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Delivery models

Steven K Jones, Kirk Douglas, Anthony F Shields, Olivia M Merkel
Using an orthotopic model of ovarian cancer, we studied the delivery of siRNA in nanoparticles of tri-block copolymers consisting of hyperbranched polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol) (hyPEI-g-PCL-b-PEG) with and without a folic acid targeting ligand. A SKOV-3/LUC FRα overexpressing cell line was employed to mimic the clinical manifestations of ovarian cancer. Both targeted and non-targeted micelleplexes were able to effectively deliver siRNA to the primary tumor and its metastases, as measured by gamma scintillation counting and confocal microscopy...
June 13, 2018: Biomaterials
Zhi Li, Junya Zhang, Xiao Li, Xinhong Guo, Zhenzhong Zhang
The Fe3O4@C @NaYF4:Yb,Er nano-carriers with multifunctional were synthesized. The mitoxantrone (MTO) were selected as model drug and these nanoparticles have high drug loading (0.63mg/mg). The temperature of Fe3O4@C @NaYF4:Yb,Er in water approached 60°C with 808nm irritation(2.5W/cm2). The cumulative release of these nano drug carriers significantly increased because of temperature increasing, and the 4T1 cells growth inhibition rates were 59.15%, almost 2.25-fold higher than MTO group (p<0.05). Since the nanoparticles had auto-fluorescence under 808nm irritation, the nano-carries could be traced both in vitro and in vivo studies...
June 20, 2018: Journal of Pharmaceutical Sciences
Antonio Lopalco, Nunzio Denora
This chapter presents an outline of the recent available information regarding safety, toxicity, and efficacy of nano drug delivery systems. Of particular importance is the evaluation of several key factors to design nontoxic and effective nanoformulations. Among them, we focus on nanostructure materials and synthesis methods, mechanisms of interactions with biological systems, treatment of nanoparticles, manufacture impurities, and nanostability. Emphasis is given to in silico, in vitro, and in vivo models used to assess and predict the toxicity of these new formulations...
2018: Methods in Molecular Biology
Miguel Montenegro-Nicolini, Patricio E Reyes, Miguel O Jara, Parameswara R Vuddanda, Andrónico Neira-Carrillo, Nicole Butto, Sitaram Velaga, Javier O Morales
The buccal mucosa appears as a promissory route for biologic drug administration, and pharmaceutical films are flexible dosage forms that can be used in the buccal mucosa as drug delivery systems for either a local or systemic effect. Recently, thin films have been used as printing substrates to manufacture these dosage forms by inkjet printing. As such, it is necessary to investigate the effects of printing biologics on films as substrates in terms of their physical and mucoadhesive properties. Here, we explored solvent casting as a conventional method with two biocompatible polymers, hydroxypropyl methylcellulose, and chitosan, and we used electrospinning process as an electrospun film fabrication of polycaprolactone fibers due to its potential to elicit mucoadhesion...
June 22, 2018: AAPS PharmSciTech
Aisha Janjua, Tracy Roberts, Nicola Okeahialam, T Justin Clark
OBJECTIVE: To determine the cost-effectiveness of Gynaecology Teaching Associate (GTA) teaching versus conventional pelvic model (manikin) teaching of pelvic examination skills for final year medical students within a UK undergraduate obstetrics and gynaecology (O&G) curriculum. METHODS: An economic evaluation was carried out alongside a randomised controlled trial involving 492 final year medical students. 240 students received manikin teaching, and 241 GTA-led teaching...
June 22, 2018: BMJ Open
Anjan K Pradhan, Praveen Bhoopathi, Sarmistha Talukdar, Xue-Ning Shen, Luni Emdad, Swadesh K Das, Devanand Sarkar, Paul B Fisher
Prostate cancer (PC) is a principal cause of cancer-associated morbidity in men. Although 5-year survival of patients with localized PC approaches 100 percent, survival decreases precipitously after metastasis. Bone is the preferred site for disseminated PC cell colonization, altering the equilibrium of bone homeostasis resulting in weak and fragile bones. Currently, no curative options are available for PC bone metastasis. MDA-7/IL-24 is a well-studied cytokine established as a therapeutic in a wide-array of cancers upon delivery as a gene therapy...
June 22, 2018: Molecular Cancer Therapeutics
Li Dai, Yue Chen, Wen Sun, Shiliang Liu
OBJECTIVE: To assess whether hypertensive disorders during pregnancy (HDPs) are associated with the subsequent development of end-stage renal disease (ESRD). METHODS: The present study included 1 598 043 women who delivered in Canadian hospitals between April 1993 and March 2003. The baseline information was from the Canadian Institute for Health Information's Discharge Abstract Database. Women with chronic kidney disease, diabetes mellitus, and other specific conditions were excluded...
