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Advanced Drug Delivery Reviews (v.65, #1)
No Title
by Vincent H.L. Lee Theme Editor; Hamidreza Ghandehari Theme Editor (pp. 1-2).
No Title
by Vincent H.L. Lee Theme Editor; Hamidreza Ghandehari Theme Editor (pp. 1-2).
Perspective from the founding editors
by Rudy Juliano (Theme Editor); George Poste (Theme Editor); Eric Tomlinson (Theme Editor) (pp. 3-4).
Drug delivery; Molecular diversity; Modern biology; Interdisciplinary; Chronic disease; Cost‐effectiveness
Perspective from the founding editors
by Rudy Juliano (Theme Editor); George Poste (Theme Editor); Eric Tomlinson (Theme Editor) (pp. 3-4).
Drug delivery; Molecular diversity; Modern biology; Interdisciplinary; Chronic disease; Cost‐effectiveness
Historical perspective on advanced drug delivery: How engineering design and mathematical modeling helped the field mature
by Nicholas A. Peppas (pp. 5-9).
We review the early developments in drug delivery from 1960 to 1990 with emphasis on the fundamental aspects of the field and how they shaped the collaboration of pharmaceutical scientists, chemists, biologists, engineers and medical scientists towards the development of advanced drug delivery systems. Emphasis is given on the advances of biomaterials as drug delivery agents and on the use of design equations and mathematical modeling to achieve a wide range of successful systems.
Keywords: Drug delivery; Controlled release; Nanotechnology; Mathematical modeling; Diffusion-controlled systems; Matrix systems; Reservoir systems; Biodegradable systems; Swellable systems
Historical perspective on advanced drug delivery: How engineering design and mathematical modeling helped the field mature
by Nicholas A. Peppas (pp. 5-9).
We review the early developments in drug delivery from 1960 to 1990 with emphasis on the fundamental aspects of the field and how they shaped the collaboration of pharmaceutical scientists, chemists, biologists, engineers and medical scientists towards the development of advanced drug delivery systems. Emphasis is given on the advances of biomaterials as drug delivery agents and on the use of design equations and mathematical modeling to achieve a wide range of successful systems.
Keywords: Drug delivery; Controlled release; Nanotechnology; Mathematical modeling; Diffusion-controlled systems; Matrix systems; Reservoir systems; Biodegradable systems; Swellable systems
Stimuli-responsive polymers: Biomedical applications and challenges for clinical translation
by Allan S. Hoffman (pp. 10-16).
Over the past 25years many interesting biomedical uses have been proposed for stimuli-responsive polymers, including uses in diagnostics, drug delivery, tissue engineering (regenerative medicine), and cell culture. This article briefly overviews the field of stimuli-responsive polymers and describes some of the most successful biomedical applications to date of such “smart” polymers. Other interesting potential applications are also discussed. The major barriers to future clinical translation of smart polymers are also critically discussed.Display Omitted
Keywords: Stimuli-responsive polymers; Biomedical applications and challenges for clinical translation
Stimuli-responsive polymers: Biomedical applications and challenges for clinical translation
by Allan S. Hoffman (pp. 10-16).
Over the past 25years many interesting biomedical uses have been proposed for stimuli-responsive polymers, including uses in diagnostics, drug delivery, tissue engineering (regenerative medicine), and cell culture. This article briefly overviews the field of stimuli-responsive polymers and describes some of the most successful biomedical applications to date of such “smart” polymers. Other interesting potential applications are also discussed. The major barriers to future clinical translation of smart polymers are also critically discussed.Display Omitted
Keywords: Stimuli-responsive polymers; Biomedical applications and challenges for clinical translation
Hydrogels for delivery of bioactive agents: A historical perspective
by Sang Cheon Lee; Il Keun Kwon; Kinam Park (pp. 17-20).
Since 1960 when the history of modern hydrogels began significant progress has been made in the field of controlled drug delivery. In particular, recent advances in the so-called smart hydrogels have made it possible to design highly sophisticated formulations, e.g., self-regulated drug delivery systems. Despite intensive efforts, clinical applications of smart hydrogels have been limited. Smart hydrogels need to be even smarter to execute functions necessary for achieving desired clinical functions. It is necessary to develop novel hydrogels that meet the requirements of the intended, specific applications, rather than finding applications of newly developed hydrogels. Furthermore, developing smarter hydrogels that can mimic natural systems is necessary, but the fundamental differences between natural and synthetic systems need to be understood. Such understanding will allow us to develop novel hydrogels with the new, multiple functions that we are looking for.Display Omitted
Keywords: Hydrogels; Smart hydrogels; Self-regulated drug delivery; Clinical applications; Mimicking natural systems
Hydrogels for delivery of bioactive agents: A historical perspective
by Sang Cheon Lee; Il Keun Kwon; Kinam Park (pp. 17-20).
