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Nanotechnology applied to the treatment of malaria.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Despite the fact that we live in an era of advanced technology and innovation, infectious diseases, like malaria, continue to be one the greatest health challenges worldwide. The main drawbacks of conventional malaria chemotherapy are the development of multiple drug resistance and the non-specific targeting to intracellular parasites, resulting in high dose requirements and subsequent intolerable toxicity. Nanosized carriers have been receiving special attention with the aim of minimizing the side effects of drug therapy, such as poor bioavailability and the selectivity of drugs. Several nanosized delivery systems hav...
Source: Advanced Drug Delivery Reviews - November 12, 2009 Category: Drugs & Pharmacology Authors: Santos-Magalhães NS, Mosqueira VC Tags: Adv Drug Deliv Rev Source Type: journals

Nanotechnology-based systems for the treatment and prevention of HIV/AIDS.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The HIV/AIDS pandemic is an increasing global burden with devastating health-related and socioeconomic effects. The widespread use of antiretroviral therapy has dramatically improved life quality and expectancy of infected individuals, but limitations of currently available drug regimens and dosage forms, alongside with the extraordinary adapting capacity of the virus, have impaired further success. Alongside, circumventing the escalating number of new infections can only be attained with effective and practical preventative strategies. Recent advances in the field of drug delivery are providing evidence that engineere...
Source: Advanced Drug Delivery Reviews - November 12, 2009 Category: Drugs & Pharmacology Authors: das Neves J, Amiji MM, Bahia MF, Sarmento B Tags: Adv Drug Deliv Rev Source Type: journals

New old challenges in tuberculosis: Potentially effective nanotechnologies in drug delivery.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Tuberculosis (TB) is the second most deadly infectious disease. Despite potentially curative pharmacotherapies being available for over fifty years, the length of the treatment and the pill burden can hamper patient lifestyle. Thus, low compliance and adherence to administration schedules remain the main reasons for therapeutic failure and contribute to the development of multidrug-resistant (MDR) strains. Pediatric patients constitute a high risk population. Most of the first-line drugs are not commercially available in pediatric form. The design of novel antibiotics attempts to overcome drug resistance, to shorten th...
Source: Advanced Drug Delivery Reviews - November 12, 2009 Category: Drugs & Pharmacology Authors: Sosnik A, Carcaboso AM, Glisoni RJ, Moretton MA, Chiappetta DA Tags: Adv Drug Deliv Rev Source Type: journals

Emerging nanotechnology-based strategies for the identification of microbial pathogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Infectious diseases are still a major healthcare problem. From food intoxication and contaminated water, to hospital-acquired diseases and pandemics, infectious agents cause disease throughout the world. Despite advancements in pathogens' identification, some of the gold-standard diagnostic methods have limitations, including laborious sample preparation, bulky instrumentation and slow data readout. In addition, new field-deployable diagnostic modalities are urgently needed in first responder and point of care applications. Apart from compact, these sensors must be sensitive, specific, robust and fast, in order to faci...
Source: Advanced Drug Delivery Reviews - November 12, 2009 Category: Drugs & Pharmacology Authors: Kaittanis C, Santra S, Perez JM Tags: Adv Drug Deliv Rev Source Type: journals

Fabrication of Gold Nanoparticles for targeted therapy in pancreatic cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The targeted delivery of a drug should result in enhanced therapeutic efficacy with low to minimal side effects. This is a widely accepted concept, but limited in application due to lack of available technologies and process of validation. Biomedical nanotechnology can play an important role in this respect. Biomedical nanotechnology is a burgeoning field with myriads of opportunities and possibilities for advancing medical science and disease treatment. Cancer nanotechnology (1-100nm size range) is expected to change the very foundations of cancer treatment, diagnosis and detection. Nanomaterials, especially gold nano...
Source: Advanced Drug Delivery Reviews - November 12, 2009 Category: Drugs & Pharmacology Authors: Patra CR, Bhattacharya R, Mukhopadhyay D, Mukherjee P Tags: Adv Drug Deliv Rev Source Type: journals

Immunogenicity and immunomodulatory properties of HPMA-based polymers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
HPMA copolymers are one of the most promising drug carriers as their biophysical and biochemical properties, including their immunocompatibility, are very favorable. So far, there is no evidence that HPMA copolymers can interact with the immune system in a way that would lead either to suppression of some of its crucial functions or to inappropriate activation with possible serious side-effects and thus we can conclude that HPMA copolymers are convincingly proved to be "immunologically" safe. Moreover, it was shown both in mice and humans that HPMA copolymer-bound doxorubicin (DOX-HPMA) conjugates possess beside powerf...
Source: Advanced Drug Delivery Reviews - November 12, 2009 Category: Drugs & Pharmacology Authors: Ríhová B, Kovář M Tags: Adv Drug Deliv Rev Source Type: journals