June 19, 2018: Journal of Obstetrics and Gynaecology Canada: JOGC, Journal D'obstétrique et Gynécologie du Canada: JOGC
Raymond U Osarogiagbon
The goal of this article is to provide an overview of the state of the evidence for, and challenges to, sustainable implementation of multidisciplinary thoracic oncology programs. Multidisciplinary care is much advocated by professional groups and makers of clinical guidelines, but little practiced. The gap between universal recommendation and scant evidence of practice suggests the existence of major barriers to program implementation. We examine 2 articles published in this issue of Clinical Lung Cancer to illustrate problems with the evidence base for multidisciplinary care...
July 2018: Clinical Lung Cancer
Amy Egolf, Pamela Hoffman, Megan M Mroczkowski, Laura M Prager, John W Tyson, Kathleen Donise
Pediatric psychiatric emergency care is delivered in different settings with vastly different resources around the country. Training programs lack guidance on developing optimal curricula for this highly variable but crucial setting. A model curriculum for child and adolescent psychiatry trainees may be helpful to provide such guidance; its components include recommendations for assessing baseline knowledge, identifying and teaching core subject content, encouraging development of essential skills, and building in supervision for learners...
July 2018: Child and Adolescent Psychiatric Clinics of North America
Katieli da Silva Souza Campanholi, Gustavo Braga, Jéssica Bassi da Silva, Nicola Leone da Rocha, Lizziane Maria Belloto de Francisco, Évelin Lemos de Oliveira, Marcos Luciano Bruschi, Lidiane Hoshino, Francielle Sato, Noboru Hioka, Wilker Caetano
Photodynamic therapy (PDT) is a therapeutic modality that has shown effectiveness in the inactivation of cancer cell lines and microorganisms. Treatment consists of activating the photosensitizer (PS) upon light irradiation of adequate wavelength. After reaching the excited state, the PS can handle the inter-system conversion through energy transfer to the molecular oxygen, generating reactive oxygen species. This especially applies to singlet oxygen (1O2), which is responsible for the selective destruction of the sick tissue...
June 22, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Victor Carrer, Beatriz Guzmán, Meritxell Martí, Cristina Alonso, Luisa Coderch
BACKGROUND: The major in vitro permeation studies are currently performed in Franz-type diffusion cells because of their simplicity, cost effectiveness and because the experimental conditions can be easily controlled. Apart from the skin, Franz-type diffusion cells can be used with synthetic membranes. Nevertheless, they do not emulate the nature of the lipidic matrix, which is responsible for the topical barrier function. OBJECTIVE: This paper offers two new approaches combining different synthetic membranes (Strat-M&reg; and Nucleopore&reg; ) with lanolin, which provides lipidic components similar to the lipidic matrix...
June 21, 2018: Pharmaceutics
Aimee Mooney, Naomi Beale, Melanie Fried-Oken
Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by insidious language deterioration. This young-onset disorder leaves adults with reduced communication skills for participation in social activities. There is limited evidence regarding group treatment for individuals with PPA, though the principles of chronic aphasia groups can be applied to this clinical population. We developed a PPA group treatment model incorporating compensatory strategies from augmentative and alternative communication (AAC), communication partner training from aphasia rehabilitation, and systematic instruction from dementia management...
July 2018: Seminars in Speech and Language
Asima Farooq, Ali Shukur, Cai Astley, Lubomira Tosheva, Peter Kelly, Debra Whitehead, May Azzawi
Blood vessel disease is a major contributor to cardiovascular morbidity and mortality and is hallmarked by dysfunction of the lining endothelial cells (ECs). These cells play a significant role in vascular homeostasis, through the release of mediators to control vessel diameter, hence tissue perfusion. Mesoporous silica nanoparticles (MSNs) can be used as potential drug delivery platforms for vasodilator drugs. Here, using an ex vivo model of vascular function, we examine the use of titania coating for improved biocompatibility and release dynamics of MSN loaded sodium nitroprusside (SNP)...
June 19, 2018: Acta Biomaterialia
M Shimoji, B Ramaswamy, M I Shukoor, P Benhal, A Broda, S Kulkarni, P Malik, B McCaffrey, J-F Lafond, A Nacev, I N Weinberg, B Shapiro, D A Depireux
This paper investigates the safety of a novel 'magnetic injection' method of delivering therapy to the cochlea, in a rodent model. In this method of administration, a magnetic field is employed to actively transport drug-eluting iron oxide-core nanoparticles into the cochlea, where they then release their drug payload (we delivered the steroid prednisolone). Our study design and selection of control groups was based on published regulatory guidance for safety studies that involve local drug delivery. We tested for both single and multiple delivery doses to the cochlea, and found that magnetic delivery did not harm hearing...