Since 1960 when the history of modern hydrogels began significant progress has been made in the field of controlled drug delivery. In particular, recent advances in the so-called smart hydrogels have made it possible to design highly sophisticated formulations, e.g., self-regulated drug delivery systems. Despite intensive efforts, clinical applications of smart hydrogels have been limited. Smart hydrogels need to be even smarter to execute functions necessary for achieving desired clinical functions. It is necessary to develop novel hydrogels that meet the requirements of the intended, specific applications, rather than finding applications of newly developed hydrogels. Furthermore, developing smarter hydrogels that can mimic natural systems is necessary, but the fundamental differences between natural and synthetic systems need to be understood. Such understanding will allow us to develop novel hydrogels with the new, multiple functions that we are looking for.Display Omitted
Keywords: Hydrogels; Smart hydrogels; Self-regulated drug delivery; Clinical applications; Mimicking natural systems
Nanoparticles in drug delivery: Past, present and future
by P. Couvreur (pp. 21-23).
This opinion paper relates how nanoparticles were discovered in the seventies and how the development of biodegradable materials and nanoparticle surface functionalization has allowed new treatment strategies. The reasons why only very few nanoparticle-based medicines are on the market or in late clinical trials are discussed and some new approaches are identified. Future challenges in the nanoparticle field are also identified.Display Omitted
Keywords: Nanoparticles; Nanospheres; Nanocapsules; Polymers; Drug loading; Intracellular delivery; Drug targeting; Nanotheragnostics; Opsonization; Biodegradability; Cancer resistance
Nanoparticles in drug delivery: Past, present and future
by P. Couvreur (pp. 21-23).
This opinion paper relates how nanoparticles were discovered in the seventies and how the development of biodegradable materials and nanoparticle surface functionalization has allowed new treatment strategies. The reasons why only very few nanoparticle-based medicines are on the market or in late clinical trials are discussed and some new approaches are identified. Future challenges in the nanoparticle field are also identified.Display Omitted
Keywords: Nanoparticles; Nanospheres; Nanocapsules; Polymers; Drug loading; Intracellular delivery; Drug targeting; Nanotheragnostics; Opsonization; Biodegradability; Cancer resistance
Immunoconjugates and long circulating systems: Origins, current state of the art and future directions
by Alexander Koshkaryev; Rupa Sawant; Madhura Deshpande; Vladimir Torchilin (pp. 24-35).
Significant progress has been made recently in the area of immunoconjugated drugs and drug delivery systems (DDS). The immuno-modification of either the drug or DDS has proven to be a very promising approach that has significantly improved the targeted accumulation in pathological sites while decreasing its undesirable side effects in healthy tissues. The arrangement for both prolonged life in the circulation and specific target recognition represents another potent strategy in the development of immuno-targeted systems. The longevity of immuno-targeted DDS such as immunoliposomes and immunomicelles improves their targetability even in the presence of the additional passive accumulation in areas with a compromised vasculature. The added use of the immuno-targeted systems takes advantage of the specific microenvironment of pathological sites including lowered pH, increased temperature, and variation in the enzymatic activity. “Smart” stimulus-responsive systems combine different valuable functionalities including PEG-protection, targeting antibody, cell-penetration, and stimulus-sensitive functions.In this review we examined the evolution, current status and future directions in the area of therapeutical immunoconjugates and long-circulating immuno-targeted DDS.Display Omitted
Keywords: Antibody; Immunoconjugation; Long-circulating systems; PEGylation; Immunoliposomes; Immunomicelles
Immunoconjugates and long circulating systems: Origins, current state of the art and future directions
by Alexander Koshkaryev; Rupa Sawant; Madhura Deshpande; Vladimir Torchilin (pp. 24-35).
Significant progress has been made recently in the area of immunoconjugated drugs and drug delivery systems (DDS). The immuno-modification of either the drug or DDS has proven to be a very promising approach that has significantly improved the targeted accumulation in pathological sites while decreasing its undesirable side effects in healthy tissues. The arrangement for both prolonged life in the circulation and specific target recognition represents another potent strategy in the development of immuno-targeted systems. The longevity of immuno-targeted DDS such as immunoliposomes and immunomicelles improves their targetability even in the presence of the additional passive accumulation in areas with a compromised vasculature. The added use of the immuno-targeted systems takes advantage of the specific microenvironment of pathological sites including lowered pH, increased temperature, and variation in the enzymatic activity. “Smart” stimulus-responsive systems combine different valuable functionalities including PEG-protection, targeting antibody, cell-penetration, and stimulus-sensitive functions.In this review we examined the evolution, current status and future directions in the area of therapeutical immunoconjugates and long-circulating immuno-targeted DDS.Display Omitted
Keywords: Antibody; Immunoconjugation; Long-circulating systems; PEGylation; Immunoliposomes; Immunomicelles
Liposomal drug delivery systems: From concept to clinical applications
by Theresa M. Allen; Pieter R. Cullis (pp. 36-48).
The first closed bilayer phospholipid systems, called liposomes, were described in 1965 and soon were proposed as drug delivery systems. The pioneering work of countless liposome researchers over almost 5 decades led to the development of important technical advances such as remote drug loading, extrusion for homogeneous size, long-circulating (PEGylated) liposomes, triggered release liposomes, liposomes containing nucleic acid polymers, ligand-targeted liposomes and liposomes containing combinations of drugs. These advances have led to numerous clinical trials in such diverse areas as the delivery of anti-cancer, anti-fungal and antibiotic drugs, the delivery of gene medicines, and the delivery of anesthetics and anti-inflammatory drugs. A number of liposomes (lipidic nanoparticles) are on the market, and many more are in the pipeline. Lipidic nanoparticles are the first nanomedicine delivery system to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance. We can look forward to many more clinical products in the future.Display Omitted
Keywords: Liposome; Lipidic nanoparticle; Polyethylene glycol; Anti-cancer drugs; siRNA; Pharmacokinetics; Biodistribution; Ligand-targeted
Liposomal drug delivery systems: From concept to clinical applications
by Theresa M. Allen; Pieter R. Cullis (pp. 36-48).
