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Drug Delivery and Translational Research

Xiaoxuan Liu, Lin Zhu, Jingjing Ma, Xinxiao Qiao, Dunwan Zhu, Lanxia Liu, Xigang Leng
RNA interference (RNAi) is among the most potential approach for the therapy of hepatocellular carcinoma and the major barrier hindering siRNA therapeutics is the low efficiency of delivery to the desired cells. The current study aimed at developing a novel peptide for more efficient hepatoma targeted siRNA delivery, by combining luteinizing hormone-releasing hormone with hepatoma targeting specificity and MPG(△NLS) with cytoplasm-delivery tendency. The developed bifunctional peptide LHRH-MPG(△NLS) and siRNA were mixed together and resulted in LHRH-MPG(△NLS)/siRNA polyplexes through self-assembly...
November 28, 2016: Drug Delivery and Translational Research
Saeed Shojaee, Ali Nokhodchi, Mohammed Maniruzzaman
Hydrophilic matrix systems are currently some of the most widely used drug delivery systems for controlled-release oral dosage forms. Amongst a variety of polymers, polyethylene oxide (PEO) is considered an important material used in pharmaceutical formulations. As PEO is sensitive to thermal oxidation, it is susceptible to free radical oxidative attack. The aim of this study was to investigate the stability of PEO based formulations containing different model drugs with different water solubility, namely propranolol HCl, theophylline and zonisamide...
November 21, 2016: Drug Delivery and Translational Research
Emilia Sawicki, Remy B Verheijen, Alwin D R Huitema, Olaf van Tellingen, Jan H M Schellens, Bastiaan Nuijen, Jos H Beijnen, Neeltje Steeghs
Elacridar is an inhibitor of the permeability glycoprotein (P-gp) and the breast cancer resistance protein (BCRP) and is a promising absorption enhancer of drugs that are substrates of these drug-efflux transporters. However, elacridar is practically insoluble in water, resulting in low bioavailability which currently limits its clinical application. We evaluated the in vitro dissolution and clinical pharmacokinetics of a novel amorphous solid dispersion (ASD) tablet containing elacridar. The dissolution from ASD tablets was compared to that from a crystalline powder mixture in a USP type II dissolution apparatus...
November 18, 2016: Drug Delivery and Translational Research
Kamal Dua, Nicole G Hansbro, Paul S Foster, Philip M Hansbro
The rapid advancement in the area of microRNAs (miRNAs) from discovery to their translation into therapeutic moieties reflects their significance as important regulators in the management of disease pathology. The miRNAs can potentially be a new class of drugs in the near future for the treatment of various lung diseases, but it lacks the current knowledge how these identified therapeutic moieties can be designed into an effective, patient complaint and targeted drug delivery system. miRNAs have characteristic features like small size and low molecular weight which makes them easily translated into an effective drug delivery system...
November 15, 2016: Drug Delivery and Translational Research
Amit Kumar Chaudhary, Ram I Mahato
The completion of human genome project, decrease in the sequencing cost, and correlation of genome sequencing data with specific diseases led to the exponential rise in the nucleic acid-based therapeutic approaches. In the third annual Biopharmaceutical Research and Development Symposium (BRDS) held at the Center for Drug Discovery and Lozier Center for Pharmacy Sciences and Education at the University of Nebraska Medical Center (UNMC), we highlighted the remarkable features of the nucleic acid-based nanomedicines, their significance, NIH funding opportunities on nanomedicines and gene therapy research, challenges and opportunities in the clinical translation of nucleic acids into therapeutics, and the role of intellectual property (IP) in drug discovery and development...
November 15, 2016: Drug Delivery and Translational Research
Manisha Pandey, Najwa Mohamad, Wan-Li Low, Claire Martin, Mohd Cairul Iqbal Mohd Amin
Burn wound management is a complex process because the damage may extend as far as the dermis which has an acknowledged slow rate of regeneration. This study investigates the feasibility of using hydrogel microparticles composed of bacterial cellulose and polyacrylamide as a dressing material for coverage of partial-thickness burn wounds. The microparticulate carrier structure and surface morphology were investigated by Fourier transform infrared, X-ray diffraction, elemental analysis, and scanning electron microscopy...
