Antisense oligonucleotides in cutaneous therapy.

Antisense oligonucleotides have been the subject of intense interest as research tools to elucidate the functions of gene products and as therapeutic agents. Initially, their mode of action was poorly understood and the biological effects of oligonucleotides were often misinterpreted. However, research into these gene-based inhibitors of cellular action recently has succeeded in realising their exciting potential, particularly as novel therapeutic agents. An emerging application of this technology is in cutaneous therapy. The demand for more effective dermatological drugs will ensure further development of antisense strategies in skin, with key issues being drug delivery, therapeutic target selection, and clinical applicability.     

Intrapulmonary administration of medications.

An increasing number of medications are being administered by inhalation. However, proper dosing, frequency, formulation, and the optimal delivery device remain to be determined for many of these agents. Inhalation therapy has many advantages compared with other routes of administration including achieving a high drug concentration in the lung, lack of systemic adverse effects, ease of administration, and patient convenience. A broad range of patients may benefit from this type of drug delivery. Practitioners must keep abreast of emerging drug administration strategies and new formulations in order to continually improve care for their patients.     

Intrathecal analgesia

Since the first use of intrathecal (IT) drug infusion systems in the early 1980s, these delivery systems have undergone numerous revisions making them more tolerable, easier to program, and longer lasting. Concurrent with technological advances, the indications for IT pump placement have also been continuously evolving, to the point where the most common indication is now noncancer pain. This article provides an evidence-based review of the indications, efficacy, and complications of IT drug therapy for the most commonly administered spinal analgesics.     

Encapsulated ultrasound microbubbles: therapeutic application in drug/gene delivery.

Encapsulated gas microbubbles are well known as ultrasound contrast agents for medical ultrasound imaging. Nonetheless, not only do these microbubbles help to image, but they can also be used as drug/gene carriers. The microbubbles as drug/gene carriers have an average size less than that of red blood cells, i.e. they are capable of penetrating even into the small blood capillaries and releasing drug and genes under the action of ultrasound field. The application of ultrasound and microbubbles to targeted drug and gene delivery has been the subject of intense experimental research. Under exposure of sufficiently high-amplitude ultrasound, these targeted microbubbles would rupture, spewing drugs or genes, which are contained in its encapsulating layer, to targeted cells or tissues. Recently, targeting ligands are attached to the surface of the microbubbles (i.e. targeted-microbubbles), which have been widely used in cardiovascular system and tumor diagnosis and therapy. In this paper, the characterization of novel targeted ultrasonic contrast agents or microbubbles and their potential applications in drug delivery or gene therapy are reviewed.     

Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective.

Antioxidants are emerging as prophylactic and therapeutic agents. These are the agents, which scavenge free radicals otherwise reactive oxygen species and prevent the damage caused by them. Free radicals have been associated with pathogenesis of various disorders like cancer, diabetes, cardiovascular diseases, autoimmune diseases, neurodegenerative disorders and are implicated in aging. Several antioxidants like SOD, CAT, epigallocatechin-3-O-gallate, lycopene, ellagic acid, coenzyme Q10, indole-3-carbinol, genistein, quercetin, vitamin C and vitamin E have been found to be pharmacologically active as prophylactic and therapeutic agents for above mentioned diseases. Antioxidants are part of diet but their bioavailability through dietary supplementation depends on several factors. This major drawback of dietary agents may be due to one or many of the several factors like poor solubility, inefficient permeability, instability due to storage of food, first pass effect and GI degradation. Conventional dosage forms may not result in efficient formulation owing to their poor biopharmaceutical properties. Principles of novel drug delivery systems need to be applied to significantly improve the performance of antioxidants. Novel drug delivery systems (NDDS) would also help in delivery of these antioxidants by oral route, as this route is of prime importance when antioxidants are intended for prophylactic purpose. Implication of NDDS for the delivery of antioxidants is largely governed by physicochemical characteristics, biopharmaceutical properties and pharmacokinetic parameters of the antioxidant to be formulated. Recently, chemical modifications, coupling agents, liposomes, microparticles, nanoparticles and gel-based systems have been explored for the delivery of these difficult to deliver molecules. Results from several studies conducted across the globe are positive and provided us with new anticipation for the improvement of human healthcare.     

