A prerequisite for the efficacy of any cancer drug is that it reaches the tumor in therapeutic concentrations. This is difficult to accomplish in most systemic solid tumors because of factors such as variable hypoxia, intratumoral pressure gradients,
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In recent years, there has been a considerable interest in the development of novel drug delivery systems using nanotechnology. Nanoparticles represent a promising drug delivery system of controlled and targeted release. In this context, nanosuspensi
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Pharm Res (2013) 30:2427–2428 DOI 10.1007/s11095-013-1148-7
Brain Drug Delivery Systems Xinguo Jiang
Published online: 7 August 2013 # Springer Science+Business Media New York 2013
At present, major central nervous system (CNS) disorders, including neurodegenerative diseases, cerebrovascular diseases, and brain tumors, are serious threats to human health due to the aging of the general population. For example, more than 24 million people worldwide are currently suffering from Alzheimer’s disease, and approximately 15 million injuries and 5 million deaths were caused by stroke each year. However, drug delivery for the treatment of these brain diseases is far from efficient. The main obstacle for brain drug delivery is the blood–brain barrier (BBB), which is composed of polarized endothelial cells, astrocytes, microglial cells, and pericytes, and which separates the blood from the underlying brain cells, providing protection to neurons and preserving CNS homeostasis. Essentially, nearly 100% of large-molecule drugs and >98% of small-molecule drugs do not penetrate the BBB. Nanotechnology-based drug delivery systems could bring hope to brain drug delivery for the treatment of brain diseases and have become a hot topic in the field of drug delivery. Tremendous efforts have been made in the treatment of CNS disorders, and some impressive developments have been achieved. The aim of this theme issue is to address the latest important developments of brain drug delivery systems in the diagnosis and treatment of Alzheimer’s disease, Parkinson’s disease, stroke, and brain tumors. It contains six review articles and seven research papers written by eminent experts from Europe, the United States, and Asia. In this theme
X. Jiang (*) Key Laboratory of Smart Drug Delivery, Ministry of Education School of Pharmacy, Fudan University 826 Zhangheng Road, Shanghai 201203, People’s Republic of China e-mail: [email protected]
issue, readers will find a general review of nanotherapeutics for major diseases in central nervous systems (Jiang et al.). Considering that brain drug delivery strategies could be adapted according to the unique pathological features of different brain diseases, more specialized reviews in nanotechnology-based drug delivery systems for the diagnosis and treatment of neurodegenerative diseases (BozdağPehlivan), brain tumors (Yang et al.), and ischemic stroke (Lee et al.) are also provided. For instance, recent work indicates that the perturbation of axonal transport is an early marker in the pathological process of many neurodegenerative diseases. Thus, developing novel therapeutics targeting this early precursor in neuronal dysfunction is critical for the treatment of neurodegenerative diseases. The review by Gunawardena discusses the potential of a novel nanotechnology-based approach to targeting this early defect in neurodegenerative diseases to maximize the therapeutic effects. As a noninvasive way to deliver drugs to the CNS, intranasal delivery offers a direct nose-to-brain pathway bypassing the BBB and represents a promising therapeutic strategy for the treatment of CNS diseases (Benedict et al.). Novel strategies for brain drug delivery are also presented in original papers of this theme issue. Jiang et al. designed angiopep-conjugated nanoparticles for the targeted longterm gene therapy of Parkinson’s disease, and Peura et al. explored a large amino acid transporter 1-based strategy for the brain delivery of dopamine. A fatty acid-based strategy was used for efficient brain gene delivery (Lu et al.), and small-interfering RNA (siRNA) was delivered into neurons to knock down protein expression by means of a dendrimer (Cena et al.). In addition to the above-mentioned receptormediated, carrier-mediated approaches, the rational design of nanotechnology-based brain drug delivery system including the optimization of particle size and surface modification
(Feng et al.), the multivalent effect of targeting moieties (Li et al.), and small-molecule enhancers such as borneol (Wang et al.) to up-regulate the BBB permeability of nanoparticles are also discussed. After exploring these novel strategies and the latest important developments of brain drug delivery systems provided in each paper of this theme issue, the reader is encouraged to foster innovative crossdisciplinary thinking and open up new avenues in designing effective brain drug delivery systems for treating brain diseases. The guest editor and all authors of this thematic issue are deeply grateful to special features editor Ram I. Mahato and editorial assistant Ms. Rachel D. Lucke for their valuable suggestions and editorial board for their foresight in encouraging an issue on this topic.
Xinguo Jiang is a professor in the School of Pharmacy, Fudan University, an Academic Leader of the National Key Discipline of Pharmaceutics, and Chief Scientist of a national key basic research program. As a pharmaceutics scientist, Professor Jiang mainly focuses on the development of novel pharmaceuticals, especially nanotechnology-based drug delivery systems. He has owned 15 patents and two new drug approvals. He is the editor of three books and nearly 110 peer-reviewed articles published in the drug delivery field.