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Delivery Mechanism (delivery + mechanism)
Selected AbstractsDesigned Multifunctional Nanocomposites for Biomedical ApplicationsADVANCED FUNCTIONAL MATERIALS, Issue 10 2010Humphrey H. P. Yiu Abstract The assembly of multifunctional nanocomposite materials is demonstrated by exploiting the molecular sieving property of SBA-16 nanoporous silica and using it as a template material. The cages of the pore networks are used to host iron oxide magnetic nanoparticles, leaving a pore volume of 0.29,cm3,g,1 accessible for drug storage. This iron oxide,silica nanocomposite is then functionalized with amine groups. Finally the outside of the particle is decorated with antibodies. Since the size of many protein molecules, including that of antibodies, is too large to enter the pore system of SBA-16, the amine groups inside the pores are preserved for drug binding. This is proven using a fluorescent protein, fluorescein-isothiocyanate-labeled bovine serum albumin (FITC-BSA), with the unreacted amine groups inside the pores dyed with rhodamine B isothiocyanate (RITC). The resulting nanocomposite material offers a dual-targeting drug delivery mechanism, i.e., magnetic and antibody-targeting, while the functionalization approach is extendable to other applications, e.g., fluorescence,magnetic dual-imaging diagnosis. [source] Early osteoblastic differentiation induced by dexamethasone enhances adenoviral gene delivery to marrow stromal cellsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2004Jeremy S. Blum Abstract We investigated the implications of induced osteogenic differentiation on gene delivery in multipotent rat marrow stromal cells (MSCs). Prior to genetic manipulation cells were cultured with or without osteogenic supplements (5 ± 10,8 M dexamethasone, 160 ,M l-ascorbic acid 2-phosphate, and 10 mM ,-glycerophosphate). Comparison of liposome, retroviral, and adenoviral vectors demonstrated that all three vectors could mediate gene delivery to primary rat MSCs. When these vectors were applied in the absence or presence of osteogenic supplements, we found that MSCs differentiated prior to transduction with adenovirus type 5 vectors produced a 300% increase in transgene expression compared to MSCs that were not exposed to osteogenic supplements. This differentiation effect appeared specific to adenoviral mediated gene delivery, since there was minimal increase in retroviral gene delivery and no increase in liposome gene delivery when MSCs were treated with osteogenic supplements. In addition, we also determined this increase in transgene production to occur at a higher concentration of dexamethasone (5 ± 10,8 M) in the culture medium of MSCs prior to adenoviral transduction. We found that this increased transgene production could be extended to the osteogenic protein, human bone morphogenetic protein 2 (hBMP-2). When delivered by an adenoviral vector, hBMP-2 transgene production could be increased from 1.4 ng/105 cells/3 days to 4.3 ng/105 cells/3 days by culture of MSCs with osteogenic supplements prior to transduction. These results indicate that the utility of MSCs as a therapeutic protein delivery mechanism through genetic manipulation can be enhanced by pre-culture of these cells with dexamethasone. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Deep percutaneous penetration into muscles and jointsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2006Christine M. Lee Abstract The transdermal absorption of drugs and its subsequent deep tissue delivery is a complex process, with many factors influencing the penetration mechanisms. Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used in the treatment of joint and muscle diseases. However, the dangers associated with oral medications highlight the need for alternative methods of targeting and retaining drugs; one such means is through topical delivery. The drug's lipophilicity, permeability, and fraction unbound found in the viable skin are some physiochemical factors influencing the delivery mechanism after transdermal absorption. These and other variables play a role in determining whether the drug reaches the deep tissues via direct penetration or from systemic redistribution. Pharmacokinetic models have been developed to help elucidate the penetration routes and efficacy for various drugs. While there are still uncertainties regarding the deep tissue penetration kinetics, improvements to current research methodologies may bring about a greater understanding of percutaneous absorption into the deep muscle and joints. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1405,1413, 2006 [source] What are the nursing implications when using paliperidone prolonged release for people with schizophreniaJOURNAL OF PSYCHIATRIC & MENTAL HEALTH NURSING, Issue 10 2008A. JONES rn phd Paliperidone prolonged release (PR) is a new product licensed for the treatment of schizophrenia. It is the active metabolite of risperidone, a drug that has been successfully used in the treatment of schizophrenia and mood disorder. Paliperidone PR has a unique pharmacological delivery mechanism that may incur benefits for particular patients diagnosed with schizophrenia. Studies investigating paliperidone PR are reviewed along with implications for its use by nurse prescribers and those nurses who monitor the use of medication for people with psychosis. [source] Topical application of acidified nitrite to the nail renders it antifungal and causes nitrosation of cysteine groups in the nail plateBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2007M.J. Finnen Summary Background, Topical treatment of nail diseases is hampered by the nail plate barrier, consisting of dense cross-linked keratin fibres held together by cysteine-rich proteins and disulphide bonds, which prevents penetration of