The first closed bilayer phospholipid systems, called liposomes, were described in 1965 and soon were proposed as drug delivery systems. The pioneering work of countless liposome researchers over almost 5 decades led to the development of important technical advances such as remote drug loading, extrusion for homogeneous size, long-circulating (PEGylated) liposomes, triggered release liposomes, liposomes containing nucleic acid polymers, ligand-targeted liposomes and liposomes containing combinations of drugs. These advances have led to numerous clinical trials in such diverse areas as the delivery of anti-cancer, anti-fungal and antibiotic drugs, the delivery of gene medicines, and the delivery of anesthetics and anti-inflammatory drugs. A number of liposomes (lipidic nanoparticles) are on the market, and many more are in the pipeline. Lipidic nanoparticles are the first nanomedicine delivery system to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance. We can look forward to many more clinical products in the future.Display Omitted
Keywords: Liposome; Lipidic nanoparticle; Polyethylene glycol; Anti-cancer drugs; siRNA; Pharmacokinetics; Biodistribution; Ligand-targeted
Polymer–drug conjugates: Origins, progress to date and future directions
by Kopecek Jindřich Kopeček (pp. 49-59).
This overview focuses on bioconjugates of water-soluble polymers with low molecular weight drugs and proteins. After a short discussion of the origins of the field, the state-of-the-art is reviewed. Then research directions needed for the acceleration of the translation of nanomedicines into the clinic are outlined. Two most important directions, synthesis of backbone degradable polymer carriers and drug-free macromolecular therapeutics, a new paradigm in drug delivery, are discussed in detail. Finally, the future perspectives of the field are briefly discussed.Display Omitted
Keywords: Nanomedicine; Bioconjugates; Cancer; Degradable spacers; Long-circulating polymeric drug carriers; N; -(2-Hydroxypropyl)methacrylamide; Drug-free macromolecular therapeutics
Polymer–drug conjugates: Origins, progress to date and future directions
by Kopecek Jindřich Kopeček (pp. 49-59).
This overview focuses on bioconjugates of water-soluble polymers with low molecular weight drugs and proteins. After a short discussion of the origins of the field, the state-of-the-art is reviewed. Then research directions needed for the acceleration of the translation of nanomedicines into the clinic are outlined. Two most important directions, synthesis of backbone degradable polymer carriers and drug-free macromolecular therapeutics, a new paradigm in drug delivery, are discussed in detail. Finally, the future perspectives of the field are briefly discussed.Display Omitted
Keywords: Nanomedicine; Bioconjugates; Cancer; Degradable spacers; Long-circulating polymeric drug carriers; N; -(2-Hydroxypropyl)methacrylamide; Drug-free macromolecular therapeutics
Polymer therapeutics-prospects for 21st century: The end of the beginning
by Ruth Duncan; María J. Vicent (pp. 60-70).
The term “polymer therapeutics” was coined to describe polymeric drugs, polymer conjugates of proteins, drugs and aptamers, together with those block copolymer micelles and multicomponent non-viral vectors which contain covalent linkages. These often complex, multicomponent constructs are actually “drugs” and “macromolecular prodrugs” in contrast to drug delivery systems that simply entrap (non-covalently) therapeutic agents. They have also been described as nanomedicines. First polymer–protein conjugates entered routine clinical use in 1990 and a growing number of polymeric drugs/sequestrants and PEGylated proteins/aptamers have since come into the market. Valuable lessons have been learnt over >3 decades of clinical development, especially in relation to critical product attributes governing safety and efficacy, the validated methods needed for product characterisation. Not least there has been improved understanding of polymer therapeutic-specific biomarkers that will in future enable improved selection of patients for therapy. Advances in synthetic polymer chemistry (including control of 3D architecture), the move towards greater use of biodegradable polymers, polymers delivering combination therapy, increased understanding of polymer therapeutic critical product attributes to guide pharmaceutical development, and advances in understanding of endocytosis and intracellular trafficking pathways in health and disease are opening new opportunities for design and clinical use of polymer-based therapeutics in the decades to come.Display Omitted
Keywords: Nanomedicine; Block copolymer micelle; Dendrimer; Endocytosis; Aptamer; Polymer therapeutic biomarker
Polymer therapeutics-prospects for 21st century: The end of the beginning
by Ruth Duncan; María J. Vicent (pp. 60-70).
