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Nanotechnology and Drug Delivery Volume 2: Nano-Engineering Strategies and Nanomedicines against Severe Diseases Nanotechnology and Drug Delivery Volume 2: Nano-Engineering Strategies and Nanomedicines against Severe Diseases Editor Professor Dr. José L. Arias Department of Pharmacy and Pharmaceutical Technology Faculty of Pharmacy University of Granada Granada Spain p, A SCIENCE PUBLISHERS BOOK GL--Prelims with new title page.indd ii 4/25/2012 9:52:40 AM GL--Prelims with new title page.indd ii 4/25/2012 9:52:40 AM CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2016 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Version Date: 20160210 International Standard Book Number-13: 978-1-4822-6273-5 (eBook - PDF) This book contains information obtained from authentic and highly regarded sources. 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For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www. copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750- 8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identi- fication and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com 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 incidents 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 defi nitive 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 this revolutionary progress in the drug delivery fi eld, “Nanotechnology and Drug Delivery” is a series of two volumes analyzing the fundamentals 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 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, vi Nanotechnology and Drug Delivery: Volume 2 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 for non-experts but also for 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 2 Nanomedicine development is revolutionizing the disease arena. Numerous preclinical and clinical investigations are demonstrating the possibilities coming from the vehiculization of therapeutic molecules into nanoparticulate platforms, not only in terms of improvement of the therapeutic effect but also by minimizing the associated toxicity. As a result, nanomedicines are being introduced into the clinic. Disease diagnosis has also taken advantage of the development of nanoplatforms capable of selectively accumulating diagnostic agents into non-healthy sites. The fi rst volume “Nanoplatforms in Drug Delivery” of the book series “Nanotechnology and Drug Delivery” focused on the study of the representative physicochemical engineering approaches to the formulation of drug nanocarriers. In that book, special emphasis was given to those materials mainly used in nanoplatform formulation. The second volume “Nano-Engineering Strategies and Nanomedicines against Severe Diseases” of the series of two volumes analyzes in depth the possibilities coming from the application of nanotechnology to the formulation of nanoplatforms to be administered through a route of drug administration, i.e., oral, dental, topical and transdermal, pulmonary and nasal, ocular and otic, vaginal, and even brain delivery and targeting. Special emphasis is given to the main aspects being considered when engineering a nanomedicine for a given route of administration, e.g., to the barriers that the drug nanocarrier will face before getting access to the bloodstream. The second part of the book will proportionate an updated vision of nanomedicines under clinical use or under development against severe diseases, i.e., cancer, cardiovascular diseases, neurodegenerative disorders, infectious diseases, chronic inflammatory diseases, and metabolic diseases. As a complementary image to the problem of the selective delivery of therapeutic agents, a chapter is focused on the use of nanoplatforms as carriers of genetic materials. Finally, attention is further given to the revolutionary concept of nanotheranosis, involving the design of nanoparticulate structures for a combined disease diagnosis and treatment. Such a promising approach was initially ascribed to the idea of image- guided drug delivery, but it is expected to be the defi nitive move toward the development of personalized medicines. Chapter 1 (Emerging Technologies of Polymers for Nanomedicine Applications) focuses on a critical analysis of the use of polymeric viii Nanotechnology and Drug Delivery: Volume 2 nanomaterials in the development of drug delivery systems. Key properties of polymers to be considered and advances made in the fi eld of drug delivery are brilliantly described by Prof. Souto and co-workers. The analysis of key aspects in the engineering of a nanomedicine to be administered orally is discussed in Chapter 2 (Nanotechnology for Oral Drug Delivery and Targeting, by the research group of Prof. Pinto Reis). Strategies are described to maximize drug delivery by the oral route and, therefore, drug bioavailability. Additionally, this contribution critically analyzes the challenges/opportunities found in the oral route, the breakthroughs in nanomedicine formulation, and the strategies being proposed to optimize drug delivery. The rapidly emerging fi eld of nanomedicine in dentistry is updated by Prof. Nguyen and co-authors (Chapter 3: Nanoparticulate Systems for Dental Drug Delivery). Special focus is given to liposomes, while the potential of other nanomaterials for use as dental drug delivery systems is also analyzed by the authors. In another interesting contribution, recent progress, benefi ts, practical limitations, and toxicity issues coming from the application of nanotechnology to transdermal and topical drug delivery are critically described by the research group of Prof. Roberts (Chapter 4: Nanotechnology for Topical and Transdermal Drug Delivery and Targeting). Special insight concerning the use of deformable liposomes and enhanced delivery devices to improve transdermal delivery of therapeutic molecules. The pulmonary route of drug administration is also taking advantage on the engineering of nanoparticulate systems. Chapter 5 (Nanotechnology for Pulmonary and Nasal Drug Delivery) describes the engineering technologies involving not only traditional techniques but additionally more innovative processes to produce nanoparticles with a defi ned physical chemistry assuring an effi cient nasal or pulmonary deposition. Prof. Williams III and his colleague further discuss the pulmonary and nasal physiologies correlated to particle deposition and absorption, and the clinical considerations of pulmonary and nasal delivery of nanoparticulate systems. A complementary contribution facilitating a detailed vision of the current state of the art in nanoparticulate- based pulmonary drug delivery has been written by Prof. Souto and co- authors (Chapter 6: Lipid Nanoplatforms for Pulmonary Drug Delivery). Their contribution is devoted to the in-depth study of novel therapeutic micro/nanostrategies generating satisfactory outcomes against some common diseases that affect the respiratory apparatus. Commonly used aerosol types and administration of micro/nanocarriers are analyzed, including their properties, applications, and toxicities. Prof. Attama and co-workers (Chapter 7: Nanotechnology for Ocular and Otic Drug Delivery and Targeting) study the representative nanoparticulate structures for ocular/otic drug delivery and targeting that are overcoming the inherent limitations of conventional medicines. Current developments and applications to evade static and dynamic barriers associated with these organs are explored in depth. Nanoparticle-based approaches to the vaginal route of drug administration are updated in Chapter 8 (Nanotechnology for Vaginal