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Local drug delivery

Jinke Xu, Mifong Tam, Sepideh Samadei, Sophie Lerouge, Jake Barralet, Mary M Stevenson, Marta Cerruti
Mucoadhesive drug delivery systems stick to mucosal tissues and prolong the local retention time of drugs. Since the colon is covered by a mucosal layer, mucoadhesive rectal formulations may improve treatment of such diseases as hypertension or colon cancer. Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic inflammation of the colonic mucosa. It is commonly treated with sulfasalazine (SSZ), which is metabolized by the intestinal flora into the therapeutic 5-aminosalicylic acid (5-ASA) and a toxic by-product sulfapyridine (SP)...
October 18, 2016: Acta Biomaterialia
Roberto Gandini, Costantino Del Giudice
OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of percutaneous catheter-delivered ultrasound energy to improve local paclitaxel delivery effects in patients with critical limb ischemia (CLI) treated for femoral-popliteal arterial disease. BACKGROUND: Treatment of patients with CLI continues to be the greatest challenge in peripheral artery disease; in particular, treatment of femoral-popliteal chronic total occlusion is characterized by poor primary patency...
October 24, 2016: JACC. Cardiovascular Interventions
M Hrubý, J Kučka, J Pánek, P Štěpánek
For many important research topics in polymer science the use of radionuclides brings significant benefits concerning nanotechnology, polymer drug delivery systems, tissue engineering etc. This contribution describes important achievements of the radionuclide laboratory at Institute of Macromolecular Chemistry of the Academy of Sciences of the Czech Republic (IMC) in the area of polymers for biomedical applications. Particular emphasis will be given to water-soluble polymer carriers of radionuclides, thermoresponsive polymer radionuclide carriers, thermoresponsive polymers for local brachytherapy, polymer scaffolds modified with (radiolabeled) peptides and polymer copper chelators for the therapy of Wilson´s disease...
October 20, 2016: Physiological Research
Joaquim Suñer-Carbó, Antonio Boix-Montañés, Lyda Halbaut-Bellowa, Nelvis Velázquez-Carralero, Joanna Zamarbide-Ledesma, Nuria Bozal-de-Febrer, Ana Cristina Calpena-Campmany
Local delivery of imidazolic antifungals is limited by its extreme lipophilicity. Multiple emulsions (ME) are a potential vehicle to enhance the delivery of econazole nitrate (ECN), an antifungal targeted to deep-seated epidermal yeast infections. An 1% ECN hydrophilic ME was compared with a commercial formulation in terms of rheology, droplet size and in vitro antifungal activity against Candida species. Comparative in vitro drug release, human skin permeation and drug retention were investigated using vertical diffusion cells...
October 20, 2016: Mycoses
Griffin D Santarelli, Joseph K Han
Propel and Propel Mini sinus implants are mometasone furoate-coated bioabsorbable stents used as an adjunct in the management of chronic rhinosinusitis after endoscopic sinus surgery. The original sinus implant was deployed in the ethmoid sinuses to provide medialization of the middle turbinate, decrease scarring and mucosal adhesions, limit polyp regrowth, and reduce mucosal inflammation. A structurally smaller version of the Propel, the Propel Mini, was developed and now has been approved for endoscopic placement in the frontal sinuses...
October 19, 2016: Expert Opinion on Drug Delivery
Karol Kumpfer, Catia Magalhães, Jing Xie
Family evidence-based interventions (FEBIs) are effective in creating lasting improvements and preventing children's behavioral health problems, even in genetically at-risk children. Most FEBIs, however, were designed for English-speaking families. Consequently, providers have difficulty engaging non-English-speaking populations in their own country or in other countries where the content, language, and recruitment methods of the FEBIs do not reflect their culture. The practical solution has been to culturally adapt existing FEBIs...
October 18, 2016: Prevention Science: the Official Journal of the Society for Prevention Research
S K Plontke, G Götze, T Rahne, A Liebau
Local drug application to the inner ear offers a number of advantages over systemic delivery. Local drug therapy currently encompasses extracochlear administration (intratympanic injection); intracochlear administration, particularly for gene and stem cell therapy; as well as various combinations with auditory neurosensory prostheses, either evaluated in preclinical or clinical studies, or off-label. To improve rehabilitation with cochlear implants (CI), one focus is the development of drug-releasing electrode carriers, e...