November 4, 2016: Drug Delivery and Translational Research
Zhenbao Li, Wenjuan Zhang, Yan Gao, Rongwu Xiang, Yan Liu, Mingming Hu, Mei Zhou, Xiaohong Liu, Yongjun Wang, Zhonggui He, Yinghua Sun, Jin Sun
Valsartan, an angiotensin II receptor antagonist, is widely used to treat high blood pressure in the clinical setting. However, its poor water solubility results in the low oral bioavailability. The aim of this study was to improve dissolution rate and oral bioavailability by developing a self-nanoemulsifying drug delivery system. Saturation solubility of valsartan in various oils, surfactants, and cosurfactants was investigated, and the optimized formulation was determined by central composite design-response surface methodology...
November 3, 2016: Drug Delivery and Translational Research
Marion Jamard, Todd Hoare, Heather Sheardown
While eye drops account for the majority of ophthalmic formulation for drug delivery, their efficiency is limited by rapid pre-corneal loss. In this study, we investigate nanogel suspensions in order to improve the topical ocular therapy by reducing dosage and frequency of administration. We synthesized self-assembling nanogels of 140 nm by grafting side chains of poly(N-tert-butylacrylamide) (PNtBAm) on methylcellulose via cerium ammonium nitrate. Successful grafting of PNtBAm onto methylcellulose (MC) was confirmed by both NMR and ATR...
November 2, 2016: Drug Delivery and Translational Research
Vibhuti Agrahari, Abhirup Mandal, Vivek Agrahari, Hoang M Trinh, Mary Joseph, Animikh Ray, Hicheme Hadji, Ranjana Mitra, Dhananjay Pal, Ashim K Mitra
The eye is a distinctive organ with protective anatomy and physiology. Several pharmacokinetics compartment models of ocular drug delivery have been developed for describing the absorption, distribution, and elimination of ocular drugs in the eye. Determining pharmacokinetics parameters in ocular tissues is a major challenge because of the complex anatomy and dynamic physiological barrier of the eye. In this review, pharmacokinetics of these compartments exploring different drugs, delivery systems, and routes of administration is discussed including factors affecting intraocular bioavailability...
October 31, 2016: Drug Delivery and Translational Research
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
Ilva D Rupenthal, Michael O'Rourke
No abstract text is available yet for this article.
October 20, 2016: Drug Delivery and Translational Research
Carolin Thiele, Brigitta Loretz, Claus-Michael Lehr
Regioselective oxidation of water-soluble starch and conversion with alkyl diamines resulted in defined cationic starch derivatives. Those were assessed in their potential for polyplex formation, biocompatibility, and transfection efficacy. The new polymers have the advantage of being biodegradable, being not cytotoxic at rather high concentrations (LC50 > 400 μg/ml) for C2 substitution, and reach transfection efficiencies comparable to commercial transfection reagents. The polymer with the highest transfection efficacy is a C12 substituted polymer (degree of substitution = 30 %) at N/P 3...
October 3, 2016: Drug Delivery and Translational Research
Venkata Ramana Malipeddi, Rajendra Awasthi, Daniela Dal Molim Ghisleni, Marina de Souza Braga, Irene Satiko Kikuchi, Terezinha de Jesus Andreoli Pinto, Kamal Dua
The present study aimed to develop matrix-type transdermal drug delivery system (TDDS) of metoprolol tartrate using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA). The transdermal films were evaluated for physical parameters, Fourier transform infrared spectroscopy analysis (FTIR), differential scanning calorimetry (DSC), in vitro drug release, in vitro skin permeability, skin irritation test and stability studies. The films were found to be tough, non-sticky, easily moldable and possess good tensile strength...
September 27, 2016: Drug Delivery and Translational Research
Paul D Gavin, Mahmoud El-Tamimy, Hooi Hong Keah, Ben J Boyd
Transdermal drug delivery is a useful route of administration that avoids first-pass metabolism and more invasive delivery options. However, many drugs require enhancers to enable sufficient drug absorption to reach therapeutic effect. Alpha-tocopheryl phosphate (TP) and di-alpha-tocopheryl phosphate (T2P) are two phosphorylated forms of vitamin E which form tocopheryl phosphate mixture (TPM) when combined, and have been proposed to enhance the dermal and transdermal delivery of actives of interest. Here, we report the physicochemical characteristics and morphological properties of TPM formulations, including particle size, deformability and morphology, and its ability to facilitate the transport of carnosine, vitamin D3, CoEnzyme Q10 and caffeine into, and across, the skin...