The term “polymer therapeutics” was coined to describe polymeric drugs, polymer conjugates of proteins, drugs and aptamers, together with those block copolymer micelles and multicomponent non-viral vectors which contain covalent linkages. These often complex, multicomponent constructs are actually “drugs” and “macromolecular prodrugs” in contrast to drug delivery systems that simply entrap (non-covalently) therapeutic agents. They have also been described as nanomedicines. First polymer–protein conjugates entered routine clinical use in 1990 and a growing number of polymeric drugs/sequestrants and PEGylated proteins/aptamers have since come into the market. Valuable lessons have been learnt over >3 decades of clinical development, especially in relation to critical product attributes governing safety and efficacy, the validated methods needed for product characterisation. Not least there has been improved understanding of polymer therapeutic-specific biomarkers that will in future enable improved selection of patients for therapy. Advances in synthetic polymer chemistry (including control of 3D architecture), the move towards greater use of biodegradable polymers, polymers delivering combination therapy, increased understanding of polymer therapeutic critical product attributes to guide pharmaceutical development, and advances in understanding of endocytosis and intracellular trafficking pathways in health and disease are opening new opportunities for design and clinical use of polymer-based therapeutics in the decades to come.Display Omitted
Keywords: Nanomedicine; Block copolymer micelle; Dendrimer; Endocytosis; Aptamer; Polymer therapeutic biomarker
The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo
by Hiroshi Maeda; Hideaki Nakamura; Jun Fang (pp. 71-79).
The EPR effect results from the extravasation of macromolecules or nanoparticles through tumor blood vessels. We here provide a historical review of the EPR effect, including its features, vascular mediators found in both cancer and inflamed tissue. In addition, architectural and physiological differences of tumor blood vessels vs that of normal tissue are commented. Furthermore, methods of augmentation of the EPR effect are described, that result in better tumor delivery and improved therapeutic effect, where nitroglycerin, angiotensin I-converting enzyme (ACE) inhibitor, or angiotensin II-induced hypertension are employed. Consequently, better therapeutic effect and reduced systemic toxicity are generally observed. Obviously, the EPR effect based delivery of nanoprobes are also useful for tumor-selective imaging agents with using fluorescent or radio nuclei in nanoprobes. We also commented a key difference between passive tumor targeting and the EPR effect in tumors, particularly as related to drug retention in tumors: passive targeting of low-molecular-weight X-ray contrast agents involves a retention period of less than a few minutes, whereas the EPR effect of nanoparticles involves a prolonged retention time—days to weeks.Color images in (A) using low molecular weight fluorescent dye [rhodamine B] is compared with that of high molecular weight in (B) using albumin conjugated with tetraetylrhodamine (67kDa), fluorescent nanoprobe. The latter (B) shows distinct fluorescent tumor image in vivo, reflecting tumor selective accumulation of nanoprobes based on the EPR. Tumor (S-180) is located at both left and right dorsal skin showing intense fluorescence. In contrast no tumor selective drug uptake is seen for the low molecular weight dye, free Rhodamine B in (A).Display Omitted
Keywords: Abbreviations; NO; nitric oxide; MMP; matrix metalloproteinase; EPR effect; enhanced permeability and retention effect; VPF; vascular permeability factor; VEGF; vascular endothelial growth factor; e-NOS; endothelial nitric oxide synthase; ACE; angiotensin converting enzyme; TNF-α; tumor necrosis factor-α; SMA; styrene-co-maleic acid; AT-II; angiotensin II; i.v.; intravenous; DTPA; diethylenetriaminepentaacetic acid; BSA; bovine serum albumin; TRITC; tetramethylrhodamine isothiocyanate; ICG; indocyanine green; HPMA; N; -(2-hydroxypropyl)methacrylamide.EPR effect mediators; Enhancement of the EPR effect; Tumor-selective drug delivery; Inflammation; Cancer; Vascular effectors; Fluorescent nanoprobes; Tumor blood vessel architecture
The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo
by Hiroshi Maeda; Hideaki Nakamura; Jun Fang (pp. 71-79).
The EPR effect results from the extravasation of macromolecules or nanoparticles through tumor blood vessels. We here provide a historical review of the EPR effect, including its features, vascular mediators found in both cancer and inflamed tissue. In addition, architectural and physiological differences of tumor blood vessels vs that of normal tissue are commented. Furthermore, methods of augmentation of the EPR effect are described, that result in better tumor delivery and improved therapeutic effect, where nitroglycerin, angiotensin I-converting enzyme (ACE) inhibitor, or angiotensin II-induced hypertension are employed. Consequently, better therapeutic effect and reduced systemic toxicity are generally observed. Obviously, the EPR effect based delivery of nanoprobes are also useful for tumor-selective imaging agents with using fluorescent or radio nuclei in nanoprobes. We also commented a key difference between passive tumor targeting and the EPR effect in tumors, particularly as related to drug retention in tumors: passive targeting of low-molecular-weight X-ray contrast agents involves a retention period of less than a few minutes, whereas the EPR effect of nanoparticles involves a prolonged retention time—days to weeks.Color images in (A) using low molecular weight fluorescent dye [rhodamine B] is compared with that of high molecular weight in (B) using albumin conjugated with tetraetylrhodamine (67kDa), fluorescent nanoprobe. The latter (B) shows distinct fluorescent tumor image in vivo, reflecting tumor selective accumulation of nanoprobes based on the EPR. Tumor (S-180) is located at both left and right dorsal skin showing intense fluorescence. In contrast no tumor selective drug uptake is seen for the low molecular weight dye, free Rhodamine B in (A).Display Omitted
Keywords: Abbreviations; NO; nitric oxide; MMP; matrix metalloproteinase; EPR effect; enhanced permeability and retention effect; VPF; vascular permeability factor; VEGF; vascular endothelial growth factor; e-NOS; endothelial nitric oxide synthase; ACE; angiotensin converting enzyme; TNF-α; tumor necrosis factor-α; SMA; styrene-co-maleic acid; AT-II; angiotensin II; i.v.; intravenous; DTPA; diethylenetriaminepentaacetic acid; BSA; bovine serum albumin; TRITC; tetramethylrhodamine isothiocyanate; ICG; indocyanine green; HPMA; N; -(2-hydroxypropyl)methacrylamide.EPR effect mediators; Enhancement of the EPR effect; Tumor-selective drug delivery; Inflammation; Cancer; Vascular effectors; Fluorescent nanoprobes; Tumor blood vessel architecture
Cancer nanomedicines: So many papers and so few drugs!