October 18, 2016: HNO
S Saeidpour, S B Lohan, M Anske, M Unbehauen, E Fleige, R Haag, M C Meinke, R Bittl, C Teutloff
The skin and especially the stratum corneum (SC) act as a barrier and protect epidermal cells and thus the whole body against xenobiotica of the external environment. Topical skin treatment requires an efficient drug delivery system (DDS). Polymer-based nanocarriers represent novel transport vehicles for dermal application of drugs. In this study dendritic core-multishell (CMS) nanoparticles were investigated as promising candidates. CMS were loaded with a drug (analogue) and were applied to penetration studies of skin...
October 15, 2016: European Journal of Pharmaceutics and Biopharmaceutics
R Onnainty, E M Schenfeld, J P Petiti, M R Longhi, A Torres, M A Quevedo, G E Granero
Here, a novel drug delivery system was developed for the hydrochlorothiazide (HCT):ß-cyclodextrin (ßCD) inclusion complex loaded into chitosan (CS) nanoparticles (NPs)[CS/HCT:ßCD NPs]. It was found, for the first time, that exposure of the intestinal mucosa to free HCT resulted in an increased and abnormal intestinal permeability associated with several injuries to the intestinal epithelium. Nevertheless, the HCT delivery system obtained ameliorated the damage of the intestinal epithelium induced by HCT...
October 18, 2016: Molecular Pharmaceutics
Boriphat Methachan, Kamolrat Thanapprapasr
The emergence of theranostics with ultrasound technology is a promising development, as it opens pathways to providing more effective treatments for cancer. Advancements in ultrasound imaging would give a more detailed and accurate image for better diagnosis and treatment planning. Polymeric ultrasound contrast agents (UCAs) are appealing because they are stable and easily modified for active targeting. In addition, a better therapy could be achieved in conjunction with advancements in UCAs. The active targeting not only makes the precise imaging possible, but also leads to targeted delivery of active components to specific local treatment sites...
October 14, 2016: Ultrasound in Medicine & Biology
Vidhya Kumar, Yves Boucher, Hao Liu, Diego Ferreira, Jacob Hooker, Ciprian Catana, Andrew J Hoover, Tobias Ritter, Rakesh K Jain, Alexander R Guimaraes
PURPOSE: Losartan, an angiotensin II receptor blocker, can reduce desmoplasia and enhance drug delivery and efficacy through improving interstitial transport and vascular perfusion in pancreatic ductal adenocarcinoma (PDAC) models in mice. The purpose of this study was to determine whether magnetic resonance imaging (MRI) of magnetic iron oxide nanoparticles (MNPs) and micro-positron emission tomography (PET) measurements could respectively detect improvements in tumor vascular parameters and drug uptake in orthotopic PDAC in mice treated with losartan...
October 2016: Translational Oncology
Jenny M Pedersen, Yoo-Sik Shim, Vaibhav Hans, Martin B Phillips, Jeffrey M Macdonald, Glenn Walker, Melvin E Andersen, Harvey J Clewell, Miyoung Yoon
Accurate prediction of metabolism is a significant outstanding challenge in toxicology. The best predictions are based on experimental data from in vitro systems using primary hepatocytes. The predictivity of the primary hepatocyte-based culture systems, however, is still limited due to well-known phenotypic instability and rapid decline of metabolic competence within a few hours. Dynamic flow bioreactors for three-dimensional cell cultures are thought to be better at recapitulating tissue microenvironments and show potential to improve in vivo extrapolations of chemical or drug toxicity based on in vitro test results...
2016: Frontiers in Bioengineering and Biotechnology
Emelie Ahnfelt, Erik Sjögren, Per Hansson, Hans Lennernäs
The release rate of doxorubicin (DOX) from the drug-delivery system (DDS), DC Bead, was studied by 2 miniaturized in vitro methods: free-flowing and sample reservoir. The dependencies of the release mechanisms on in vitro system conditions were investigated experimentally and by theoretical modeling. An inverse relationship was found between release rates and bead size, most likely due to the greater total surface area. The release rates correlated positively with temperature, release medium volume, and buffer strength, although the release medium volume had larger effect than the buffer strength...
September 20, 2016: Journal of Pharmaceutical Sciences
Zhicheng Wang, Jia Nong, Robert B Shultz, Zhiling Zhang, Veronica J Tom, Ravi K Ponnappan, Yinghui Zhong
Many mechanisms contribute to the secondary injury cascades following traumatic spinal cord injury (SCI). However, most current treatment strategies only target one or a few elements in the injury cascades, and have been largely unsuccessful in clinical trials. Minocycline hydrochloride (MH) is a clinically available antibiotic and anti-inflammatory drug that has been shown to target a broad range of secondary injury mechanisms via its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. However, MH is only neuroprotective at high concentrations...