“Nanoantibiotics”: A new paradigm for treating infectious diseases using nanomaterials in the antibiotics resistant era

Despite the fact that we live in an era of advanced and innovative technologies for elucidating underlying mechanisms of diseases and molecularly designing new drugs, infectious diseases continue to be one of the greatest health challenges worldwide. The main drawbacks for conventional antimicrobial agents are the development of multiple drug resistance and adverse side effects. Drug resistance enforces high dose administration of antibiotics, often generating intolerable toxicity, development of new antibiotics, and requests for significant economic, labor, and time investments. Recently, nontraditional antibiotic agents have been of tremendous interest in overcoming resistance that is developed by several pathogenic microorganisms against most of the commonly used antibiotics. Especially, several classes of antimicrobial nanoparticles (NPs) and nanosized carriers for antibiotics delivery have proven their effectiveness for treating infectious diseases, including antibiotics resistant ones, in vitro as well as in animal models. This review summarizes emerging efforts in combating against infectious diseases, particularly using antimicrobial NPs and antibiotics delivery systems as new tools to tackle the current challenges in treating infectious diseases.     

Prevention of Restenosis by Local Drug Delivery

Local drug therapy for preventing restenosis after angioplasty has been investigated for over a decade. Biologically active agents ranging from drugs to genes can be delivered locally using a wide variety of catheters. Microspheres, liposomes, and polymers have been used to enhance drug retention at the delivery site. More recently stents have been investigated as devices to attain local drug delivery, either by coating with polymers, seeding with genetically modified cells or by using them as a source of local radiation. Though the best method of delivering agents locally remains undefined, this approach is likely to emerge as an essential mode of therapy in the near future.     

Intraspinal drug therapy

Intraspinal drug delivery provides agents directly to their site of action. These sites, receptors within the spinal cord, are bound to a greater degree when drugs are administered intraspinally. The purpose for drug therapy, the acute or chronic nature of delivery, and the drug administration system affect the choice of epidural versus intrathecal route of delivery. Pharmacologic properties, such as solubility, pH, and pKa, aid in dictating the drug chosen for administration. Intraspinal opiates and anesthetics have been used extensively since the 1970s in postoperative, postpartum, and cancer populations. Various delivery systems are in use, including external catheters and implanted ports and pumps. Nursing care includes titration of doses, prevention and management of side effects, and maintenance of delivery systems. Intrathecal baclofen is a new treatment for severe spasticity for patients with multiple sclerosis or spinal cord injury. Candidates include patients who experience persistent spasticity unrelieved by antispasmodics or who experience unacceptable side effects to those oral drugs. Nurses assess spasticity, titrate the intrathecal baclofen to obtain an acceptable degree of spasticity, and manage side effects associated with intrathecal baclofen. A long-term benefit of intraspinal drug delivery, potentially providing benefit to many patients, is the identification of experimental agents that do not cross the blood-brain barrier but prove effective when delivered intraspinally. Pharmacologists and others then might undertake the costly modifications necessary to improve the solubility of the drug. The analogue then might be given orally. "The feasibility of an operation is not an indication for its performance." These words, attributed to the late Lord Cohen, also apply to intraspinal drug delivery. As with any therapy, the simplest and least invasive course should be taken. If, for example, the patient experiences good relief without side effects when given oral opiates or baclofen, there is no good rationale for inserting an intraspinal catheter. The potential for increased morbidity and the escalated expense make this an illogical choice. There are, however, many patients who cannot tolerate oral opiates or baclofen but obtain significant benefit from intraspinal drug delivery. Those who benefit should not be denied this therapy. Much research is necessary as this modality develops. Nurses who comprehend the science of intraspinal drug delivery, as well as the art of patient management, can contribute to this advancing field.     

Emerging technologies that overcome biological barriers for therapeutic protein delivery

In the past decade, genomic research and the nascent field of proteomics have exponentially increased the number of potential protein therapeutic molecules for treating medical needs that were previously unmet. To realise the full clinical potential of many of the novel protein drug entities arising from these intense research efforts, emerging protein delivery technologies may be required. Advanced delivery technologies may offer the ability to overcome biochemical and anatomical barriers to protein drug transport, without incurring adverse events, to deliver the agent(s) at a certain desired rate and duration, to protect therapeutic macromolecules from in situ or systemic degradation, as well as increase their therapeutic index by targeting the drug action to a specific site. This review will cover a myriad of novel and emerging technologies that are directed at bypassing biological barriers and that have shown promise in advancing the therapeutic potential of protein drugs.     

Emerging technologies that overcome biological barriers for therapeutic protein delivery

In the past decade, genomic research and the nascent field of proteomics have exponentially increased the number of potential protein therapeutic molecules for treating medical needs that were previously unmet. To realise the full clinical potential of many of the novel protein drug entities arising from these intense research efforts, emerging protein delivery technologies may be required. Advanced delivery technologies may offer the ability to overcome biochemical and anatomical barriers to protein drug transport, without incurring adverse events, to deliver the agent(s) at a certain desired rate and duration, to protect therapeutic macromolecules from in situ or systemic degradation, as well as increase their therapeutic index by targeting the drug action to a specific site. This review will cover a myriad of novel and emerging technologies that are directed at bypassing biological barriers and that have shown promise in advancing the therapeutic potential of protein drugs.     