by Vincent J. Venditto; Francis C. Szoka Jr. (pp. 80-88).
This review identifies a timeline to nanomedicine anticancer drug approval using the business model of inventors, innovators and imitators. By evaluating the publication record of nanomedicine cancer therapeutics we identified a trend of very few publications prior to FDA approval. We first enumerated the publications related to cancer involving polymers, liposomes or monoclonal antibodies and determined the number of citations per publication as well as the number of published clinical trials among the publications. Combining these data with the development of specific nanomedicines, we are able to identify an invention phase consisting of seminal papers in basic science necessary for the development of a specific nanomedicine. The innovation phase includes the first report, the development and the clinical trials involving that nanomedicine. Finally, the imitation phase begins after approval when others ride the wave of success by using the same formulation for new drugs or using the same drug to validate other nanomedicines. We then focused our analysis on nanomedicines containing camptothecin derivatives, which are not yet approved including two polymers considered innovations and one liposomal formulation in the imitation phase. The conclusion that may be drawn from the analysis of the camptothecins is that approved drugs reformulated in polymeric and liposomal cancer nanomedicines have a more difficult time navigating through the approval process than the parent molecule. This is probably due to the fact that for most currently approved drugs, reformulating them in a nanocarrier provides a small increase in performance that large pharmaceutical companies do not consider being worth the time, effort and expense of development. It also appears that drug carriers have a more difficult path through the clinic than monoclonal antibodies. The added complexity of nanocarriers also deters their use to deliver new molecular entities. Thus, the new drug candidates that might be most improved by drug delivery in nanocarriers are not formulated in this fashion.Display Omitted
Keywords: Camptothecin; Liposomes; Monoclonal antibodies; Platinum therapy; Polymers
Cancer nanomedicines: So many papers and so few drugs!
by Vincent J. Venditto; Francis C. Szoka Jr. (pp. 80-88).
This review identifies a timeline to nanomedicine anticancer drug approval using the business model of inventors, innovators and imitators. By evaluating the publication record of nanomedicine cancer therapeutics we identified a trend of very few publications prior to FDA approval. We first enumerated the publications related to cancer involving polymers, liposomes or monoclonal antibodies and determined the number of citations per publication as well as the number of published clinical trials among the publications. Combining these data with the development of specific nanomedicines, we are able to identify an invention phase consisting of seminal papers in basic science necessary for the development of a specific nanomedicine. The innovation phase includes the first report, the development and the clinical trials involving that nanomedicine. Finally, the imitation phase begins after approval when others ride the wave of success by using the same formulation for new drugs or using the same drug to validate other nanomedicines. We then focused our analysis on nanomedicines containing camptothecin derivatives, which are not yet approved including two polymers considered innovations and one liposomal formulation in the imitation phase. The conclusion that may be drawn from the analysis of the camptothecins is that approved drugs reformulated in polymeric and liposomal cancer nanomedicines have a more difficult time navigating through the approval process than the parent molecule. This is probably due to the fact that for most currently approved drugs, reformulating them in a nanocarrier provides a small increase in performance that large pharmaceutical companies do not consider being worth the time, effort and expense of development. It also appears that drug carriers have a more difficult path through the clinic than monoclonal antibodies. The added complexity of nanocarriers also deters their use to deliver new molecular entities. Thus, the new drug candidates that might be most improved by drug delivery in nanocarriers are not formulated in this fashion.Display Omitted
Keywords: Camptothecin; Liposomes; Monoclonal antibodies; Platinum therapy; Polymers
Perspectives on the interface of drug delivery and tissue engineering
by Adam K. Ekenseair; F. Kurtis Kasper; Antonios G. Mikos (pp. 89-92).
Controlled drug delivery of bioactive molecules continues to be an essential component of engineering strategies for tissue defect repair. This article surveys the current challenges associated with trying to regenerate complex tissues utilizing drug delivery and gives perspectives on the development of translational tissue engineering therapies which promote spatiotemporal cell-signaling cascades to maximize the rate and quality of repair.Display Omitted
Keywords: Scaffolds; Spatiotemporal control; Extracellular matrix; Tissue regeneration; Translational medicine
Perspectives on the interface of drug delivery and tissue engineering
by Adam K. Ekenseair; F. Kurtis Kasper; Antonios G. Mikos (pp. 89-92).