Nanotechnology applications for improved delivery of antiretroviral drugs to the brain.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Human immunodeficiency virus (HIV) can gain access to the central nervous system during the early course of primary infection. Once in the brain compartment the virus actively replicates to form an independent viral reservoir, resulting in debilitating neurological complications, latent infection and drug resistance. Current antiretroviral drugs (ARVs) often fail to effectively reduce the HIV viral load in the brain. This, in part, is due to the poor transport of many ARVs, in particular protease inhibitors, across the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSBF). Studies have shown that nano...
Source: Advanced Drug Delivery Reviews - November 12, 2009 Category: Drugs & Pharmacology Authors: Wong HL, Chattopadhyay N, Wu XY, Bendayan R Tags: Adv Drug Deliv Rev Source Type: journals

Non-polymeric nano-carriers in HIV/AIDS drug delivery and targeting.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Development of an effective drug delivery approach for the treatment of HIV/AIDS is a global challenge. The conventional drug delivery approaches including Highly Active Anti Retroviral Therapy (HAART) have increased the life span of the HIV/AIDS patient. However, the eradication of HIV is still not possible with these approaches due to some limitations. Emergence of polymeric and non-polymeric nanotechnological approaches can be opportunistic in this direction. Polymeric carriers like, dendrimers and nanoparticles have been reported for the targeting of anti HIV drugs. The synthetic pathways as well polymeric framewor...
Source: Advanced Drug Delivery Reviews - November 11, 2009 Category: Drugs & Pharmacology Authors: Gupta U, Jain NK Tags: Adv Drug Deliv Rev Source Type: journals

Nanotechnology Solutions for Infectious Diseases in Developing Nations.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19913580 [PubMed - as supplied by publisher] (Source: Advanced Drug Delivery Reviews)
Source: Advanced Drug Delivery Reviews - November 11, 2009 Category: Drugs & Pharmacology Authors: Sosnik A, Amiji M Tags: Adv Drug Deliv Rev Source Type: journals

Nanoparticles for Detection and Diagnosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Nanoparticle-based platforms for identification of chemical and biological agents offer substantial benefits to biomedical and environmental science. These platforms benefit from the availability of a wide variety of core materials as well as the unique physical and chemical properties of these nanoscale materials. This review surveys some of the emerging approaches in the field of nanoparticle based detection systems, highlighting the nanoparticle based screening methods for metal ions, proteins, nucleic acids, and biologically relevant small molecules. PMID: 19913581 [PubMed - as supplied by publisher] (Source: A...
Source: Advanced Drug Delivery Reviews - November 11, 2009 Category: Drugs & Pharmacology Authors: Agasti SS, Rana S, Park MH, Kim CK, You CC, Rotello VM Tags: Adv Drug Deliv Rev Source Type: journals

Beyond oncology - application of HPMA copolymers in non-cancerous diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Macromolecular drug conjugates have been developed to improve the efficacy and safety profile of various therapeutic agents for many years. Among them, N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-drug conjugates are the most extensively studied delivery platforms for the effective treatment of cancer. In recent years, the applications of HPMA copolymers for the treatment of a broader range of non-cancerous diseases have also been explored. This review highlights the recent developments in the rational design, synthesis, and evaluation of novel HPMA copolymer-drug conjugates for non-cancerous diseases, such as m...
Source: Advanced Drug Delivery Reviews - November 9, 2009 Category: Drugs & Pharmacology Authors: Liu XM, Miller SC, Wang D Tags: Adv Drug Deliv Rev Source Type: journals

Targeted hyperthermia using metal nanoparticles.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19909777 [PubMed - as supplied by publisher] (Source: Advanced Drug Delivery Reviews)
Source: Advanced Drug Delivery Reviews - November 9, 2009 Category: Drugs & Pharmacology Authors: Cherukuri P, Glazer ES, Curley SA Tags: Adv Drug Deliv Rev Source Type: journals

Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Magnetic nanoparticles (MNPs) represent a class of non-invasive imaging agents that have been developed for magnetic resonance (MR) imaging. These MNPs have traditionally been used for disease imaging via passive targeting, but recent advances have opened the door to cellular-specific targeting, drug delivery, and multi-modal imaging by these nanoparticles. As more elaborate MNPs are envisioned, adherence to proper design criteria (e.g. size, coating, molecular functionalization) becomes even more essential. This review summarizes the design parameters that affect MNP performance in vivo, including the physicochemical ...
Source: Advanced Drug Delivery Reviews - November 9, 2009 Category: Drugs & Pharmacology Authors: Veiseh O, Gunn J, Zhang M Tags: Adv Drug Deliv Rev Source Type: journals

