Current Bioactive Compounds - Volume 5, Issue 3, 2009

It is our honor and privilege to serve as the Guest Editors of the Special Edition on “Nanostructures for Therapeutic Applications” for the journal “Current Bioactive Compounds”. The past decade has witnessed an unprecedented growth in the area of nanotechnology. This in turn has provided valuable tools to understand the biological systems and processes at a much closer level than was previously possible. The combination of nanotechnology and biology has also led to the development of a new generation of therapeutic devices with high therapeutic efficacy. This is mainly due to their ability to precisely interact with the sub-microscopic structures of living cells. The aim of the special edition is to provide a state-of-the-art, comprehensive account of the recent advances towards developing nanostructures for four different therapeutic applications. The article by Peach et al. discusses the recent developments in the nanotechnological approaches for the treatment of cancer. The authors provide an overview of the passive, active and external tumor targeting strategies using nanoparticle (NP) delivery systems. The article by Freeman et al., overviews the recent developments in the nanofabrication processes for promoting musculoskeletal tissue regeneration. The article discusses the various nanostructures currently been developed to modulate musculoskeletal cell functions to promote regeneration. The article by Wang et al., highlights the various unique nanostructures capable of by-passing the blood-brain barrier, a feat difficult to achieve using conventional therapeutic strategies. Finally, the article by Neal et al., presents an overview of the applications of nanomedicine to promote cardiovascular tissue regeneration. The guest editors would like to express their sincere gratitude to the editorial board of the Current Bioactive Compounds for their support. We would also like to appreciate all the authors for their valuable contributions in making this special edition a success.

Cancer is currently responsible for approximately one quarter of all deaths each year in the United States [1]. Decades of refinement to cancer treatment has led to a multimodal approach, which combines surgery with radiation and/or chemotherapy. However, aggressive and advanced stages of cancer are only slightly hindered with drugs and radiation at the cost of considerable patient morbidity. Implementation of nanotechnology can increase the potency and decrease the side effects of chemotherapeutic agents by specifically targeting cancerous tissue. Most nanotechnologies available in the clinical market are nanoparticle (NP) based drug delivery vehicles, which attests to the promise for cancer chemotherapy applications. There is a constantly growing list of materials and synthetic techniques that allow for the creation of NPs with different compositions, sizes, charge, architecture, biodegradability and surface moieties, all of which can be adjusted within each class of particle. Ultimately this design freedom can be utilized to take advantage of cancer pathophysiology and specifically target cancerous tissue. When synthesized to a certain size, NPs delivered systemically can exploit the leaky vasculature of cancerous tumors and passively target the desired cancerous tissue. More precision may be gained by attaching ligands that actively target surface moieties that are expressed to a greater extent by cancer. This review summarizes the progress made in the past 5 years in NP chemotherapeutic delivery with a focus on unique applications of passive, active and external targeting strategies followed by a discussion on what strategy is optimal for cancer chemotherapy.

The use of nanoscale structures and features is becoming increasingly popular in tissue engineering, and for good reason. Devices that have features in the nano-length scale offer many benefits that their counterparts do not. These features can alter cellular behavior including cell attachment, degree of cell spreading, and cellular alignment. These properties affect the arrangement of extracellular matrix material produced by attached cells. Nano to micro-scale porosity is important for cellular infiltration into long term or degradable implants. Features of this length scale model the structures that cells typically see in vivo, therefore they tend to respond positively when placed on nano length structures. The inclusion of nanoscale features or use of nanoscale structures improves the cellular response to the implant and increases tissue bonding thereby reducing the chances of implant failure. Nanoscale structures can also enhance device strength; by combining nanoscale, high moduli particles with more flexible, weaker materials one can create high strength composites for bone tissue engineering. There are a host of ways to create nanostructures or create nanoscale features on an implant including electrospinning, nanoetching, and the creation of nanospheres. They all produce roughness, pores, or alignment in the nanoscale which is essential for tissue engineering success. These techniques encompass a wide range of materials and methods. Several of these techniques and their applications will be discussed in this paper.

