- Email: [email protected]
Advanced drug delivery in the post-genomic era
Advanced Drug Delivery Reviews 61 (2009) 1389–1390
Contents lists available at ScienceDirect
Advanced Drug Delivery Reviews j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / a d d r
Editorial
Advanced drug delivery in the post-genomic era
I wish to begin this editorial by paying a belated tribute to the late Dr. Jorge Heller, a legend in controlled drug delivery in the recent past. Dr. Heller was one of the early advocates of using biodegradable polymers as a versatile drug delivery platform. His unwavering commitment to a singular research focus in poly(ortho esters) in his entire career is an inspiration for all of us. His leadership as conference program chair, journal editor, and society president was instrumental in creating a culture in the controlled release community that values diversity and quality, attributes that are pivotal in the spectacular rise in the scientific stature of this community today. On behalf of the journal, I also wish to acknowledge the exemplary service of Dr. Mark Gumbleton as Executive Editor for the past seven years. He owed his vintage effectiveness to a dynamic blend of eternal curiosity, scientific charisma, accountability, commitment to quality, willingness to be criticized as well as to be critical. He was an excellent team player who had made significant personal sacrifices on several occasions for the benefit of the ADDR readership. In fact, Mark was an advocate for this annual issue #15 comprised of standalone reviews or perspectives on emerging concepts/technologies. He followed through by volunteering to coordinate the planning of this issue in the past three years. This is not an easy task, as I found out in taking on that role this year. Advanced Drug Delivery Reviews (ADDR) is recognized internationally for its timely quality reviews and perspectives at the forefront of drug delivery. This is the outcome of the coming together of five Executive Editors from diverse scientific backgrounds to press towards a common goal for ADDR. The Executive Editors play a central role in developing theme topics, recruiting theme editors, and serving as their advocate in quality assurance. Effective on January 1, 2010. Dr. Vincent Rotello and Dr. Hak-Kim Chan will join the editorial team presently comprised of Dr. Hamid Ghanderhari (University of Utah), Dr. Sarah Hamm-Alvarez (University of Southern California), and Dr. Yoshinobu Takakura (Kyoto University). Vincent is Charles A. Goessmann Professor of Chemistry at the University of Massachusetts (http://www.umass.edu/rotellogroup/). He is known internationally for his research on applying innovative chemistry to engineer functional nanomaterials for drug and gene delivery and diagnostic sensing. Hak-Kim, known as Kim among friends, is Professor of Pharmaceutics at the University of Sydney (http://www. pharm.usyd.edu.au/about/people/chank.shtml). He is a world leader in pulmonary drug delivery with special expertise in particle engineering, formulation design, and imaging. More details on both editors will be available in the earliest possible issue of ADDR. The completion of the Human Genome Project in April 2003 has ushered in a new era of disease intervention at the molecular rather than the symptomatic level. This paradigm shift has provided an impetus for broadening the traditional definition of drug delivery and for formalizing interdisciplinary research as a necessity to successfully 0169-409X/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.addr.2009.10.001
design and develop innovative drug delivery systems to meet the higher expectation in their performance. The 2009 volume of ADDR was planned to provide a snapshot of the transformation in drug delivery that has already begun. What is noteworthy is early acceptance of including cost-effectiveness analysis in decision making on the development of new drug delivery technologies. Consequently, drug delivery advances in this era will be shaped not only by scientific and technological advances but also by the anticipated extent of access to the technology by potential users. Worldwide, the incidence of neurodegenerative disease and cancer is on the rise and the search for effective therapeutic will no doubt top the list of priorities. Towards that end, the spot light will be on the mitochondria and on ways to best reach this organelle in order to preempt oxidative stress mediated by free radicals. The theme issues on “Mitochondrial Medicine (Part II)” and on “Controlling Oxidative Stress” serve to point out the salient features of the mitochondria, free radicals, and oxidative stress that should be considered in developing strategies for targeting drugs to this organelle. Opportunities for future advances in drug delivery are plenty. These are aligned with gene regulation, woman (or other subpopulation) health, preventive health (e.g., vaccination), and regenerative medicine. Each possibility is the subject of a specific theme issue in this volume. The main challenge that cuts across all cases is invariably the development of methodologies to enhance the efficiency of passage of the new therapeutics, typically products of biotechnology, across the plasma membrane of cells and their subsequent navigation to the subcellular destination. There is a wealth of information on several innovative approaches in two theme issues entitled, respectively, “Optimizing the Future for Biotechnology Therapeutics: The Key Role of Protein Engineering” (edited by Camarero) and “Polymer Therapeutics: Clinical Applications and Challenges for Development” (coedited by Vicent. Ringsdorf, and Duncan). The latter theme issue is an excellent reminder of the long development time required to meet the stringent standards drug regulatory agencies set for innovative products. I wish to congratulate Professor Ruth Duncan for her two-decade long leadership and perseverance in championing the clinical applications of polymer therapeutics. Nano systems have been featured in every volume of ADDR since 1980, but the pace of research did not pick up in ernst until 2000. The issue on “Drug and Gene Delivery to Mucosal Tissues: The Mucus Barrier” by Hanes and Demeester provides a critical analysis of ways to control the interaction between nanosystems and the underlying mucus milieu. The effectiveness of this approach in nasal and pulmonary delivery is described. There is also an excellent account on how cystic fibrosis brings about changes in the mucus coat in the respiratory epithelia that interferes with the efficiency of nanosystem as a drug carrier.
