Number Of Delivery Systems Research Articles

Engaging physicians and consumers in conversations about treatment overuse and waste: a short history of the choosing wisely campaign.

Wise management of health care resources is a core tenet of medical professionalism. To support physicians in fulfilling this responsibility and to engage patients in discussions about unnecessary care, tests, and procedures, in April 2012 the American Board of Internal Medicine Foundation, Consumer Reports, and nine medical specialty societies launched the Choosing Wisely campaign. The authors describe the rationale for and history of the campaign, its structure and approach in terms of engaging both physicians and patients, lessons learned, and future steps.In developing the Choosing Wisely campaign, the specialty societies each developed lists of five tests and procedures that physicians and patients should question. Over 50 specialty societies have developed more than 250 evidence-based recommendations, some of which Consumer Reports has "translated" into consumer-friendly language and helped disseminate to tens of millions of consumers. A number of delivery systems, specialty societies, state medical societies, and regional health collaboratives are also advancing the campaign's recommendations. The campaign's success lies in its unique focus on professional values and patient-physician conversations to reduce unnecessary care. Measurement and evaluation of the campaign's impact on attitudinal and behavioral change is needed.

Concise Review: Clinical Translation of Wound Healing Therapies Based on Mesenchymal Stem Cells

There is enormous worldwide demand for therapies to promote the efficient resolution of hard-to-heal wounds with minimal appearance of scarring. Recent in vitro studies with mesenchymal stem cells (MSCs) have identified numerous mechanisms by which these cells can promote the process of wound healing, and there is significant interest in the clinical translation of an MSC-based therapy to promote dermal regeneration. This review provides a systematic analysis of recent preclinical and clinical research to evaluate the use of MSCs in wound healing applications. These in vivo studies provide overwhelming evidence that MSCs can accelerate wound closure by modulating the inflammatory environment, promoting the formation of a well-vascularized granulation matrix, encouraging the migration of keratinocytes, and inhibiting apoptosis of wound healing cells. The trophic effects of MSC therapy also appear to augment wound healing in diabetic tissues, thereby preventing the formation of nonhealing ulcers. Finally, a number of delivery systems have been evaluated and indicate that MSCs could be the basis of a versatile therapy to fulfill the clinical needs for dermal regeneration. However, despite the apparent advantages of MSC-based therapies, there have been only limited clinical investigations of this type of therapy in humans. Thus, our review concludes with a discussion of the translational barriers that are limiting the widespread clinical use of MSCs to enhance wound healing.

Efficient siRNA Delivery with Non-viral Polymeric Vehicles

Sequence-specific gene silencing using small interfering RNA (siRNA) provides a potent and specific method for gene expression, thus is now being evaluated in clinical trials as a novel therapeutic strategy. As a results, there has been a significant surge of interest in the application of siRNA in therapeutics as a means of silencing the specific gene function. However, for siRNA technology to be valuable and effective, the development of efficient siRNA delivery strategy is essential for improving biological activities such as stability, cellular uptake, sequence-specificity, devoid of nonspecific knockdown and toxic side effects. Accordingly, a number of delivery systems, both viral and nonviral, have been reported and some of them successfully used for the introduction of siRNA into cells both in vitro and in vivo. Here, we discuss the current understanding of synthetic siRNA delivery mechanism and strategies of siRNA delivery by non-viral polymeric vehicles which are currently used in vitro and in vivo.

Induction of interleukin-6 in human retinal epithelial cells by an attenuated Herpes simplex virus vector requires viral replication and NFκB activation

Gene delivery has potential for treating ocular disease and a number of delivery systems have been tested in animal models. However, several viral vectors have been shown to trigger undesirable transient inflammatory responses in the eye. Previously, it was shown that an attenuated Herpes simplex virus vector (hrR3) transduced numerous cell types in the anterior and posterior segments of monkey eyes, but this was accompanied by inflammation. In the retina, retinal pigment epithelial cells were the predominant cell type transduced by hrR3. IL-6 is an important pro-inflammatory cytokine and may play a role in the response to the hrR3 vector. Infection of human ARPE-19 cells with hrR3 resulted in increased IL-6 expression and secretion 3–4h post-infection. In the presence of acyclovir (70μM) or in cells infected with UV-inactivated hrR3, IL-6 was not up-regulated indicating viral replication was required. Expression of the HSV-1 α and β genes may be necessary but was not sufficient for NF-κB activation and IL-6 up-regulation. The translocation of NF-κB into the nucleus also occurred between 3 and 4h post-infection, coincident with increased IL-6 expression. Inhibition of NF-κB translocation by an Adenovirus vector expressing a dominant negative IκB (AdIκBam) inhibited IL-6 up-regulation, indicating that NF-κB plays a role in increasing IL-6 expression in APRE-19 cells. The hrR3 virus lacks viral ribonucleotide reductase (RR) activity, thus RR is not required for NF-κB activation or IL-6 up-regulation in ARPE-19 cells.

Molecular conjugates: a targeted gene delivery vector for molecular medicine.

The use of gene therapy to treat diseases of both genetic and infectious origins has increased rapidly over the past 5 years. Accordingly, the number of delivery systems, based on either recombinant viruses or nonviral vectors, has also increased. As a result most research in this field continues to be in the area of vector development. Crucial to this aspect is the development of efficient, multipurpose therapeutic gene delivery systems which should have, but not be limited to, the following characteristics: (a) the ability to target specific cells, (b) no limitation on the size or the type of nucleic acid that can be delivered, (c) no intact viral component and therefore safe for the recipient, (d) the ability to transduce a large number of cells regardless of the mitotic status; and (e) the potential to be completely synthetic. As a step toward the development of this type of delivery system, molecular conjugates have been created. Molecular conjugates are ligands to which a nucleic acid or DNA-binding agent has been attached for the specific targeting of nucleic acids (i.e., plasmid DNA) to cells. The resulting protein/DNA complex can consist of at least four components: (a) a ligand for cell-specific targeting and receptor-mediated endocytosis, (b) a nucleic acid or DNA-binding agent (than is chemically attached to the ligand) for the binding of the DNA by ionic or other nondamaging interactions, (c) a nucleic acid, i.e., a plasmid for gene expression, and (d) an endosomal lysis agent to enhance the re-

Delivery systems for the administration of drugs to the periodontal pocket

A number of delivery systems have been investigated for administration of antibacterial agents in the treatment of plaque-initiated periodontal disease. These include prolonged release intrapocket devices which are inserted at diseased sites. An effective antibacterial concentration is maintained if drug lost by elimination processes is replaced. Bioassays or sensitive HPLC assays may be used to monitor drug concentrations in the gingival crevicular fluid and allow estimation of the duration of effective release. Non-degradable and degradable systems have been developed, and although improvements in clinical and microbiological parameters are reported with both these systems, advantages have been identified with the degradable systems. Importantly, depleted degradable devices do not require removal at the end of treatment, but repeated administration is generally required, as these systems mostly produce effective drug concentrations for short periods. To improve this method of drug administration the aims and optimal duration of treatment need to be further clarified so that development of delivery system can occur through modification of the device's release and degradation characteristics.