Controlled drug delivery of bioactive molecules continues to be an essential component of engineering strategies for tissue defect repair. This article surveys the current challenges associated with trying to regenerate complex tissues utilizing drug delivery and gives perspectives on the development of translational tissue engineering therapies which promote spatiotemporal cell-signaling cascades to maximize the rate and quality of repair.Display Omitted
Keywords: Scaffolds; Spatiotemporal control; Extracellular matrix; Tissue regeneration; Translational medicine
Inorganic nanosystems for therapeutic delivery: Status and prospects
by Chang Soo Kim; Gülen Yesilbag Tonga; David Solfiell; Vincent M. Rotello (pp. 93-99).
Inorganic nanomaterials have an array of structural and physical properties that can be used in therapeutic delivery systems. The sizes, shapes, and surfaces of inorganic nanomaterials can be tailored to produce distinct interactions with biological systems both in vitro and in vivo. Nanoparticle cores can likewise be engineered to possess unique opticophysical properties, including upconversion, size-dependent absorbance/emission as well as magnetic properties such as superparamagnetism. These properties make inorganic nanomaterials as useful imaging agents for noninvasive diagnostics and remotely activated theragnostics. Taken together, these unique properties of inorganic nanomaterials make them promising delivery systems.Display Omitted
Keywords: Inorganic nanomaterials; Drug delivery; Upconversion; Theragnostic; Multifunctional; Imaging agent
Inorganic nanosystems for therapeutic delivery: Status and prospects
by Chang Soo Kim; Gülen Yesilbag Tonga; David Solfiell; Vincent M. Rotello (pp. 93-99).
Inorganic nanomaterials have an array of structural and physical properties that can be used in therapeutic delivery systems. The sizes, shapes, and surfaces of inorganic nanomaterials can be tailored to produce distinct interactions with biological systems both in vitro and in vivo. Nanoparticle cores can likewise be engineered to possess unique opticophysical properties, including upconversion, size-dependent absorbance/emission as well as magnetic properties such as superparamagnetism. These properties make inorganic nanomaterials as useful imaging agents for noninvasive diagnostics and remotely activated theragnostics. Taken together, these unique properties of inorganic nanomaterials make them promising delivery systems.Display Omitted
Keywords: Inorganic nanomaterials; Drug delivery; Upconversion; Theragnostic; Multifunctional; Imaging agent
Devices for overcoming biological barriers: The use of physical forces to disrupt the barriers
by Samir Mitragotri (pp. 100-103).
Overcoming biological barriers including skin, mucosal membranes, blood brain barrier as well as cell and nuclear membrane constitutes a key hurdle in the field of drug delivery. While these barriers serve the natural protective function in the body, they limit delivery of drugs into the body. A variety of methods have been developed to overcome these barriers including formulations, targeting peptides and device-based technologies. This review focuses on the use of physical methods including acoustic devices, electric devices, high-pressure devices, microneedles and optical devices for disrupting various barriers in the body including skin and other membranes. A summary of the working principles of these devices and their ability to enhance drug delivery is presented.Display Omitted
Keywords: Drug delivery; Physical; Devices; Skin; Enhancer; Non-invasive
Devices for overcoming biological barriers: The use of physical forces to disrupt the barriers
by Samir Mitragotri (pp. 100-103).
Overcoming biological barriers including skin, mucosal membranes, blood brain barrier as well as cell and nuclear membrane constitutes a key hurdle in the field of drug delivery. While these barriers serve the natural protective function in the body, they limit delivery of drugs into the body. A variety of methods have been developed to overcome these barriers including formulations, targeting peptides and device-based technologies. This review focuses on the use of physical methods including acoustic devices, electric devices, high-pressure devices, microneedles and optical devices for disrupting various barriers in the body including skin and other membranes. A summary of the working principles of these devices and their ability to enhance drug delivery is presented.Display Omitted
Keywords: Drug delivery; Physical; Devices; Skin; Enhancer; Non-invasive
Advanced materials and processing for drug delivery: The past and the future
by Ying Zhang; Hon Fai Chan; Kam W. Leong (pp. 104-120).
Design and synthesis of efficient drug delivery systems are of vital importance for medicine and healthcare. Materials innovation and nanotechnology have synergistically fueled the advancement of drug delivery. Innovation in material chemistry allows the generation of biodegradable, biocompatible, environment-responsive, and targeted delivery systems. Nanotechnology enables control over size, shape and multi-functionality of particulate drug delivery systems. In this review, we focus on the materials innovation and processing of drug delivery systems and how these advances have shaped the past and may influence the future of drug delivery.Display Omitted
Keywords: Abbreviations; CFL; continuous flow photolithography; DDS; drug delivery system; dex-HEMA; dextranhydroxyethyl methacrylate; EE; encapsulation efficiency; ELPs; elastomer-like proteins; EPR; enhanced permeability effect; GFP; green fluorescence protein; HFR; heparin–folic acid–retinoic acid; HPMA; N-(2-hydroxypropyl) methacrylamide; IPA; isopropyl alcohol; LBL; layer-by-layer; NPs; nanoparticles; O/W; oil-in-water; PAA; poly(acrylic acid); PDMS; polydimethylsiloxane; PEG; polyethylene glycol; PEG-DA; poly(ethylene glycol) diacrylate; PEG–PLA; poly(ethylene glycol)-b-polylactide; PEI; poly(ethyleneimine); PEO-PPO-PEO; poly(propylene oxide)- poly(ethylene oxide)- poly(propylene oxide); PFPE; perfluoropolyether; PGA; poly(glycol acid)/ poly (L-glutamic acid); PLA; poly(lactic acid)/polylactide; PLGA; poly (lactide-co-glycolide); PMMA; polymethyl methacrylate; pNIPAAM; poly(N-isopropylacrylamide); PRINT; particle replication in non-wetting template; PS; polystyrene; PTMC; poly(trimethylene carbonate); PVA; poly(vinyl alcohol); RAFT; reversible addition–fragmentation chain transfer; RES; reticuloendothelial system; S-FIL; step-flash imprint lithography; SDS; sodium dodecyl sulphate; SFL; stop flow lithography technique; SLP; silk-like proteins; W/O; water-in-oil; W/O/W; water-in-oil-in-waterCommercialized drug delivery system; Nanoparticle; Polyplex; Natural polymers; Polymer–drug conjugate; Combinatorial chemistry; Microfluidics; Particle replication in non-wetting template; Step-flash imprint lithography
Advanced materials and processing for drug delivery: The past and the future
by Ying Zhang; Hon Fai Chan; Kam W. Leong (pp. 104-120).