1390
Editorial
An important transformational change in drug delivery research is advancing the time table of assessing the regulatory/commercial viability of drug delivery innovations. This is exemplified in the theme issue on “Identifying and Assessing Biomaterial Nanotoxicity in Translational Resaerch for Clinical Development.” Furgeson and Dobrovoskaia, co-editors of this theme issue, presented the framework to evaluate nanotoxicity and pointed out the dearth of experimental models and tools required to generate clinically relevant information. This could be a welcomed change in the philosophy of new drug discovery and development, and wider acceptance of this integrated approach in future drug development should be encouraged. The issue on the human ABC transporter has illuminated one aspect by which polymorphism in an endogenous transporter can add to the complexity of the epithelial transporter barrier. It is a thought provoking issue that points to the advances that have yet to be made before routine personalized medicine can be a reality. This sentiment is also shared by another theme issue on “Recent Advances in Cancer Chemotherapy: Current Strategies, Pharmacokinetics, Pharmacogenomics” edited by Nishiyama and Eguchi. Here a case was made for the value added by targeted therapeutics in the management of some cancers. A few remarks on this final issue of standalone articles are in order. The four topics featured were selected from a pool of 19 topics submitted to the editorial office for prescreening. The topic on “Molecular and magnetic resonance imaging” serves as an update on the increased acceptance of imaging to guide the development of delivery systems as well as to monitor the efficiency of delivery. The authors presented an impartial view on the incremental progress that has been made and emphatically indicated the long road ahead with many more obstacles yet to be overcome. A long-cherished goal in drug delivery is access to intelligent systems capable of sensing and responding to stimuli unique to a disease state in a given patient. Progress in this exciting field is summarized succinctly in the paper by Caldorera-Moore and Peppas entitled “Micro- and Nanotechnologies for Intelligent and Responsive Biomaterial-based Medical Systems.” The convergence of sophisticated micro- and nanofabrication techniques with refinements in the design of environmentally sensitive materials bodes well for making personalized medicine a therapeutic reality. The other two topics deal with a modern view on excipients, an aspect of formulation design that is gaining the attention by regulatory agencies. At issue is the long-term safety of excipients in oral formulations. The article by Maher et al. documents the approach this team of investigators undertook to manage the safety risk of using
Na caprate, a medium chain fatty acid that already has been approved as a food additive, to increase epithelial permeability. In order to use this compound routinely for enhancing the oral bioavailability of water-soluble drug candidates with poor membrane permeability, the so-called Class III drugs in the Biopharmaceutic Classification System, there must be transparency in addressing long-term safety issues. The companion article on squalene by Reddy and Couvreur introduces a potential complication in its use as an excipient to stabilize emulsions. Squalene is a lipid belonging to the terpenoid family and a precursor of cholesterol biosynthesis. Despite its apparent inertness, squalene exhibits weak chemopreventive and immunoadjuvant activities. The lesson to learn is that the time is ripe to screen for possible effects of existing excipients on cellular biochemistry and pharmacology. It is conceivable that, as a result, the prevailing definition of generic drug products may need to be updated as mandated by the new knowledge on possible effect excipients may exert on epithelial permeability and cellular homeostasis. Looking ahead, drug delivery is destined to make an impact in global health and in health care reform. In order to meet this challenge, an integrated approach and greater willingness to share information must be considered against the backdrop of an avalanche of new knowledge on the molecular and genetic origin of disease. It is the longstanding mission of Advanced Drug Delivery Reviews to feature the lessons learned (triumphs as well as disappointments) in pursuit of innovative drug delivery systems that draw on the shared vision and synergy of a community of independent investigators. I am pleased that the 2009 volume of ADDR has provided an excellent snapshot on the path-finding research in advanced molecular drug delivery under the broad umbrella of system biology. I thank the theme editors for their effort to showcase the cutting edge science and thank the Executive Editors for recruiting an excellent mix of experienced and up-and-coming scientific leaders to develop these themes. Their collective commitment to quality is much appreciated. Vincent H.L. Lee (Editor-in-Chief) Hong Kong SAR E-mail address: [email protected]
Contents lists available at ScienceDirect
Advanced Drug Delivery Reviews j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / a d d r
Editorial
Advanced drug delivery in the post-genomic era