September 26, 2016: Drug Delivery and Translational Research
George R Dakwar, Kevin Braeckmans, Wim Ceelen, Stefaan C De Smedt, Katrien Remaut
Delivery of small interfering RNA (siRNA) is recently gaining tremendous attention for the treatment of ovarian cancer. The present study investigated the potential of different liposomal formulations composed of (2,3-dioleoyloxy-propyl)-trimethylammonium (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) encapsulating siRNA (hydration method) for their ability to knockdown luciferase (Luc) activity in human ovarian cancer SKOV-3 cells. Fluorescence single particle tracking (fSPT) and fluorescence correlation spectroscopy (FCS) in human-undiluted ascites fluid obtained from a peritoneal carcinomatosis patient revealed that cationic hydra-lipoplexes (HYDRA-LPXs) and HYDRA-LPXs decorated with stable DSPE-PEG (DSPE HYDRA-LPXs) showed high stability during at least 24 h...
September 8, 2016: Drug Delivery and Translational Research
Ummara Butt, Amr ElShaer, Lori A S Snyder, Athina Chaidemenou, Raid G Alany
Fatty acids (FAs) are used by many organisms as defence mechanism against virulent bacteria. The high safety profile and broad spectrum of activity make them potential alternatives to currently used topical antibiotics for the treatment of eye infections in neonates. The current study utilised a Design of Experiment approach to optimise the quantification of five fatty acids namely; lauric acid, tridecanoic acid, myristoleic acid, palmitoleic acid and α-linolenic acid. The significance of the influence of the experimental parameters such as volume of catalyst, volume of n-hexane, incubation temperature, incubation time and the number of extraction steps on derivatisation was established by statistical screening with a factorial approach...
December 2016: Drug Delivery and Translational Research
Raghu Raj Singh Thakur, Ismaiel A Tekko, Farhan Al-Shammari, Ahlam A Ali, Helen McCarthy, Ryan F Donnelly
In this study, dissolving microneedles (MNs) were used to enhance ocular drug delivery of macromolecules. MNs were fabricated using polyvinylpyrrolidone (PVP) polymer of various molecular weights (MWs) containing three model molecules of increasing MW, namely fluorescein sodium and fluorescein isothiocyanate-dextrans (with MW of 70 k and 150 k Da). Arrays (3 × 3) of PVP MNs with conical shape measuring about 800 μm in height with a 300 μm base diameter, containing the model drugs, were fabricated and characterized for their fracture forces, insertion forces (in the sclera and cornea), depth of penetration (using OCT and confocal imaging), dissolution time and in vitro permeation...
December 2016: Drug Delivery and Translational Research
Seppo Rönkkö, Kati-Sisko Vellonen, Kristiina Järvinen, Elisa Toropainen, Arto Urtti
In vivo toxicity and absorption studies of topical ocular drugs are problematic, because these studies involve invasive tissue sampling and toxic effects in animal models. Therefore, different human corneal models ranging from simple monolayer cultures to three-dimensional models have been developed for toxicological prediction with in vitro models. Each system has its own set of advantages and disadvantages. Use of non-corneal cells, inadequate characterization of gene-expression profiles, and accumulation of genomic aberrations in human corneal models are typical drawbacks that decrease their reliability and predictive power...
December 2016: Drug Delivery and Translational Research
Kevin D Lance, Daniel A Bernards, Natalie A Ciaccio, Samuel D Good, Thaís S Mendes, Max Kudisch, Elliot Chan, Mynna Ishikiriyama, Robert B Bhisitkul, Tejal A Desai
Current administration of ranibizumab and other therapeutic macromolecules to the vitreous and retina carries ocular risks, a high patient treatment burden, and compliance barriers that can lead to suboptimal treatment. Here we introduce a device that produces sustained release of ranibizumab in the vitreous cavity over the course of several months. Composed of twin nanoporous polymer thin films surrounding a ranibizumab reservoir, these devices provide release of ranibizumab over 16 weeks in vitro and 12 weeks in vivo, without exhausting the initial drug payload...
December 2016: Drug Delivery and Translational Research
Seong-Jin Kim, Ju-Hyung Shin, Jin-Yong Noh, Chang-Seon Song, Yeu-Chun Kim
This study focused on the development of novel coating formulations for stainless steel microneedles against influenza A virus. With in vitro studies, various viscosity enhancers and stabilizers were screened based on the hemagglutination activity of the vaccine, which was coated and dried onto a stainless steel chip at room temperature for 1 day. Following the long-term storage test, the hemagglutination activity and particle size of the vaccine, which was formulated with conventional or methylcellulose or hydroxyethyl cellulose and dried onto the microneedle, were monitored...
October 2016: Drug Delivery and Translational Research
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