Design and synthesis of efficient drug delivery systems are of vital importance for medicine and healthcare. Materials innovation and nanotechnology have synergistically fueled the advancement of drug delivery. Innovation in material chemistry allows the generation of biodegradable, biocompatible, environment-responsive, and targeted delivery systems. Nanotechnology enables control over size, shape and multi-functionality of particulate drug delivery systems. In this review, we focus on the materials innovation and processing of drug delivery systems and how these advances have shaped the past and may influence the future of drug delivery.Display Omitted
Keywords: Abbreviations; CFL; continuous flow photolithography; DDS; drug delivery system; dex-HEMA; dextranhydroxyethyl methacrylate; EE; encapsulation efficiency; ELPs; elastomer-like proteins; EPR; enhanced permeability effect; GFP; green fluorescence protein; HFR; heparin–folic acid–retinoic acid; HPMA; N-(2-hydroxypropyl) methacrylamide; IPA; isopropyl alcohol; LBL; layer-by-layer; NPs; nanoparticles; O/W; oil-in-water; PAA; poly(acrylic acid); PDMS; polydimethylsiloxane; PEG; polyethylene glycol; PEG-DA; poly(ethylene glycol) diacrylate; PEG–PLA; poly(ethylene glycol)-b-polylactide; PEI; poly(ethyleneimine); PEO-PPO-PEO; poly(propylene oxide)- poly(ethylene oxide)- poly(propylene oxide); PFPE; perfluoropolyether; PGA; poly(glycol acid)/ poly (L-glutamic acid); PLA; poly(lactic acid)/polylactide; PLGA; poly (lactide-co-glycolide); PMMA; polymethyl methacrylate; pNIPAAM; poly(N-isopropylacrylamide); PRINT; particle replication in non-wetting template; PS; polystyrene; PTMC; poly(trimethylene carbonate); PVA; poly(vinyl alcohol); RAFT; reversible addition–fragmentation chain transfer; RES; reticuloendothelial system; S-FIL; step-flash imprint lithography; SDS; sodium dodecyl sulphate; SFL; stop flow lithography technique; SLP; silk-like proteins; W/O; water-in-oil; W/O/W; water-in-oil-in-waterCommercialized drug delivery system; Nanoparticle; Polyplex; Natural polymers; Polymer–drug conjugate; Combinatorial chemistry; Microfluidics; Particle replication in non-wetting template; Step-flash imprint lithography
Targeting receptor-mediated endocytotic pathways with nanoparticles: Rationale and advances
by Shi Xu; Bogdan Z. Olenyuk; Curtis T. Okamoto; Sarah F. Hamm-Alvarez (pp. 121-138).
Targeting of drugs and their carrier systems by using receptor-mediated endocytotic pathways was in its nascent stages 25years ago. In the intervening years, an explosion of knowledge focused on design and synthesis of nanoparticulate delivery systems as well as elucidation of the cellular complexity of what was previously-termed receptor-mediated endocytosis has now created a situation when it has become possible to design and test the feasibility of delivery of highly specific nanoparticle drug carriers to specific cells and tissue. This review outlines the mechanisms governing the major modes of receptor-mediated endocytosis used in drug delivery and highlights recent approaches using these as targets for in vivo drug delivery of nanoparticles. The review also discusses some of the inherent complexity associated with the simple shift from a ligand–drug conjugate versus a ligand–nanoparticle conjugate, in terms of ligand valency and its relationship to the mode of receptor-mediated internalization.Display Omitted
Keywords: Abbreviations; AML; acute myelogenous leukemia; AP; adaptor protein; Arf; ADP-ribosylation factor; CLIC; clathrin independent carriers; CtxB; cholera toxin B; ECM; extracellular matrix; EGF; epidermal growth factor; EGFR; epidermal growth factor receptor; EPR; enhanced permeability and retention; ER; endoplasmic reticulum; ESCRT; endosomal sorting complex required for transport; FBP; folate binding protein; FcRn; neonatal Fc receptor; FR; folate receptor; GEEC; GPI-anchored protein-enriched early endosomal compartment; GPCR; G-protein coupled receptor; GPI-AP; glycosylphosphatidyl inositol anchored protein; HFE; familial hemochromatosis protein; IGF; insulin-like growth factor; IgG; immunoglobulin G; LDL; low-density lipoprotein; LDLR; low-density lipoprotein receptor; MMP; matrix metalloproteinase; PACS1; phosphofurin acidic cluster sorting protein; pIgR; polymeric immunoglobulin receptor; Rabs; ras-like proteins from brain; SNARE; receptor for soluble N-ethylmaleimide sensitive factor attachment proteins; SPR; surface plasmon resonance; StxB; Shiga toxin B; SV40; simian virus 40; Tf; transferrin; TfR; transferrin receptor; TGF; transforming growth factor; TGN; trans-Golgi network; TTP; TfR trafficking protein; VEGFR; vascular endothelial growth factor receptorEndocytosis; Drug delivery; Cellular targeting; Multivalent targeting
Targeting receptor-mediated endocytotic pathways with nanoparticles: Rationale and advances
by Shi Xu; Bogdan Z. Olenyuk; Curtis T. Okamoto; Sarah F. Hamm-Alvarez (pp. 121-138).