I wish to begin this editorial by paying a belated tribute to the late Dr. Jorge Heller, a legend in controlled drug delivery in the recent past. Dr. Heller was one of the early advocates of using biodegradable polymers as a versatile drug delivery platform. His unwavering commitment to a singular research focus in poly(ortho esters) in his entire career is an inspiration for all of us. His leadership as conference program chair, journal editor, and society president was instrumental in creating a culture in the controlled release community that values diversity and quality, attributes that are pivotal in the spectacular rise in the scientific stature of this community today. On behalf of the journal, I also wish to acknowledge the exemplary service of Dr. Mark Gumbleton as Executive Editor for the past seven years. He owed his vintage effectiveness to a dynamic blend of eternal curiosity, scientific charisma, accountability, commitment to quality, willingness to be criticized as well as to be critical. He was an excellent team player who had made significant personal sacrifices on several occasions for the benefit of the ADDR readership. In fact, Mark was an advocate for this annual issue #15 comprised of standalone reviews or perspectives on emerging concepts/technologies. He followed through by volunteering to coordinate the planning of this issue in the past three years. This is not an easy task, as I found out in taking on that role this year. Advanced Drug Delivery Reviews (ADDR) is recognized internationally for its timely quality reviews and perspectives at the forefront of drug delivery. This is the outcome of the coming together of five Executive Editors from diverse scientific backgrounds to press towards a common goal for ADDR. The Executive Editors play a central role in developing theme topics, recruiting theme editors, and serving as their advocate in quality assurance. Effective on January 1, 2010. Dr. Vincent Rotello and Dr. Hak-Kim Chan will join the editorial team presently comprised of Dr. Hamid Ghanderhari (University of Utah), Dr. Sarah Hamm-Alvarez (University of Southern California), and Dr. Yoshinobu Takakura (Kyoto University). Vincent is Charles A. Goessmann Professor of Chemistry at the University of Massachusetts (http://www.umass.edu/rotellogroup/). He is known internationally for his research on applying innovative chemistry to engineer functional nanomaterials for drug and gene delivery and diagnostic sensing. Hak-Kim, known as Kim among friends, is Professor of Pharmaceutics at the University of Sydney (http://www. pharm.usyd.edu.au/about/people/chank.shtml). He is a world leader in pulmonary drug delivery with special expertise in particle engineering, formulation design, and imaging. More details on both editors will be available in the earliest possible issue of ADDR. The completion of the Human Genome Project in April 2003 has ushered in a new era of disease intervention at the molecular rather than the symptomatic level. This paradigm shift has provided an impetus for broadening the traditional definition of drug delivery and for formalizing interdisciplinary research as a necessity to successfully 0169-409X/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.addr.2009.10.001
design and develop innovative drug delivery systems to meet the higher expectation in their performance. The 2009 volume of ADDR was planned to provide a snapshot of the transformation in drug delivery that has already begun. What is noteworthy is early acceptance of including cost-effectiveness analysis in decision making on the development of new drug delivery technologies. Consequently, drug delivery advances in this era will be shaped not only by scientific and technological advances but also by the anticipated extent of access to the technology by potential users. Worldwide, the incidence of neurodegenerative disease and cancer is on the rise and the search for effective therapeutic will no doubt top the list of priorities. Towards that end, the spot light will be on the mitochondria and on ways to best reach this organelle in order to preempt oxidative stress mediated by free radicals. The theme issues on “Mitochondrial Medicine (Part II)” and on “Controlling Oxidative Stress” serve to point out the salient features of the mitochondria, free radicals, and oxidative stress that should be considered in developing strategies for targeting drugs to this organelle. Opportunities for future advances in drug delivery are plenty. These are aligned with gene regulation, woman (or other subpopulation) health, preventive health (e.g., vaccination), and regenerative medicine. Each possibility is the subject of a specific theme issue in this volume. The main challenge that cuts across all cases is invariably the development of methodologies to enhance the efficiency of passage of the new therapeutics, typically products of biotechnology, across the plasma membrane of cells and their subsequent navigation to the subcellular destination. There is a wealth of information on several innovative approaches in two theme issues entitled, respectively, “Optimizing the Future for Biotechnology Therapeutics: The Key Role of Protein Engineering” (edited by Camarero) and “Polymer Therapeutics: Clinical Applications and Challenges for Development” (coedited by Vicent. Ringsdorf, and Duncan). The latter theme issue is an excellent reminder of the long development time required to meet the stringent standards drug regulatory agencies set for innovative products. I wish to congratulate Professor Ruth Duncan for her two-decade long leadership and perseverance in championing the clinical applications of polymer therapeutics. Nano systems have been featured in every volume of ADDR since 1980, but the pace of research did not pick up in ernst until 2000. The issue on “Drug and Gene Delivery to Mucosal Tissues: The Mucus Barrier” by Hanes and Demeester provides a critical analysis of ways to control the interaction between nanosystems and the underlying mucus milieu. The effectiveness of this approach in nasal and pulmonary delivery is described. There is also an excellent account on how cystic fibrosis brings about changes in the mucus coat in the respiratory epithelia that interferes with the efficiency of nanosystem as a drug carrier.