antifungal agents to the focus of fungal infection. Acidified nitrite is an effective treatment for tinea pedis. It releases nitric oxide (NO) and other NO-related species. NO can react with thiol (-SH) groups to form nitrosothiols (-SNO). Objectives, To determine whether acidified nitrite can penetrate the nail barrier and cure onychomycosis, and to determine whether nitrosospecies can bind to the nail plate. Methods, Nails were treated with a mixture of citric acid and sodium nitrite in a molar ratio of 0·54 at either low dose (0·75%/0·5%) or high dose (13·5%/9%). Immunohistochemistry, ultraviolet-visible absorbance spectroscopy and serial chemical reduction of nitrosospecies followed by chemiluminescent detection of NO were used to measure nitrosospecies. Acidified nitrite-treated nails and the nitrosothiols S-nitrosopenicillamine (SNAP) and S-nitrosoglutathione (GSNO) were added to Trichophyton rubrum and T. mentagrophytes cultures in liquid Sabouraud medium and growth measured 3 days later. Thirteen patients with positive mycological cultures for Trichophyton or Fusarium species were treated with topical acidified nitrite for 16 weeks. Repeat mycological examination was performed during this treatment time. Results, S-nitrothiols were formed in the nail following a single treatment of low- or high-dose sodium nitrite and citric acid. Repeated exposure to high-dose acidified nitrite led to additional formation of N-nitrosated species. S-nitrosothiol formation caused the nail to become antifungal to T. rubrum and T. mentagrophytes. Antifungal activity was Cu2+ sensitive. The nitrosothiols SNAP and GSNO were also found to be antifungal. Topical acidified nitrite treatment of patients with onychomycosis resulted in > 90% becoming culture negative for T. rubrum. Conclusions, Acidified nitrite cream results in the formation of S-nitrosocysteine throughout the treated nail. Acidified nitrite treatment makes a nail antifungal. S-nitrosothiols, formed by nitrosation of nail sulphur residues, are the active component. Acidified nitrite exploits the nature of the nail barrier and utilizes it as a means of delivery of NO/nitrosothiol-mediated antifungal activity. Thus the principal obstacle to therapy in the nail becomes an effective delivery mechanism. [source] Innovations in oligonucleotide drug deliveryJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2003Melanie A. Lysik Abstract Oligonucleotides (ONs) are a new class of therapeutic compounds under investigation for the treatment of a variety of disease states, such as cancer and HIV, and for FDA approval of an anti-CMV retinitis antisense molecule (VitraveneÔ, Isis Pharmaceuticals). However, these molecules are limited not only by poor cellular uptake, but also by a general lack of understanding regarding the mechanism(s) of ON cellular uptake. As a result, various delivery vehicles have been developed that circumvent the proposed mechanism of uptake, endocytosis, while improving target specific delivery and/or drug stability. This review describes various traditional and novel delivery mechanisms that have been employed to improve ON cellular delivery, cost effectiveness, and therapeutic efficacy. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:1559,1573, 2003 [source] Sequential model of phage PRD1 DNA delivery: active involvement of the viral membraneMOLECULAR MICROBIOLOGY, Issue 5 2002A. Marika Grahn Summary DNA translocation across the barriers of recipient cells is not well understood. Viral DNA delivery mechanisms offer an opportunity to obtain useful information in systems in which the process can be arrested to a number of stages. PRD1 is an icosahedral double-stranded (ds)DNA bacterial virus with an internal membrane. It is an atypical dsDNA phage, as any of the vertex spikes can be used for receptor recognition. In this report, we dissect the PRD1 DNA entry into a number of steps: (i) outer membrane (OM) penetration; (ii) peptidoglycan digestion; (iii) cytoplasmic membrane (CM) penetration; and (iv) DNA translocation. We present a model for PRD1 DNA entry proposing that the initial stage of entry is powered by the pressure build-up during DNA packaging. The viral protein P11 is shown to function as the first DNA delivery protein needed to penetrate the OM. We also report a DNA translocation machinery composed of at least three viral integral membrane proteins, P14, P18 and P32. [source] The Big Questions of Public Administration EducationPUBLIC ADMINISTRATION REVIEW, Issue 5 2001Robert B. Denhardt Following Behn's observation that scientists in other fields understand the big questions of their disciplines and focus attention and their discussions on those questions, public administration scholars have attempted to identify the "big questions" in public management and public administration. In this article, I suggest that scholars in public administration should also be attentive to the big questions of public administration education, those timeless and enduring concerns that speak to the basic perspectives that we bring to the educational process. Specifically, I identify four big questions: Do we seek to educate our students with respect to theory or to practice? Do we prepare students for their first jobs or for those to which they might aspire later? What are the appropriate delivery mechanisms for MPA courses and curricula? What personal commitments do we make as public administration educators? I argue that these big questions in public administration education are far more connected than we usually think, and by posing these questions in terms of processes of human development we can at least provide a framework through which we might develop more coherent answers to these big questions, answers that recognize and build on the diversity of our students and our faculty. [source] | |||||||||||||