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Drug delivery

Jeannine Coburn, Jamie Harris, Alexander D Zakharov, Jennifer Poirier, Naohiko Ikegaki, Andre Kajdacsy-Balla, Monika Pilichowska, Alexander V Lyubimov, Hiroyuki Shimada, David L Kaplan, Bill Chiu
Neuroblastoma is the most common extracranial childhood solid tumor. Treatment of high risk tumors require intense multi-cycle chemotherapies, resulting in short- and long-term toxicities. Here we present treatment of an orthotopic neuroblastoma mouse model, with silk fibroin materials loaded with vincristine, doxorubicin, or the combination as a intratumoral, sustained release system. The materials, loaded with vincristine with or without doxorubicin, significantly decreased neuroblastoma tumor growth compared to materials loaded without drug or doxorubicin only as well as intravenous (IV) drug treatment...
October 22, 2016: International Journal of Cancer. Journal International du Cancer
Lauren E Marshall, Roy Koomullil, Andra R Frost, Joel L Berry
A preclinical testing model for cancer therapeutics that replicates in vivo physiology is needed to accurately describe drug delivery and efficacy prior to clinical trials. To develop an in vitro model of breast cancer that mimics in vivo drug/nutrient delivery as well as physiological size and bio-composition, it is essential to describe the mass transport quantitatively. The objective of the present study was to develop in vitro and computational models to measure mass transport from a perfusion system into a 3D extracellular matrix (ECM)...
October 21, 2016: Annals of Biomedical Engineering
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
Adenike Okunlola, Amusa Sarafadeen Adebayo, Moji Christianah Adeyeye
Tropical starches from Dioscorea dumetorum (bitter) and Dioscorea oppositifolia (Chinese) yams were acetylated with acetic anhydride in pyridine medium and utilized as polymers for the delivery of repaglinide in microsphere formulations in comparison to ethyl cellulose. Acetylated starches of bitter and Chinese yams with degrees of substitution of 2.56 and 2.70 respectively were obtained. Acetylation was confirmed by FTIR, (1)H NMR spectroscopy. A 3(2) factorial experimental design was performed using polymer type and drug-polymer ratio as independent variables...
October 18, 2016: International Journal of Biological Macromolecules
Phei Er Saw, Jinho Park, Sangyong Jon, Omid C Farokhzad
A major problem with cancer chemotherapy begins when cells acquire resistance. Drug-resistant cancer cells typically upregulate multi-drug resistance proteins such as P-glycoprotein (P-gp). However, the lack of overexpressed surface biomarkers has limited the targeted therapy of drug-resistant cancers. Here we report a drug-delivery carrier decorated with a targeting ligand for a surface marker protein Extra-domain B(EDB) specific to drug-resistant breast cancer cells as a new therapeutic option for the aggressive cancers...
October 18, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Vivienne H Tam, Chris Sosa, Rui Liu, Nan Yao, Rodney D Priestley
The blood brain barrier (BBB) is a major obstacle to drug delivery for diseases of the central nervous system (CNS). This brief review highlights the current invasive and non-invasive technologies available to address this problem. In particular, nanomedicine has shown much promise as a non-invasive strategy due to its drug loading capabilities, ease of targeting to the BBB, and small size. The versatility of this technology in terms of type of drug and imaging agent, carrier material, and targeting mechanism is highlighted in this review...
October 18, 2016: International Journal of Pharmaceutics
Rajani Shah
BACKGROUND: Child delivery in a health facility is important to reduce maternal mortality. Bypassing nearby birthing facility to deliver at a hospital is common in developing countries including Nepal. Very little is known about the extent and determinants of bypassing the birthing centres in Nepal. This study measures the status of bypassing, characteristics of bypassers and their reasons for bypassing. METHODS: A community-based cross-sectional study was carried out in six rural village development committees of Chitwan district of Nepal...
October 21, 2016: BMC Health Services Research
Si-Yong Qin, Ai-Qing Zhang, Si-Xue Cheng, Lei Rong, Xian-Zheng Zhang
Carrier-assistant drug delivery systems (DDSs) have been rapidly established for cancer therapy and great strides have been made in recent years. However, further development of DDSs is retarded by the aspects such as the low drug carrying capacity, carrier-induced toxicity and immunogenicity, complex synthesis manipulation. Drug self-delivery systems (DSDSs), in which active drugs exhibit nanoscale characteristic to realize intracellular delivery by themselves without the help of nanocarriers, have been rapidly developed to address these issues...