Nanoscale polymer carriers to deliver chemotherapeutic agents to tumours

Nanoscale polymer carriers have the potential to enhance the therapeutic efficacy of antitumour drugs as they can regulate their release, improve their stability and prolong circulation time by protecting the drug from elimination by phagocytic cells or premature degradation. Moreover, nanoscale polymeric carriers are capable of accumulating in tumour cells and tissues due to enhanced permeability and retention effect or by active targeting bearing ligands designed to recognise overexpressed tumour-associated antigens. The diversity in the polymer structures being studied as drug carriers in cancer therapy allows an optimal solution for a particular drug to be provided regarding its delivery and efficacy, and thus the patient's quality of life. This review is focused on the different types of nanoscale polymer carriers used for the delivery of chemotherapeutic agents and on the factors that affect their cellular uptake and trafficking.     

Therapeutic ultrasound: its application in drug delivery

Ultrasound is best known for its imaging capability in diagnostic medicine. However, there have been considerable efforts recently to develop therapeutic uses for it. The purpose of this review is to summarize some of the recent advances made in the area of therapeutic ultrasound as they relate to drug delivery. In particular, this review will focus on the applications of ultrasound to enhance the delivery and effect of three distinctive therapeutic drug classes: chemotherapeutic, thrombolytic, and gene-based drugs. In addition, ultrasound contrast agents have been recently developed for diagnostic ultrasound. New experimental evidence suggests that these contrast agents can be used as exogenous cavitation nuclei for enhancement of drug and gene delivery. Thus, brief review of this new class of agents and their roles in drug delivery will also be provided. By comparison to diagnostic ultrasound, progress in therapeutic use of ultrasound has been somewhat limited. The recent successes in ultrasound-related drug delivery research positions ultrasound as therapeutic tool for drug delivery in the future.     

Update of Ablative Fractionated Lasers to Enhance Cutaneous Topical Drug Delivery

Ablative fractional lasers (AFXL) enhance uptake of therapeutics and this newly emerging field is called laser-assisted drug delivery (LAD). This new science has emerged over the past decade and is finding its way into clinical practice. LAD is poised to change how medicine delivers drugs. Topical and systemic application of pharmaceutical agents for therapeutic effect is an integral part of medicine. With topical therapy, the stratum corneum barrier of the skin impairs the ability of drugs to enter the body. The purpose of LAD is to alter the stratum corneum, epidermis, and dermis to facilitate increased penetration of a drug, device, or cell to its respected target. AFXL represents an innovative, non-invasive strategy to overcome the epidermal barrier. LAD employs three steps: (1) breakdown of the skin barrier with a laser, (2) optional use a laser for a therapeutic effect, (3) delivery of the medicine through laser channels to further enhance the therapeutic effect. The advantages of using lasers for drug delivery include the ease of accessibility, the non-invasive aspect, and its effectiveness. By changing the laser settings, one may use LAD to have a drug remain locally within the skin or to have systemic delivery. Many drugs are not intended for use in the dermis and so it has yet to be determined which drugs are appropriate for this technique. It appears this developing technology has the ability to be a new delivery system for both localized and systemic delivery of drugs, cells, and other molecules. With responsible development AFXL-assisted drug delivery may become a new important part of medicine.     

Anthracyclines and ellipticines as DNA-damaging anticancer drugs: recent advances

Over the past forty years, anthracyclines and ellipticines have attracted attention as promising cytostatics. In this review, we focus on their mechanisms of cytoxicity, DNA-damaging effects and adverse side-effects. We also summarize ways to enhance the therapeutic effects of these drugs together with a decrease in their adverse effects. Current drug design strategies are focused on drug bioavailability and their tissue targeting, whereas drug delivery to specific intracellular compartments is rarely addressed. Therefore, therapies utilizing the antineoplastic activities of anthracyclines and ellipticines combined with novel strategies such as nanotechnologies for safer drug delivery, as well as strategies based on gene therapy, could significantly contribute to medical practice.     

Recent advances in inflammatory bowel disease

The last decade has seen tremendous advances in our knowledge, which has led to genuine improvements in our understanding of the pathogenesis and management of inflammatory bowel disease (IBD). The combined power of cellular and molecular biology has begun to unveil the enigmas of IBD, and, consequently, substantial gains have been made in the treatment of IBD. Refinements in drug formulation have provided the ability to target distinct sites of delivery, while enhancing the safety and efficacy of older agents. Simultaneous progress in biotechnology has fostered the development of new agents that strategically target pivotal processes in disease pathogenesis. This article addresses our current understanding of the pathogenesis of IBD, including the latest developments in animal models and covers agents currently used in the treatment of IBD as well as emerging therapies.     