Modified natural nanoparticles as contrast agents for medical imaging.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The development of novel and effective contrast agents is one of the drivers of the ongoing improvement in medical imaging. Many of the new agents reported are nanoparticle-based. There are a variety of natural nanoparticles known, e.g. lipoproteins, viruses or ferritin. Natural nanoparticles have advantages as delivery platforms such as biodegradability. In addition, our understanding of natural nanoparticles is quite advanced, allowing their adaptation as contrast agents. They can be labeled with small molecules or ions such as Gd(3+) to act as contrast agents for magnetic resonance imaging, (18)F to act as positron ...
Source: Advanced Drug Delivery Reviews - November 6, 2009 Category: Drugs & Pharmacology Authors: Cormode DP, Jarzyna PA, Mulder WJ, Fayad ZA Tags: Adv Drug Deliv Rev Source Type: journals

Better safe than sorry: Understanding the toxicological properties of inorganic nanoparticles manufactured for biomedical applications.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The development of nanoparticles for biomedical applications including medical imaging and drug delivery is currently undergoing a dramatic expansion. However, as the range of nanoparticle types and applications increases, it is also clear that the potential toxicities of these novel materials and the properties driving such toxic responses must also be understood. Indeed, a detailed assessment of the factors that influence the biocompatibility and/or toxicity of nanoparticles is crucial for the safe and sustainable development of the emerging nanotechnologies. This review summarizes some of the recent developments in ...
Source: Advanced Drug Delivery Reviews - November 6, 2009 Category: Drugs & Pharmacology Authors: Fadeel B, Garcia-Bennett AE Tags: Adv Drug Deliv Rev Source Type: journals

Targeted delivery using inorganic nanosystem.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19900498 [PubMed - as supplied by publisher] (Source: Advanced Drug Delivery Reviews)
Source: Advanced Drug Delivery Reviews - November 6, 2009 Category: Drugs & Pharmacology Authors: Mukherjee P Tags: Adv Drug Deliv Rev Source Type: journals

Targeted delivery of low molecular drugs using chitosan and its derivatives.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Chitosan has prompted the continuous impetus for the development of safe and effective drug delivery systems because of its unique physicochemical and biological characteristics. The primary hydroxyl and amine groups located on the backbone of chitosan allow for chemical modification to control its physical properties. When the hydrophobic moiety is conjugated to a chitosan molecule, the resulting amphiphile may form self-assembled nanoparticles that can encapsulate a quantity of drugs and deliver them to a specific site of action. Chemical attachment of the drug to the chitosan throughout the functional linker may pro...
Source: Advanced Drug Delivery Reviews - October 26, 2009 Category: Drugs & Pharmacology Authors: Park JH, Saravanakumar G, Kim K, Kwon IC Tags: Adv Drug Deliv Rev Source Type: journals

Chitosan-based systems for molecular imaging.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Molecular imaging enables the non-invasive assessment of biological and biochemical processes in living subjects. Such technologies therefore have the potential to enhance our understanding of disease and drug activity during preclinical and clinical drug development. Molecular imaging allows a repetitive and non-invasive study of the same living subject using identical or alternative biological imaging assays at different time points, thus harnessing the statistical power of longitudinal studies, and reducing the number of animals required and cost. Chitosan is a hydrophilic and non-antigenic biopolymer and has a low ...
Source: Advanced Drug Delivery Reviews - October 24, 2009 Category: Drugs & Pharmacology Authors: Agrawal P, Strijkers GJ, Nicolay K Tags: Adv Drug Deliv Rev Source Type: journals

Preface Mitochondrial Medicine and Therapeutics, Part II.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19835920 [PubMed - as supplied by publisher] (Source: Advanced Drug Delivery Reviews)
Source: Advanced Drug Delivery Reviews - October 12, 2009 Category: Drugs & Pharmacology Authors: Hamm-Alvarez S, Cadenas E Tags: Adv Drug Deliv Rev Source Type: journals

Advanced drug delivery in the post-genomic era.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19819276 [PubMed - as supplied by publisher] (Source: Advanced Drug Delivery Reviews)
Source: Advanced Drug Delivery Reviews - October 7, 2009 Category: Drugs & Pharmacology Authors: Lee VH Tags: Adv Drug Deliv Rev Source Type: journals