1390
Editorial
An important transformational change in drug delivery research is advancing the time table of assessing the regulatory/commercial viability of drug delivery innovations. This is exemplified in the theme issue on “Identifying and Assessing Biomaterial Nanotoxicity in Translational Resaerch for Clinical Development.” Furgeson and Dobrovoskaia, co-editors of this theme issue, presented the framework to evaluate nanotoxicity and pointed out the dearth of experimental models and tools required to generate clinically relevant information. This could be a welcomed change in the philosophy of new drug discovery and development, and wider acceptance of this integrated approach in future drug development should be encouraged. The issue on the human ABC transporter has illuminated one aspect by which polymorphism in an endogenous transporter can add to the complexity of the epithelial transporter barrier. It is a thought provoking issue that points to the advances that have yet to be made before routine personalized medicine can be a reality. This sentiment is also shared by another theme issue on “Recent Advances in Cancer Chemotherapy: Current Strategies, Pharmacokinetics, Pharmacogenomics” edited by Nishiyama and Eguchi. Here a case was made for the value added by targeted therapeutics in the management of some cancers. A few remarks on this final issue of standalone articles are in order. The four topics featured were selected from a pool of 19 topics submitted to the editorial office for prescreening. The topic on “Molecular and magnetic resonance imaging” serves as an update on the increased acceptance of imaging to guide the development of delivery systems as well as to monitor the efficiency of delivery. The authors presented an impartial view on the incremental progress that has been made and emphatically indicated the long road ahead with many more obstacles yet to be overcome. A long-cherished goal in drug delivery is access to intelligent systems capable of sensing and responding to stimuli unique to a disease state in a given patient. Progress in this exciting field is summarized succinctly in the paper by Caldorera-Moore and Peppas entitled “Micro- and Nanotechnologies for Intelligent and Responsive Biomaterial-based Medical Systems.” The convergence of sophisticated micro- and nanofabrication techniques with refinements in the design of environmentally sensitive materials bodes well for making personalized medicine a therapeutic reality. The other two topics deal with a modern view on excipients, an aspect of formulation design that is gaining the attention by regulatory agencies. At issue is the long-term safety of excipients in oral formulations. The article by Maher et al. documents the approach this team of investigators undertook to manage the safety risk of using
Na caprate, a medium chain fatty acid that already has been approved as a food additive, to increase epithelial permeability. In order to use this compound routinely for enhancing the oral bioavailability of water-soluble drug candidates with poor membrane permeability, the so-called Class III drugs in the Biopharmaceutic Classification System, there must be transparency in addressing long-term safety issues. The companion article on squalene by Reddy and Couvreur introduces a potential complication in its use as an excipient to stabilize emulsions. Squalene is a lipid belonging to the terpenoid family and a precursor of cholesterol biosynthesis. Despite its apparent inertness, squalene exhibits weak chemopreventive and immunoadjuvant activities. The lesson to learn is that the time is ripe to screen for possible effects of existing excipients on cellular biochemistry and pharmacology. It is conceivable that, as a result, the prevailing definition of generic drug products may need to be updated as mandated by the new knowledge on possible effect excipients may exert on epithelial permeability and cellular homeostasis. Looking ahead, drug delivery is destined to make an impact in global health and in health care reform. In order to meet this challenge, an integrated approach and greater willingness to share information must be considered against the backdrop of an avalanche of new knowledge on the molecular and genetic origin of disease. It is the longstanding mission of Advanced Drug Delivery Reviews to feature the lessons learned (triumphs as well as disappointments) in pursuit of innovative drug delivery systems that draw on the shared vision and synergy of a community of independent investigators. I am pleased that the 2009 volume of ADDR has provided an excellent snapshot on the path-finding research in advanced molecular drug delivery under the broad umbrella of system biology. I thank the theme editors for their effort to showcase the cutting edge science and thank the Executive Editors for recruiting an excellent mix of experienced and up-and-coming scientific leaders to develop these themes. Their collective commitment to quality is much appreciated. Vincent H.L. Lee (Editor-in-Chief) Hong Kong SAR E-mail address: [email protected]