Optical molecular imaging: from single cell to patient

Optical imaging is an emerging field with a wide range of biomedical research and clinical applications, both current and future. It comprises several classes of techniques that are capable of providing information at the molecular, cellular, tissue, and whole-animal levels. These techniques match well with emerging genomic and proteomic technologies that enable development of optical "probes," as well as with nanotechnologies for multifunctional imaging and drug delivery. These advances have enormous potential to accelerate drug discovery/development by providing predictive information on mechanisms of action and biological responses.     

Carbon quantum dots and their biomedical and therapeutic applications: a review

In recent years, nano carbon quantum dots (CQDs) have received increasing attention due to their properties such as small size, fluorescence emission, chemical stability, water solubility, easy synthesis, and the possibility of functionalization. CQDs are fluorescent 0D carbon nanostructures with sizes below 10 nm. The fluorescence in CQDs originates from two sources, the fluorescence emission from bandgap transitions of conjugated π-domains and fluorescence from surface defects. The CQDs can emit fluorescence in the near-infrared (NIR) spectral region which makes them appropriate for biomedical applications. The fluorescence in these structures can be tuned with respect to the excitation wavelength. The CQDs have found applications in different areas such as biomedicine, photocatalysis, photosensors, solar energy conversion, light emitting diodes (LEDs), etc. The biomedical applications of CQDs include bioimaging, drug delivery, gene delivery, and cancer therapy. The fluorescent CQDs have low toxicity and other exceptional physicochemical properties in comparison to heavy metals semiconductor quantum dots (QDs) which make them superior candidates for biomedical applications. In this review, the synthesis routes and optical properties of the CQDs are clarified and recent advances in CQDs biomedical applications in bioimaging (in vivo and in vitro), drug delivery, cancer therapy, their potential to pass blood–brain barrier (BBB), and gene delivery are discussed.

The biomedical applications of the recently emerging carbon quantum dots are reviewed.     

Current status of local therapy in malignant gliomas — A clinical review of three selected approaches

Malignant gliomas are the most frequently occurring, devastating primary brain tumors, and are coupled with a poor survival rate. Despite the fact that complete neurosurgical resection of these tumors is impossible in consideration of their infiltrating nature, surgical resection followed by adjuvant therapeutics, including radiation therapy and chemotherapy, is still the current standard therapy. Systemic chemotherapy is restricted by the blood–brain barrier, while methods of local delivery, such as with drug-impregnated wafers, convection-enhanced drug delivery, or direct perilesional injections, present attractive ways to circumvent these barriers. These methods are promising ways for direct delivery of either standard chemotherapeutic or new anti-cancer agents. Several clinical trials showed controversial results relating to the influence of a local delivery of chemotherapy on the survival of patients with both recurrent and newly diagnosed malignant gliomas. Our article will review the development of the drug-impregnated release, as well as convection-enhanced delivery and the direct injection into brain tissue, which has been used predominantly in gene-therapy trials. Further, it will focus on the use of convection-enhanced delivery in the treatment of patients with malignant gliomas, placing special emphasis on potential shortcomings in past clinical trials. Although there is a strong need for new or additional therapeutic strategies in the treatment of malignant gliomas, and although local delivery of chemotherapy in those tumors might be a powerful tool, local therapy is used only sporadically nowadays. Thus, we have to learn from our mistakes in the past and we strongly encourage future developments in this field.     

Special considerations and treatment of patients with HBV-HIV coinfection

Coinfection with HIV and hepatitis B virus (HBV) substantially alters the natural course of HBV infection as well as its management. Therapy for HBV infection in HIV-coinfected patients requires several factors to be taken into consideration, such as whether the antiviral activity of a particular agent is specific for HBV (that is, adefovir, entecavir, telbivudine and pegylated interferon) or for both viruses (that is, lamivudine, emtricitabine and tenofovir), whether the chosen drug has the potential for inducing drug resistance and cross-resistance, and whether use of the agent is associated with hepatotoxicity. For coinfected patients who do not require therapy for their HIV infection, clinicians should avoid prescribing monotherapy with agents that have activity against HIV (that is, tenofovir, entecavir, emtricitabine or lamivudine) so as not to compromise future HIV care. This review discusses the current status of treatment of hepatitis B in the setting of HIV infection. It describes emerging therapeutic strategies and addresses challenges in the treatment of coinfection.