Squalene: A natural triterpene for use in disease management and therapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Squalene is a natural lipid belonging to the terpenoid family and a precursor of cholesterol biosynthesis. It is synthesized in humans and also in a wide array of organisms and substances, from sharks to olives and even bran, among others. Because of its significant dietary benefits, biocompatibility, inertness, and other advantageous properties, squalene is extensively used as an excipient in pharmaceutical formulations for disease management and therapy. In addition, squalene acts as a protective agent and has been shown to decrease chemotherapy-induced side-effects. Moreover, squalene alone exhibits chemopreventive ...
Source: Advanced Drug Delivery Reviews - October 1, 2009 Category: Drugs & Pharmacology Authors: Reddy LH, Couvreur P Tags: Adv Drug Deliv Rev Source Type: journals

Safety and efficacy of sodium caprate in promoting oral drug absorption: From in vitro to the clinic.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A major challenge in oral drug delivery is the development of novel dosage forms to promote absorption of poorly permeable drugs across the intestinal epithelium. To date, no absorption promoter has been approved in a formulation specifically designed for oral delivery of Class III molecules. Promoters that are designated safe for human consumption have been licensed for use in a recently approved buccal insulin spray delivery system and also for many years as part of an ampicillin rectal suppository. Unlike buccal and rectal delivery, oral formulations containing absorption promoters have the additional technical hurd...
Source: Advanced Drug Delivery Reviews - September 29, 2009 Category: Drugs & Pharmacology Authors: Maher S, Leonard TW, Jacobsen J, Brayden DJ Tags: Adv Drug Deliv Rev Source Type: journals

Biodegradation, biodistribution and toxicity of chitosan.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Chitosan is a natural polysaccharide that has attracted significant scientific interest during the last two decades. It is a potentially biologically compatible material that is chemically versatile (-NH(2) groups and various M(w)). These two basic properties have been used by drug delivery and tissue engineering scientists to create a plethora of formulations and scaffolds that show promise in healthcare. Despite the high number of published studies, chitosan is not approved by the FDA for any product in drug delivery, and as a consequence very few biotech companies are using this material. This review will aim to pro...
Source: Advanced Drug Delivery Reviews - September 29, 2009 Category: Drugs & Pharmacology Authors: Kean T, Thanou M Tags: Adv Drug Deliv Rev Source Type: journals

Chitosan-based hydrogels for controlled, localized drug delivery.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hydrogels are high-water content materials prepared from cross-linked polymers that are able to provide sustained, local delivery of a variety of therapeutic agents. Use of the natural polymer, chitosan, as the scaffold material in hydrogels has been highly pursued thanks to the polymer's biocompatibility, low toxicity, and biodegradability. The advanced development of chitosan hydrogels has led to new drug delivery systems that release their payloads under varying environmental stimuli. In addition, thermosensitive hydrogel variants have been developed to form a chitosan hydrogel in situ, precluding the need for surgi...
Source: Advanced Drug Delivery Reviews - September 28, 2009 Category: Drugs & Pharmacology Authors: Bhattarai N, Gunn J, Zhang M Tags: Adv Drug Deliv Rev Source Type: journals

Chitosan-based formulations for delivery of DNA and siRNA.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Among non-viral vectors, chitosan and chitosan derivatives have been developed in vitro and in vivo for DNA and siRNA delivery systems because of their cationic charge, biodegradability and biocompatibility, as well as their mucoadhesive and permeability-enhancing properties. However, the transfection efficiency of chitosan is too low for clinical application. Studies indicated that the transfection efficiency depends on a series of chitosan-based formulation parameters, such as the Mw of chitosan, its degree of deacetylation, the charge ratio of chitosan to DNA/siRNA (N/P ratio), the chitosan salt form used, the DNA/s...
Source: Advanced Drug Delivery Reviews - September 27, 2009 Category: Drugs & Pharmacology Authors: Mao S, Sun W, Kissel T Tags: Adv Drug Deliv Rev Source Type: journals

Molecular and magnetic resonance imaging: The value of immunoliposomes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Molecular imaging has the potential to transform the field of diagnostic imaging through enabling far more detailed investigation and characterisation of disease processes than is currently possible. Magnetic resonance imaging (MRI) is capable of three-dimensional non-invasive imaging of opaque tissues at near cellular resolution. Among the imaging techniques available today, MRI has, perhaps, the greatest potential to exploit the possibilities that molecular imaging presents. Nanoparticles are the focus of intense research, due to a wide variety of potential applications in the biomedical, optical, and electronic fiel...
Source: Advanced Drug Delivery Reviews - September 27, 2009 Category: Drugs & Pharmacology Authors: Kozlowska D, Foran P, Macmahon P, Shelly MJ, Eustace S, O'Kennedy R Tags: Adv Drug Deliv Rev Source Type: journals