October 5, 2016: Biomaterials
Nazende Günday Türeli, Akif Emre Türeli, Marc Schneider
Design of Experiments (DoE) is a powerful tool for systematic evaluation of process parameters' effect on nanoparticle (NP) quality with minimum number of experiments. DoE was employed for optimization of ciprofloxacin loaded PLGA NPs for pulmonary delivery against Pseudomonas aeruginosa infections in cystic fibrosis (CF) lungs. Since the biofilm produced by bacteria was shown to be a complicated 3D barrier with heterogeneous meshes ranging from 100nm to 500 nm, nanoformulations small enough to travel through those channels were assigned as target quality...
October 12, 2016: International Journal of Pharmaceutics
Christopher Hernandez, Natalia Gawlik, Monika Goss, Haoyan Zhou, Selva Jeganathan, Danielle Gilbert, Agata A Exner
In situ forming implants (ISFIs) have shown promise as a sustained, local drug delivery system for therapeutics in a variety of applications.However, development of ISFIs has been hindered by poor correlation between in vitro study results and in vivo performance.In contrast to oral dosage forms, there is currently no clear consensus on a standard for in vitro drug dissolution studies for parenteral formulations. Recent studies have suggested that the disparity between in vivo and in vitro behavior of phase-inverting ISFIs may be, in part, due to differences in injection site stiffness...
October 11, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Juyoung Park, Muna Aryal, Natalia Vykhodtseva, Yong-Zhi Zhang, Nathan McDannold
Drug delivery in brain tumors is challenging because of the presence of blood-brain barrier (BBB) and the blood-tumor barrier (BTB). Focused ultrasound (FUS) combined with microbubbles can enhance the permeability of the BTB in brain tumors, as well as disrupting the BBB in the surrounding tissue. In this study, dynamic contrast-enhanced Magnetic Resonance Imaging (DCE-MRI) was used to characterize FUS-induced permeability changes in a rat glioma model and in the normal brain and to investigate the relationship between these changes and the resulting concentration of the chemotherapy agent doxorubicin (DOX)...
October 11, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Amr S Abu Lila, Masakazu Fukushima, Cheng-Long Huang, Hiromi Wada, Tatsuhiro Ishida
Pemetrexed (PMX) is a key drug for the treatment of malignant pleural mesothelioma (MPM). However, its therapeutic efficacy is cruelly restricted in many clinical settings by the over-expression of thymidylate synthase (TS) gene. Recently, we emphasized the efficacy of locally administered shRNA designed against TS gene in enhancing the cytotoxic effect of PMX against orthotopically implanted MPM cells in tumor xenograft tumor model. In the present study, we investigated the efficacy of systemic, rather than local, delivery of TS RNAi molecule in sensitizing MPM cells to the cytotoxic effect of PMX...
October 14, 2016: Molecular Pharmaceutics
Xianxian Yao, Xingxing Niu, Kexin Ma, Ping Huang, Julia Grothe, Stefan Kaskel, Yufang Zhu
A multifunctional platform is reported for synergistic therapy with controlled drug release, magnetic hyperthermia, and photothermal therapy, which is composed of graphene quantum dots (GQDs) as caps and local photothermal generators and magnetic mesoporous silica nanoparticles (MMSN) as drug carriers and magnetic thermoseeds. The structure, drug release behavior, magnetic hyperthermia capacity, photothermal effect, and synergistic therapeutic efficiency of the MMSN/GQDs nanoparticles are investigated. The results show that monodisperse MMSN/GQDs nanoparticles with the particle size of 100 nm can load doxorubicin (DOX) and trigger DOX release by low pH environment...
October 13, 2016: Small
Gowri Sivaramakrishnan, Kannan Sridharan
BACKGROUND: Local anaesthetics play a key role in reducing pain and anxiety during dental treatment. However the disadvantage of using syringe and needle technique in the maxilla, proximal to the apices of the teeth is that it is painful and also leads to collateral anaesthesia. Hence this systematic review aims to identify whether computer assisted local anaesthetic delivery system could produce predictable results similar to conventional syringe needle technique and also eliminate the disadvantages...
2016: Open Dentistry Journal
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