Nanomedicine and drug delivery

This article discusses the use of nanotechnology in drug delivery approaches. Magnetic nanotechnology is finding wide applications in medicine, most notably in MRI and magnetic separation. The impedance biosensor is expected to find applications in monitoring cytokines in cancer, bone turnover markers in osteoporosis, and understanding neural-degenerative diseases.     

Neonatal drug monitoring and drug delivery systems

The problems associated with drug delivery and achievement of therapeutic blood levels in neonates are reviewed, using chloramphenicol as an example. Administration of small volumes, concentrated solutions and intravenous line filter chambers greatly affect the final dose delivered to the infant. Once delivered, variability in drug elimination caused by changing hepatic and renal function and protein binding necessitate careful drug monitoring and pharmacokinetic analysis especially with drugs like chloramphenicol that have a narrow therapeutic range. If one uses a team approach involving nurses, clinical chemists and clinical pharmacologists, optimal doses of chloramphenicol in the newborn are achieved more consistently.     

Spinal drug delivery

Clinicians currently base decisions regarding the use of intrathecal drug therapy for chronic pain on reports from uncontrolled and retrospective studies that fail to rely on standardized outcome measures. In this article, we summarize what is known about currently administered intrathecal therapies, including opioids, gamma-aminobutyric acid agonists, alpha-2 adrenoreceptor agonists, local anesthetics (sodium channel antagonists), calcium channel antagonists, miscellaneous agents, and drug combination therapy. In addition, we offer a brief look at novel approaches that may revolutionize intrathecal drug delivery.     

Noninvasive drug delivery

Advances in biopharmaceutical technology have spawned new drug delivery devices and mechanisms. Noninvasive methods, including iontophoresis and transmucosal drug delivery, have improved treatment of certain patient population. Their use is discussed in the following paper.     

Nasal drug delivery

The Nasal Drug Delivery Conference was held at the Institute of Directors in London, England. The meeting was organised by the Management Forum Ltd and chaired by P Seeney (PA Consulting, UK) and Professor F Merkus (Leiden University, The Netherlands; Innoscience Technology, Belgium). The conference covered a wide range of topics including aspects of nasal physiology, formulation, new nasal products, nasal vaccines, nose to brain transport and pain management via nasal sprays.     

Photochemical drug and gene delivery

The utilization of macromolecules in the therapy of cancer and other diseases is becoming increasingly relevant. Recent advances in molecular biology and biotechnology have made it possible to improve the targeting and design of cytotoxic agents or DNA complexes for clinical applications. In many cases, to achieve the desired biological effect of these macromolecules, internalization to the cell cytosol is crucial. Although new delivery systems have improved the cellular uptake of macromolecules, tissue penetration, cellular uptake and efficient transfer of the molecules into the cytosol of target cells are still fundamental obstacles. At an intracellular level, the greatest obstruction for cytosolic release of the therapeutic molecule is the membrane barrier of endocytic vesicles. Photochemical activation and delivery of drugs and genes are novel technologies to overcome these obstacles. The background theory to these technologies is described in this review and recent data in this field are discussed.     

Innovations in drug delivery

With recent innovations in pharmaceutical technology, important new methods of drug delivery have joined established ones. Prolonged-release oral preparations can provide precisely controlled drug delivery, which permits less frequent dosage of drugs with a short elimination half-life and thus improves compliance. These preparations also can narrow fluctuations in plasma levels, which maximizes efficacy and minimizes toxicity. Sustained-release intraocular and transcutaneous preparations offer similar advantages. Infusion pumps provide predictable systemic delivery of drugs that cannot be given orally or transcutaneously. Further innovations can undoubtedly be expected. When the therapeutic alternatives include a prolonged-release preparation, its potential advantages should be weighed against its potential disadvantages. Although some of these preparations cost more, this disadvantage may be outweighed by potential advantages.     

Novel drug delivery systems

Interest in pain management is growing, with the emerging demand by our patients and colleagues, for pain relief. To meet that need, pharmaceutical and medical technology companies have provided the medical field with a variety of choices and options to deliver medication for pain control. Examination and review of the present systemic options are introduced. A more detailed look at the intrathecal route is necessary because of the tremendous potential for receptor-targeted drug delivery. The ability to treat nociceptive and neuropathic pain with drug-specific therapy makes this system all the more exciting. Because of this future, a wealth of new and old drugs are being found or reexamined for their use.     

Liposomal drug delivery.

Liposomes are composed of phospholipids, the basic components of human cell walls. Liposome encapsulation improves a medication's bioavailability, which can extend treatment effects and reduce drug dosing. The therapeutic advantages of liposomal drug delivery, such as the ability of long-circulating liposomes to accumulate preferentially at disease sites, including tumors and sites of inflammation, are well recognized. In cases in which a single active has more than one liposome product available, formulation changes leading to differences in pharmacokinetics, toxicity, and clinical efficacy are described.     

Development of an antisense RNA delivery system using conjugates of the MS2 bacteriophage capsids and HIV-1 TAT cell penetrating peptide

RNA-based therapeutic strategies are used widely due to their highly specific mode of action. However, the major obstacle in any RNA-based therapy is cellular delivery and stability in the cells. The self-assembly of the MS2 bacteriophage capsids has been used to develop virus-like particles (VLPs) for drug delivery. In this study, we utilized the heterobifunctional crosslinker, sulfosuccinimidyl-4-(p-maleimidophenyl)-butyrate (sulfo-SMPB), to conjugate the human immunodeficiency virus-1 (HIV-1) Tat peptide and MS2 VLPs; the antisense RNA against the 5′-untranslated region (UTR) and the internal ribosome entry site (IRES) of the hepatitis C virus (HCV) was packaged into these particles by using a two-plasmid coexpression system. The MS2 VLPs conjugated with the Tat peptide were then transferred into Huh-7 cells containing an HCV reporter system. The packaged antisense RNA showed an inhibitory effect on the translation of HCV. This paper describes our initial results with this system using the Tat peptide.     

Microchip technology in drug delivery

The realization that the therapeutic efficacy of certain drugs can be affected dramatically by the way in which they are delivered has created immense interest in controlled drug delivery systems. Much previous work in drug delivery focused on achieving sustained drug release rates over time, while a more recent trend is to make devices that allow the release rate to be varied over time. Advances in microfabrication technology have made an entirely new type of drug delivery device possible. Proof-of-principle experiments have shown that silicon microchips have the ability to store and release multiple chemicals on demand. Future integration of active control electronics, such as microprocessors, remote control units, or biosensors, could lead to the development of a ‘pharmacy on a chip,’ ie ‘smart’ microchip implants or tablets that release drugs into the body automatically when needed.