Micro- and nanotechnologies for intelligent and responsive biomaterial-based medical systems.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Advances in medical treatments of a wide variety of pathophysiological conditions require the development of better therapeutic agents, as well as a combination of the required therapeutic agents with device-integrated biomaterials that can serve as sensors and carriers. Combination of micro- and nanofabricated systems with intelligent biomaterials that have the ability to sense and respond is a promising avenue for the development of better diagnostic and therapeutic medical systems. Micro- and nano-electromechanical systems (MEMs and NEMs) are now becoming a family of potentially powerful new technologies for drug de...
Source: Advanced Drug Delivery Reviews - September 12, 2009 Category: Drugs & Pharmacology Authors: Caldorera-Moore M, Peppas NA Tags: Adv Drug Deliv Rev Source Type: journals

Strategies for reducing oxidative damage in ageing skeletal muscle.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It is recognised that reactive oxygen species (ROS) are both key regulators of cellular signalling and initiators of oxidative damage to DNA, lipids and proteins under different circumstances. Thus in skeletal muscle from animals and humans, studies indicate that ROS can potentially contribute to the pathophysiologogy of the age-related loss of skeletal muscle mass and function, while additionally acting as a key signal for contraction-induced adaptations in the tissue. The specific nature and sources of generation of the ROS contributing to these actions remain unknown, but the combination of physiological and patholo...
Source: Advanced Drug Delivery Reviews - September 4, 2009 Category: Drugs & Pharmacology Authors: Jackson MJ Tags: Adv Drug Deliv Rev Source Type: journals

Optimizing the future for biotechnology therapies, the key role of protein engineering.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19735684 [PubMed - as supplied by publisher] (Source: Advanced Drug Delivery Reviews)
Source: Advanced Drug Delivery Reviews - September 3, 2009 Category: Drugs & Pharmacology Authors: Camarero JA Tags: Adv Drug Deliv Rev Source Type: journals

Mitochondrial kinases in cell signaling: facts and perspectives.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Phylogenetic studies had shown that evolution of mitochondria occurred in parallel with the maturation of kinases implicated in growth and final size of modern organisms. In the last years, different reports confirmed that MAPKs, Akt, PKA and PKC are present in mitochondria, particularly in the intermembrane space and inner membrane where they meet mitochondrial constitutive upstream activators. Although a priori phosphorylation is the apparent aim of translocation, new perspectives indicate that kinase activation depends on redox status as determined by the mitochondrial production of oxygen species. We observed that ...
Source: Advanced Drug Delivery Reviews - September 2, 2009 Category: Drugs & Pharmacology Authors: Antico Arciuch VG, Alippe Y, Carreras MC, Poderoso JJ Tags: Adv Drug Deliv Rev Source Type: journals

Mitochondrial biogenesis in exercise and in ageing.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mitochondrial biogenesis is critical for the normal function of cells. It is well known that mitochondria are produced and eventually after normal functioning they are degraded. Thus, the actual level of mitochondria in cells is dependent both on the synthesis and the degradation. Ever since the proposal of the mitochondrial theory of ageing by Jaime Miquel in the 70's, it was appreciated that mitochondria, which are both a target and a source of radicals in cells, are most important organelles to understand ageing. Thus, a common feature between cell physiology of ageing and exercise is that in both situations mitocho...
Source: Advanced Drug Delivery Reviews - August 27, 2009 Category: Drugs & Pharmacology Authors: Viña J, Gomez-Cabrera MC, Borras C, Froio T, Sanchis-Gomar F, Martinez-Bello VE, Pallardo FV Tags: Adv Drug Deliv Rev Source Type: journals

Mitochondrial targeting of electron scavenging antioxidants: Regulation of selective oxidation vs random chain reactions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Effective regulation of highly compartmentalized production of reactive oxygen species and peroxidation reactions in mitochondria requires targeting of small molecule antioxidants and antioxidant enzymes into the organelles. This review describes recently developed approaches to mitochondrial targeting of small biologically active molecules based on: (i) preferential accumulation in mitochondria because of their hydrophobicity and positive charge (hydrophobic cations), (ii) binding with high affinity to an intra-mitochondrial constituent, and (iii) metabolic conversions by specific mitochondrial enzymes to reveal an ac...
Source: Advanced Drug Delivery Reviews - August 27, 2009 Category: Drugs & Pharmacology Authors: Kagan VE, Wipf P, Stoyanovsky D, Greenberger JS, Borisenko G, Belikova NA, Yanamala N, Samhan Arias AK, Tungekar MA, Jiang J, Tyurina YY, Ji J, Klein-Seetharaman J, Pitt BR, Shvedovah AA, Bayır H Tags: Adv Drug Deliv Rev Source Type: journals