Targeting of drugs and their carrier systems by using receptor-mediated endocytotic pathways was in its nascent stages 25years ago. In the intervening years, an explosion of knowledge focused on design and synthesis of nanoparticulate delivery systems as well as elucidation of the cellular complexity of what was previously-termed receptor-mediated endocytosis has now created a situation when it has become possible to design and test the feasibility of delivery of highly specific nanoparticle drug carriers to specific cells and tissue. This review outlines the mechanisms governing the major modes of receptor-mediated endocytosis used in drug delivery and highlights recent approaches using these as targets for in vivo drug delivery of nanoparticles. The review also discusses some of the inherent complexity associated with the simple shift from a ligand–drug conjugate versus a ligand–nanoparticle conjugate, in terms of ligand valency and its relationship to the mode of receptor-mediated internalization.Display Omitted
Keywords: Abbreviations; AML; acute myelogenous leukemia; AP; adaptor protein; Arf; ADP-ribosylation factor; CLIC; clathrin independent carriers; CtxB; cholera toxin B; ECM; extracellular matrix; EGF; epidermal growth factor; EGFR; epidermal growth factor receptor; EPR; enhanced permeability and retention; ER; endoplasmic reticulum; ESCRT; endosomal sorting complex required for transport; FBP; folate binding protein; FcRn; neonatal Fc receptor; FR; folate receptor; GEEC; GPI-anchored protein-enriched early endosomal compartment; GPCR; G-protein coupled receptor; GPI-AP; glycosylphosphatidyl inositol anchored protein; HFE; familial hemochromatosis protein; IGF; insulin-like growth factor; IgG; immunoglobulin G; LDL; low-density lipoprotein; LDLR; low-density lipoprotein receptor; MMP; matrix metalloproteinase; PACS1; phosphofurin acidic cluster sorting protein; pIgR; polymeric immunoglobulin receptor; Rabs; ras-like proteins from brain; SNARE; receptor for soluble N-ethylmaleimide sensitive factor attachment proteins; SPR; surface plasmon resonance; StxB; Shiga toxin B; SV40; simian virus 40; Tf; transferrin; TfR; transferrin receptor; TGF; transforming growth factor; TGN; trans-Golgi network; TTP; TfR trafficking protein; VEGFR; vascular endothelial growth factor receptorEndocytosis; Drug delivery; Cellular targeting; Multivalent targeting
Pharmacokinetic considerations for targeted drug delivery
by Fumiyoshi Yamashita; Mitsuru Hashida (pp. 139-147).
Drug delivery systems involve technology designed to maximize therapeutic efficacy of drugs by controlling their biodistribution profile. In order to optimize a function of the delivery systems, their biodistribution characteristics should be systematically understood. Pharmacokinetic analysis based on the clearance concepts provides quantitative information of the biodistribution, which can be related to physicochemical properties of the delivery system. Various delivery systems including macromolecular drug conjugates, chemically or genetically modified proteins, and particulate drug carriers have been designed and developed so far. In this article, we review physiological and pharmacokinetic implications of the delivery systems.Display Omitted
Keywords: Drug delivery system; Targeted drug delivery; Pharmacokinetics; Tissue uptake clearance; Macromolecular prodrugs; Chemical modified proteins; Nanoparticles; Liposomes
Pharmacokinetic considerations for targeted drug delivery
by Fumiyoshi Yamashita; Mitsuru Hashida (pp. 139-147).
Drug delivery systems involve technology designed to maximize therapeutic efficacy of drugs by controlling their biodistribution profile. In order to optimize a function of the delivery systems, their biodistribution characteristics should be systematically understood. Pharmacokinetic analysis based on the clearance concepts provides quantitative information of the biodistribution, which can be related to physicochemical properties of the delivery system. Various delivery systems including macromolecular drug conjugates, chemically or genetically modified proteins, and particulate drug carriers have been designed and developed so far. In this article, we review physiological and pharmacokinetic implications of the delivery systems.Display Omitted
Keywords: Drug delivery system; Targeted drug delivery; Pharmacokinetics; Tissue uptake clearance; Macromolecular prodrugs; Chemical modified proteins; Nanoparticles; Liposomes
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