October 13, 2016: Biomaterials
Cong Wu, Meng-Qing Gong, Bo-Ya Liu, Ren-Xi Zhuo, Si-Xue Cheng
To effectively reverse multiple drug resistance (MDR) in tumor treatments, a functional nano-sized drug delivery system with active targeting function and pH sensitivity was prepared for the co-delivery of multiple drug resistance inhibitors. Buthionine sulfoximine (BSO) to inhibit GSH synthesis and celecoxib (CXB) to down-regulate P-gp expression were co-loaded in polymer/inorganic hybrid nanoparticles to form buthionine sulfoximine/celecoxib@biotin-heparin/heparin/calcium carbonate/calcium phosphate nanoparticles (BSO/CXB@BNP)...
October 13, 2016: Colloids and Surfaces. B, Biointerfaces
Aaron S Kesselheim, Wesley Eddings, Tara Raj, Eric G Campbell, Jessica M Franklin, Kathryn M Ross, Lisa A Fulchino, Jerry Avorn, Joshua J Gagne
BACKGROUND: Generic drugs are cost-effective versions of brand-name drugs approved by the Food and Drug Administration (FDA) following proof of pharmaceutical equivalence and bioequivalence. Generic drugs are widely prescribed by physicians, although there is disagreement over the clinical comparability of generic drugs to brand-name drugs within the physician community. The objective of this survey was to assess physicians' perceptions of generic drugs and the generic drug approval process...
2016: PloS One
Boris Redko, Helena Tuchinsky, Tamar Segal, Dror Tobi, Galia Luboshits, Osnat Ashur-Fabian, Albert Pinhasov, Gabi Gerlitz, Gary Gellerman
The newly discovered short (9 amino acid) non-RGD S-S bridged cyclic peptide ALOS-4 (H-cycl(Cys-Ser-Ser-Ala-Gly-Ser-Leu-Phe-Cys)-OH), which binds to integrin αvβ3 is investigated as peptide carrier for targeted drug delivery against human metastatic melanoma. ALOS4 binds specifically the αvβ3 overexpressing human metastatic melanoma WM-266-4 cell line both in vitro and in ex vivo assays. Coupling ALOS4 to the topoisomerase I inhibitor Camptothecin (ALOS4-CPT) increases the cytotoxicity of CPT against human metastatic melanoma cells while reduces dramatically the cytotoxicity against non-cancerous cells as measured by the levels of γH2A...
October 19, 2016: Oncotarget
Alexander N Zelikin, Carsten Ehrhardt, Anne Marie Healy
Biological drugs generated via recombinant techniques are uniquely positioned due to their high potency and high selectivity of action. The major drawback of this class of therapeutics, however, is their poor stability upon oral administration and during subsequent circulation. As a result, biological drugs have very low bioavailability and short therapeutic half-lives. Fortunately, tools of chemistry and biotechnology have been developed into an elaborate arsenal, which can be applied to improve the pharmacokinetics of biological drugs...
October 21, 2016: Nature Chemistry
Thidarat Wongpinyochit, Blair F Johnston, F Philipp Seib
Silk is a promising biopolymer for biomedical and pharmaceutical applications due to its outstanding mechanical properties, biocompatibility and biodegradability, as well its ability to protect and subsequently release its payload in response to a trigger. While silk can be formulated into various material formats, silk nanoparticles are emerging as promising drug delivery systems. Therefore, this article covers the procedures for reverse engineering silk cocoons to yield a regenerated silk solution that can be used to generate stable silk nanoparticles...
October 8, 2016: Journal of Visualized Experiments: JoVE
Po C Liu, Yi T Lee, Chun Y Wang, Ya-Tang Yang
We describe a low cost, configurable morbidostat for characterizing the evolutionary pathway of antibiotic resistance. The morbidostat is a bacterial culture device that continuously monitors bacterial growth and dynamically adjusts the drug concentration to constantly challenge the bacteria as they evolve to acquire drug resistance. The device features a working volume of ~10 ml and is fully automated and equipped with optical density measurement and micro-pumps for medium and drug delivery. To validate the platform, we measured the stepwise acquisition of trimethoprim resistance in Escherichia coli MG 1655, and integrated the device with a multiplexed microfluidic platform to investigate cell morphology and antibiotic susceptibility...