PI-3-K and AKT: Onto the mitochondria.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The role of PI-3-K in regulation of mitochondrial functions is becoming a field that draws attentions from cancer as well as metabolic diseases. In this review, we focus on the action of the major downstream target of PI-3-K, the serine/threonine kinase AKT, a proto-oncoprotein. We reviewed the functions of AKT in the mitochondrial intrinsic apoptosis pathway. We analyzed how AKT regulates the different factors in the Bcl-2 family of anti- and pro-apoptotic factors either directly or indirectly. We further reviewed the role of AKT in regulating mitochondrial coupled glycolysis through hexokinase II and VDAC. This revie...
Source: Advanced Drug Delivery Reviews - August 27, 2009 Category: Drugs & Pharmacology Authors: Stiles BL Tags: Adv Drug Deliv Rev Source Type: journals

Mitochondria in the elderly: is acetylcarnitine a rejuvenator?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Endogenous acetylcarnitine is an indicator of acetyl-CoA synthesized by multiple metabolic pathways involving carbohydrates, amino acids, fatty acids, sterols, and ketone bodies, and utilized mainly by the tricarboxylic acid cycle. Acetylcarnitine supplementation has beneficial effects in elderly animals and humans, including restoration of mitochondrial content and function. These effects appear to be dose-dependent and occur even after short-term therapy. In order to set the stage for understanding the mechanism of action of acetylcarnitine, we review the metabolism and role of this compound. We suggest that acetylat...
Source: Advanced Drug Delivery Reviews - August 27, 2009 Category: Drugs & Pharmacology Authors: Rosca MG, Lemieux H, Hoppel CL Tags: Adv Drug Deliv Rev Source Type: journals

The energy-redox axis in aging and age-related neurodegeneration.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Decrease in mitochondrial energy-transducing capacity is a feature of the aging process that accompanies redox alterations, such as increased generation of mitochondrial oxidants, altered GSH status, and increased protein oxidation. The decrease in mitochondrial energy-transducing capacity and altered redox status should be viewed as a concerted process that embodies the mitochondrial energy - redox axis and is linked through various mechanisms including: (a) an inter-convertible reducing equivalents pool (i.e., NAD(P)(+)/NAD(P)H) and (b) redox-mediated protein post-translational modifications involved in energy metabo...
Source: Advanced Drug Delivery Reviews - August 25, 2009 Category: Drugs & Pharmacology Authors: Yap LP, Garcia JV, Han D, Cadenas E Tags: Adv Drug Deliv Rev Source Type: journals

Regulated Production of Free Radicals by the Mitochondrial Electron Transport Chain: Cardiac Ischemic Preconditioning.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Excessive production of free radicals by mitochondria is associated with, and likely contributes to, the progression of numerous pathological conditions. Nevertheless, the production of free radicals by the mitochondria may have important biological functions under normal or stressed conditions by activating or modulating redox-sensitive cellular signaling pathways. This raises the intriguing possibility that regulated mitochondrial free radical production occurs via mechanisms that are distinct from pathologies associated with oxidative damage. Indeed, the capacity of mitochondria to produce free radicals in a limited...
Source: Advanced Drug Delivery Reviews - August 25, 2009 Category: Drugs & Pharmacology Authors: Matsuzaki S, Szweda PA, Szweda LI, Humphries KM Tags: Adv Drug Deliv Rev Source Type: journals

Mitochondria and reactive oxygen and nitrogen species in neurological disorders and stroke: Therapeutic implications.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mitochondria represent both the main source and target of reactive oxygen and nitrogen species (RONS). In view of the large energy expenditure made by neurons during neurotransmission, an intact mitochondrial function is of paramount importance for the correct function of the brain. Accordingly, the search of therapeutic strategies against situations in which there is an abnormal brain function, such neurological disorders and stroke, should be focused towards mitochondria. Here, we have reviewed the normal and abnormal mitochondrial bioenergetics and dynamics, highlighting the relevance that, for these processes in th...
Source: Advanced Drug Delivery Reviews - August 25, 2009 Category: Drugs & Pharmacology Authors: Bolaños JP, Moro MA, Lizasoain I, Almeida A Tags: Adv Drug Deliv Rev Source Type: journals

Carnitine, mitochondrial function and therapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19716391 [PubMed - as supplied by publisher] (Source: Advanced Drug Delivery Reviews)
Source: Advanced Drug Delivery Reviews - August 25, 2009 Category: Drugs & Pharmacology Authors: Zammit VA, Ramsay RR, Bonomini M, Arduini A Tags: Adv Drug Deliv Rev Source Type: journals

