeting clearly depend on
the materials used in the formulation of the nanomedicine.
The selected book chapters included in this book comprise insights
into the most promising moves toward conventional and more advanced
conceptualizations in nanomedicine formulation coming from physical
chemistry, materials science, and medicinal chemistry. Chapter 1 (Key
Aspects in Nanotechnology and Drug Delivery) could be considered as
viii Nanotechnology and Drug Delivery
an interesting introduction to the design and synthesis of drug-loaded
nanoplatforms which updates the current state of the art and future
perspectives in the fi eld. Essential elements to be included in the preparation
of competent drug delivery systems are analyzed, including basic
nanotoxicity concepts, and particular attention is given to the description
of formulation strategies facilitating the control over nanoparticle
biodistribution, and the development of theranostic nanotools.
At this point in the book, the reader will be able to gain access to chapters
devoted to the most representative materials selected for the synthesis
of effi cient drug-loaded nanoplatforms. Concretely, Chapters 2 (Drug
Delivery and Release from Polymeric Nanomaterials) and 3 (Nano-Sized
Polymeric Drug Carrier Systems) by Prof. Vasile and co-workers discuss
the fundaments and recent advances in the preparation of polymer-based
drug delivery systems. The authors also describe the most important aspects
related to their rational design and (bio)evaluation, i.e., stability, drug
vehiculization capacity (loading and release properties), correlation between
design and drug release properties, interconnection between the route of
administration and mechanism of drug release, kinetics/pharmacokinetics
and biodistribution.
The contribution by the research group of Prof. Lam (Chapter 4:
Reversible Cross-Linked Polymeric Nanoplatform in Drug Delivery) discuss
the promising development of reversibly cross-linked polymeric micelles
for targeted drug delivery. These nanoplatforms are characterized by a
superior structural stability, and the capability to respond to endogenous
and/or exogenous stimuli that can modulate drug release. The chapter is
further focused on the strategies used for the design, preparation and cross-
linking, stimuli-responsive capability and triggered drug release. In vitro
and in vivo evidence demonstrating the effectiveness of reversibly cross-
linked micelles is also presented and, of course, biomedical applications
and future perspectives in their development are explored.
The potential use of cyclodextrins in drug delivery is carefully
analyzed by Prof. Bilensoy and co-worker (Chapter 5: Cyclodextrins in
Drug Delivery). This chapter provides an interesting overview on the most
important characteristics (i.e., stability, drug solubility and dissolution,
bioavailability and safety), and use of cyclodextrins and their derivatives as
excipients in drug formulation and in the design of advanced drug delivery
systems, e.g., liposomes, microspheres, microcapsules and nanoparticles.
Recent developments and future perspectives related to the technology
of biodegradable nano-sized drug carriers made of tyrosine-derived
amphiphilic block copolymers are examined in Chapter 6 [Drug Delivery
Systems Based on Tyrosine-derived Nanospheres (TyroSpheres™)] by Prof.
Michniak-Kohn and co-workers. TyroSpheres™ are vehicles for lipophilic
drugs made of tyrosine dipeptide derivatives, naturally occurring diacid
Preface to Volume 1 ix
and poly(ethylene glycol), while the hydrophobic segments of polymers
are based on naturally occurring metabolites. It is justifi ed in the chapter
how chemical composition determines the physicochemical properties
and core-shell structure of these drug delivery systems and, thus, the drug
vehiculization properties and in vivo fate. In addition, the potential use of
TyroSpheres™ for the topic and intravenous delivery of drug molecules in
the treatment of skin diseases and breast cancer is discussed.
Recent achievements in the formulation of carbon nanotubes for drug
delivery purposes are very carefully described by Prof. Rosen and co-
worker in Chapter 7 (Carbon Nanotubes for Drug Delivery Applications).
Their large surface area, high aspect ratio and extraordinary electrical and
mechanical characteristics have called the attention of scientists. Synthesis
methodologies, toxicological aspects and applications of carbon nanotubes,
ranging from cancer therapy to gene therapy, are also commented on in
the chapter.
Chapter 8 (Metallic Nanoparticulate Drug Delivery Systems) by the
research group of Prof. Pokharkar analyzes the introduction and possibilities
of metal- and metal oxide-based nanoparticulate tools in targeted drug
delivery. More relevant synthesis procedures, biological and design aspects,
and surface engineering approaches in nanoparticulate development
are also the objective of this contribution. As well, the most signifi cant
properties, characterization methodologies, regulatory perspectives and
biomedical applications of metallic nanomaterials are emphasized in the
chapter.
Prof. Trewyn and co-worker focus on recent efforts in the development
of porous silica-based drug delivery systems, as well as investigations on
their in vitro and in vivo applications (Chapter 9: Porous Silica Nanoparticles
for Drug Delivery and Controlled Release). The contribution reviews the
more interesting approaches to the synthesis and characterization of versatile
porous silica nanoparticles, and current progress in their functionalization
with specifi c cell and antigen targeting moieties, organic components and
inorganic nanoparticles. It is also highlighted that a triggered drug release
from these nanoplatforms is possible by physical, chemical or biological
external or internal stimuli. Finally, this chapter also includes an analysis
of the investigations on the biocompatibility and on the internalization
effi ciency of porous silica nanoparticles by cells.
The contributions written by Prof. Sahoo and co-worker (Chapter 10:
Iron Oxides in Drug Delivery), and Prof. Misra (Chapter 11: Nanoengineered
Magnetic Field-Induced Targeted Drug Delivery System with Stimuli
Responsive Release) extend the interest of the book to the use of iron
oxides in drug (and gene) delivery and hyperthermia. In fact, Chapter 10 is
devoted to the analysis of the more representative preparation procedures
to obtain iron oxide nanoparticles. Interestingly, the improvement of drug