The Blood Brain Barrier (BBB) represents a fundamental challenge towards development of therapy for disease in the brain such as brain tumor, Parkinson's disease and Alzheimer's disease. The passage across the BBB is vital to the success of a therapeutic platform and nanotechnology based systems provide great potential for solving the problem. This chapter discusses the structures and functions of the BBB, the transport mechanisms at the BBB, the strategies for crossing the BBB, and nanostructures for delivering drugs and imaging in the brain.

Cardiovascular disease is becoming an increasingly significant problem. In attempts to overcome many of the traditional hurdles of cardiovascular disease treatment, therapeutic approaches have been gradually moving beyond an exclusive focus on orally delivered drugs towards the development of nanoscale applications. These technologies exploit molecular scale events to improve drug and gene delivery applications, enhance preventative medicine and diagnostic strategies, and create biomimicking substrates for vascular tissue engineering. As nanoscale treatments enter the arena of clinical medicine, new ways of thinking about and routes for applying nanomedicine to cardiovascular health issues are emerging. With focuses on drug delivery, gene therapy, and biomimetics, this article will provide a comprehensive review of various nanomedicine applications for combating atherosclerosis and for improving upon current vascular tissue engineering designs.

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Several Chrysobalanaceae family members are considered medicinal plants in South America and their infusions have been widely used to treat several diseases, such as diabetes and hypertension. Methanolic extract from the leaves of Licania pittieri (Chrysobalanaceae), has previously shown hypotensive effect in anaesthetized normotensive rats. The aim of this study was to identify the compounds present in the methanolic extract of L. pittieri that could be responsible for the hypotensive effect. Bioactivity-guided fractionation of this extract was done by monitoring the changes induced on mean arterial blood pressure and heart rate on normotensive rats, which led to the isolation of three known compounds identified by NMR spectroscopy methods as pomolic acid, quercetin and astilbin. Pomolic acid (0.4 mg/kg, i.v.) diminished mean arterial blood pressure (24.1 %) for more than 45 minutes and also heart rate (38.7 %), while quercetin and astilbin (4 mg/Kg each, i.v.) showed a weak and transient hypotensive effect. In addition, the observation of nose bleeding in pomolic acid-treated rats led us to investigate its effects on hemostasis. Pomolic acid proved to be a potent inhibitor of the aggregation of human platelets induced by ADP and Epinephrine, exhibited IC50 values close to 60 nM and 20 nM, respectively. In contrast, pomolic acid did not inhibit human platelet aggregation induced by PAF, collagen, U46619 (thromboxane analogue), TRAP or arachidonic acid. These results showed for the first time the hypotensive and platelet anti-aggregating effects of pomolic acid and suggested its potential role in cardiovascular therapy.

Lactoferrin (Lf) is present in milk and gland secretions and serve as an antimicrobial function. Insufficient amounts of Lf in some secretions also appear to correlate with certain health problems. Protection against gastroenteritis is the most likely biologically relevant activity of lactoferrin. Multiple in vitro and animal studies have shown a protective effect of lactoferrin on infections with enteric microorganisms, including rotavirus, Giardia, Shigella, Salmonella and the diarrheagenic Escherichia coli. Lactoferrin has two major effects on enteric pathogens: it inhibits growth and it impairs function of surface expressed virulence factors thereby decreasing their ability to adhere or to invade mammalian cells. Lf also inhibits several species of fungi and certain parasites. This review covers the role of Lf in clearing the parasitic infections. The mechanism by which lactoferrin inhibits some parasites may be via stimulation of the process of phagocytosis, whereby immune cells engulf and digest foreign organisms. Trichomonas vaginalis is a protozoan responsible for the number one, non-viral sexually transmitted disease. In this review, we also discussed the role of Lf in cervical infections.

Licorice as a kind of traditional Chinese medicine is widely used for more than one thousand years. Modern studies show that Licorice has antibacterial, antiviral, antioxidant, and other pharmacological effects. In recent years, the anti-tumor effect of Licorice has evoked the great interest due to its bioactive ingredients. The most active ingredients in Licorice mainly include triterpenes, flavonoids, polysaccharides, and so on. In this review, a comprehensive overview on the active ingredients of Glycyrrhiza and its antitumor mechanism was addressed.