Targeting mitochondrial biogenesis for preventing and treating insulin resistance in diabetes and obesity: Hope from natural mitochondrial nutrients.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Insulin resistance is an important feature of type 2 diabetes and obesity. The underlying mechanisms of insulin resistance are still unclear and may involve pathological changes in multiple tissues. Mitochondrial dysfunction, including mitochondrial loss and over-production of oxidants, has been suggested to be involved in the development of insulin resistance. Increasing evidence suggests that targeting mitochondria to protect mitochondria function as a unique measure, i.e., mitochondrial medicine, could prevent and ameliorate various diseases associated with mitochondrial dysfunction. In this review, we have summariz...
Source: Advanced Drug Delivery Reviews - August 25, 2009 Category: Drugs & Pharmacology Authors: Liu J, Shen W, Zhao B, Wang Y, Wertz K, Weber P, Zhang P Tags: Adv Drug Deliv Rev Source Type: journals

Opportunities in discovery and delivery of anticancer drugs targeting mitochondria and cancer cell metabolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cancer cells are characterized by self-sufficiency in the absence of growth signals, their ability to evade apoptosis, resistance to anti-growth signals, sustained angiogenesis, uncontrolled proliferation, and invasion and metastasis. Alterations in cellular bioenergetics are an emerging hallmark of cancer. The mitochondrion is the major organelle implicated in the cellular bioenergetic and biosynthetic changes accompanying cancer. These bioenergetic modifications contribute to the invasive, metastatic and adaptive properties typical in most tumors. Moreover, mitochondrial DNA mutations complement the bioenergetic chan...
Source: Advanced Drug Delivery Reviews - August 25, 2009 Category: Drugs & Pharmacology Authors: Pathania D, Millard M, Neamati N Tags: Adv Drug Deliv Rev Source Type: journals

The Failure of Mitochondria Leads to Neurodegeneration: Do Mitochondria Need A Jump Start?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mitochondria are the power engine generating biochemical energy in the cell. Mitochondrial dysfunction and bioenergy deficiency is closely linked to the pathogenesis of neurodegenerative disorders. Mitochondria play a variety of roles by integrating extracellular signals and executing important intracellular events in neuronal survival and death. In this context, the regulation of mitochondrial function via therapeutic approaches may exert some salutary and neuroprotective mechanisms. Understanding the relationship of mitochondria-dependent pathogenesis may provide important pharmacological utility in the treatment of ...
Source: Advanced Drug Delivery Reviews - August 25, 2009 Category: Drugs & Pharmacology Authors: Lee J, Boo JH, Ryu H Tags: Adv Drug Deliv Rev Source Type: journals

Combination therapy: Opportunities and challenges for polymer-drug conjugates as anticancer nanomedicines.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The discovery of new molecular targets and the subsequent development of novel anticancer agents is opening new possibilities for drug combination therapy as anticancer treatment. Polymer-drug conjugates are well established for the delivery of a single therapeutic agent, but only in very recent years their use has been extended to the delivery of multi-agent therapy. These early studies revealed the therapeutic potential of this application but raised new challenges (namely, drug loading and drugs ratio, characterisation, development of suitable carriers) that need to be addressed for a successful optimisation of the ...
Source: Advanced Drug Delivery Reviews - August 18, 2009 Category: Drugs & Pharmacology Authors: Greco F, Vicent MJ Tags: Adv Drug Deliv Rev Source Type: journals

Design and development of polymer conjugates as anti-angiogenic agents.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is one of the central key points in tumor progression and metastasis. Consequently, it became an important target in cancer therapy, making novel angiogenesis inhibitors a new modality of anticancer agents. Although relative to conventional chemotherapy, anti-angiogenic agents display a safer toxicity profile, the vast majority of these agents are low-molecular-weight compounds exhibiting poor pharmacokinetic profile with short half-life in the bloodstream and high overall clearance rate. The "Polymer Therapeutics" field has significantly i...
Source: Advanced Drug Delivery Reviews - August 18, 2009 Category: Drugs & Pharmacology Authors: Segal E, Satchi-Fainaro R Tags: Adv Drug Deliv Rev Source Type: journals

Development of HPMA copolymer anticancer conjugates: Clinical experience and lessons learnt.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The concept of polymer-drug conjugates was proposed more than 30years ago, and an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugate of doxorubicin covalently bound to the polymer backbone by a Gly-Phe-Leu-Gly peptidyl linker (FCE28068) became the first synthetic polymer-based anticancer conjugate to enter clinical trial in 1994. This conjugate arose from rational design attempting to capitalise on passive tumour targeting by the enhanced permeability and retention effect and, at the cellular level, lysosomotropic drug delivery to improve therapeutic index. Early clinical results were promising, confirming ac...
Source: Advanced Drug Delivery Reviews - August 18, 2009 Category: Drugs & Pharmacology Authors: Duncan R Tags: Adv Drug Deliv Rev Source Type: journals