September 27, 2016: Journal of Visualized Experiments: JoVE
Lisa A Sawicki, April M Kloxin
Click chemistries have been investigated for use in numerous biomaterials applications, including drug delivery, tissue engineering, and cell culture. In particular, light-mediated click reactions, such as photoinitiated thiol-ene and thiol-yne reactions, afford spatiotemporal control over material properties and allow the design of systems with a high degree of user-directed property control. Fabrication and modification of hydrogel-based biomaterials using the precision afforded by light and the versatility offered by these thiol-X photoclick chemistries are of growing interest, particularly for the culture of cells within well-defined, biomimetic microenvironments...
September 29, 2016: Journal of Visualized Experiments: JoVE
Frantz Le Dévédec, Loujin Houdaihed, Christine Allen
In this study, an amphiphilic copolymer that includes a core-forming block with phenyl groups was synthesized by living anionic polymerization of phenyl glycidyl ether (PheGE) on methoxy-polyethylene glycol (mPEG-b-PPheGE). Characterization of the copolymer revealed a narrow molecular distribution (PDI < 1.03) and confirmed the degree of polymerization of mPEG122-b-(PheGE)15. The critical micelle concentration of the copolymer was evaluated using an established fluorescence method with the aggregation behavior evaluated by dynamic light scattering and transmission electronic microscopy...
October 10, 2016: Journal of Visualized Experiments: JoVE
Emanuele Mauri, Alessandro Sacchetti, Filippo Rossi
The use of polymers as biomaterials has provided significant advantages in therapeutic applications. In particular, the possibility to modify and functionalize polymer chains with compounds that are able to improve biocompatibility, mechanical properties, or cell viability allows the design of novel materials to meet new challenges in the biomedical field. With the polymer functionalization strategies, click chemistry is a powerful tool to improve cell-compatibility and drug delivery properties of polymeric devices...
October 7, 2016: Journal of Visualized Experiments: JoVE
Ali Kermanizadeh, Klaus Villadsen, Ragnhild G Østrem, Knud J Jensen, Peter Møller, Steffen Loft
Utilisation of functionalized liposomes as the means of targeted delivery of therapeutics may enhance specific transport of biologically active drugs to target tissues, while avoiding or reducing undesired side effects. In the present investigation, peptide-conjugated cationic liposomes were constructed with the aim of targeting integrins (i.e. vitronectin and/or fibronectin receptors) on activated endothelial cells. The peptide-conjugated liposomes induced only cytotoxicity at the highest concentration in non-activated or activated endothelial cells, as well as in co-culture of endothelial cells and macrophages...
October 21, 2016: Basic & Clinical Pharmacology & Toxicology
Maria Elisabeth Moreira, Ana Paula Esteves Pereira, Saint Clair Gomes Junior, Ruth Guinsburg, Maria Fernanda Branco de Almeida, Silvana Granado Gama, Maria do Carmo Leal
BACKGROUND: Approximately 5-10 % of newborns require some form of resuscitationupon delivery; several factors, such as maternal abnormal conditions, gestational age and type of delivery could be responsible for this trend. This study aimed to describe the factors associated with the need for positive pressure ventilation (PPV) via a mask or endotracheal tube and the use of supplemental O2 in newborns with a gestational age greater than 34 weeks in Brazil. METHODS: We performed a cross-sectional study and obtained data from the Birth in Brazil Survey...
October 17, 2016: Reproductive Health
I Bravo-Osuna, V Andrés-Guerrero, P Pastoriza Abal, I T Molina-Martínez, R Herrero-Vanrell
Efficient treatment of ocular diseases can be achieved thanks to the proper use of ophthalmic formulations based on emerging pharmaceutical approaches. Among them, microtechnology and nanotechnology strategies are of great interest in the development of novel drug delivery systems to be used for ocular therapy. The location of the target site in the eye as well as the ophthalmic disease will determine the route of administration (topical, intraocular, periocular, and suprachoroidal administration) and the most adequate device...
October 20, 2016: Drug Delivery and Translational Research
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