June 19, 2018: European Journal of Pharmaceutical Sciences
Beibei Hu, Wei Sun, Haiting Li, Helin Sui, Sanming Li
Thermogels, used as multi-functional drug-loading materials, have properties that mainly rely on their gelator structure. Although a large variety of organogel systems are used as drug delivery carriers, relatively few have been investigated in terms of their structure-property correlations based on amino acid derivative gelators. Here, a series of amino acid based gelators were synthesized to explore the role of the gelator structure on functional properties, with the aim of establishing a connection between the molecular parameters and gel properties...
June 19, 2018: International Journal of Pharmaceutics
Vimala N Bharadwaj, Rachel K Rowe, Jordan Harrison, Chen Wu, Trent R Anderson, Jonathan Lifshitz, P David Adelson, Vikram D Kodibagkar, Sarah E Stabenfeldt
Clinically, traumatic brain injury (TBI) results in complex heterogeneous pathology that cannot be recapitulated in single pre-clinical animal model. Therefore, we focused on evaluating utility of nanoparticle (NP)-based therapeutics following three diffuse-TBI models: mild-closed-head injury (mCHI), repetitive-mCHI and midline-fluid percussion injury (FPI). We hypothesized that NP accumulation after diffuse TBI correlates directly with blood-brain-barrier permeability. Mice received PEGylated-NP cocktail (20-500nm) (intravenously) after single- or repetitive-(1 impact/day, 5 consecutive days) CHI (immediately) and midline-FPI (1h, 3h and 6h)...
June 19, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Hriday Bera, Sanoj Kumar, Sabyasachi Maiti
Olive oil-entrapped diethanolamine-modified high-methoxyl pectin (DMP)-gellan gum (GG)-bionanofiller composites were developed for controlled intragastric delivery of metformin HCl (MFM). DMP had a degree of amidation of 48.7% and was characterized further by FTIR, XRD and DSC analyses. MFM-loaded composites were subsequently accomplished by green synthesis via ionotropic gelation technique using zinc acetate as cross-linker. The thermal, X-ray and infrared analyses suggested an environment in the composites compatible with the drug, except certain degree of attenuation in drug's crystallinity...
June 19, 2018: International Journal of Biological Macromolecules
Xiaotian Zhao, Yun Qian, Yuan Cheng, Xiaoshuang Guo, Wei-En Yuan
Non-viral vector gene delivery is generally limited by its potential toxicity problems, poor transfection abilities, serum stability, or relatively complex construction processes of modified polyplexes. Thus, we develop an efficient and stable polyplex system through convenient construction methods. Here, polyethyleneimine (PEI) 1.8 kDa and glutaraldehyde (GA) are used to construct a novel twice-condensed pDNA polyplex system using a one-pot construction method, including pH-responsive C[double bond, length as m-dash]N linkages by which different PEI molecules on one single polyplex can link with each other...
June 22, 2018: Biomaterials Science
Nur Izyani Kamaruzman, Snigdha Tiash, Maeirah Ashaie, Ezharul Hoque Chowdhury
Breast cancer, the second leading cause of female deaths worldwide, is usually treated with cytotoxic drugs, accompanied by adverse side-effects, development of chemoresistance and relapse of disease condition. Survival and proliferation of the cancer cells are greatly empowered by over-expression or over-activation of growth factor receptors and anti-apoptotic factors. Identification of these key players that cross-talk to each other, and subsequently, knockdown with their respective siRNAs in a synchronous manner could be a promising approach to precisely treat the cancer...
June 22, 2018: Biomedicines
V E Klenov, S L Boulet, R B Mejia, D M Kissin, E Munch, A Mancuso, B J Van Voorhis
OBJECTIVE: To compare live birth rates (LBRs) and multiple birth rates (MBRs) between elective single-embryo transfer (eSET) and double-embryo transfer (DET) in donor oocyte in vitro fertilization (IVF) treatments in both a cycle-level and clinic-level analysis. METHODS: Donor oocyte IVF treatments performed by US IVF clinics reporting to the Centers for Disease Control and Prevention in 2013-2014 were included in the analysis. Primary outcomes included LBR and MBR...
June 21, 2018: Journal of Assisted Reproduction and Genetics
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