Clinical experience with anthracycline antibiotics-HPMA copolymer-human immunoglobulin conjugates.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This paper reviews an early clinical experience with anthracycline (epirubicin; Epi or doxorubicin; Dox) containing N-(2-hydroyxypropyl)methacrylamide copolymer carrier targeted with autologous or commercial human immunoglobulin in six patients aged 28 - 55 suffering from therapy-resistant metastatic cancer. More than 100 biochemical, hematological and immunological parameters including nine tumor markers, were tested in blood samples taken 24 h after the first and up to 10 months after the last application. The intravenous application proceeded without serious adverse or side effects and did not require hospitalizatio...
Source: Advanced Drug Delivery Reviews - August 10, 2009 Category: Drugs & Pharmacology Authors: Rihova B Tags: Adv Drug Deliv Rev Source Type: journals

Polymeric carriers: Preclinical safety and the regulatory implications for design and development of polymer therapeutics.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Since the early 1990s polymer-protein conjugates (included PEGylated enzymes and cytokines), polymeric drugs and polymeric sequestrants have been entering the market as innovative polymer-based therapeutics. Initially these products were most frequently developed as novel anticancer agents; indeed they can be considered first generation "nanomedicines". More recently, a much broader range of life-threatening and debilitating diseases (e.g. viral infections, arthritis, multiple sclerosis and hormone abnormalities) have been targeted via intravenous (i.v.), subcutaneous (s.c.) or oral routes of administration. Given the ...
Source: Advanced Drug Delivery Reviews - August 10, 2009 Category: Drugs & Pharmacology Authors: Gaspar RS, Duncan R Tags: Adv Drug Deliv Rev Source Type: journals

Design and development of IT-101, a cyclodextrin-containing polymer conjugate of camptothecin.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
IT-101 (Insert Therapeutics-101) is a linear, cyclodextrin-containing polymer conjugate of camptothecin (CPT). When formulated properly, the polymer conjugate self-assembles into nanoparticles of ca. 30 nm diameter and near neutral zeta potential. The nanoparticles show long circulation half-lives in animals and humans and localize in tumors. The nanoparticles enter tumor cells and slowly release the CPT causing them to disassemble into individual polymer chains that are sufficiently small to be cleared renally. IT-101 is currently being investigated in human clinical trials. Here, the design and development of IT-101 ...
Source: Advanced Drug Delivery Reviews - August 10, 2009 Category: Drugs & Pharmacology Authors: Davis ME Tags: Adv Drug Deliv Rev Source Type: journals

Functional polymers as therapeutic agents: Concept to market place.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biologically active synthetic polymers have received considerable scientific interest and attention in recent years for their potential as promising novel therapeutic agents to treat human diseases. Although a significant amount of research has been carried out involving polymer-linked drugs as targeted and sustained release drug delivery systems and prodrugs, examples on bioactive polymers that exhibit intrinsic therapeutic properties are relatively less. Several appealing characteristics of synthetic polymers including high molecular weight, molecular architecture, and controlled polydispersity can all be utilized to...
Source: Advanced Drug Delivery Reviews - August 10, 2009 Category: Drugs & Pharmacology Authors: Dhal PK, Polomoscanik SC, Avila LZ, Holmes-Farley SR, Miller RJ Tags: Adv Drug Deliv Rev Source Type: journals

Polymer Therapeutics: Clinical applications and challenges for development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19682516 [PubMed - as supplied by publisher] (Source: Advanced Drug Delivery Reviews)
Source: Advanced Drug Delivery Reviews - August 10, 2009 Category: Drugs & Pharmacology Authors: Vicent MJ, Ringsdorf H, Duncan R Tags: Adv Drug Deliv Rev Source Type: journals

XMT-1001, a novel polymeric camptothecin pro-drug in clinical development for patients with advanced cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
An overview of XMT-1001 is provided in the context of other topoisomerase I inhibitors conjugated to polymers or encapsulated in liposomes. XMT-1001 is a novel polymeric pro-drug derivative of camptothecin (CPT) with a molecular weight of 70 kDa, in which CPT is chemically tethered to a hydrophilic, bio-degradable polyacetal polymer, poly (1-hydroxymethylene hydroxymethyl formal), also called PHF or Fleximer (R). XMT-1001 releases CPT via intermediates camptothecin-20-O-(N-succinimidoglycinate) (CPT-SI), and camptothecin-20-O-(N-succinamidoyl-glycinate) (CPT-SA) over an extended time period. XMT-1001 has an improved th...
Source: Advanced Drug Delivery Reviews - August 10, 2009 Category: Drugs & Pharmacology Authors: Yurkovetskiy AV, Fram RJ Tags: Adv Drug Deliv Rev Source Type: journals