Browsing by Subject "ORAL DELIVERY"

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  • Sabouri, Salehe; Sepehrizadeh, Zargham; Amirpour-Rostami, Sahar; Skurnik, Mikael (2017)
    Phage therapy is an old method of combating bacterial pathogens that has recently been taken into consideration due to the alarming spread of antibiotic resistance. Escherichia coli 0157:H7 is a foodborne pathogen that causes hemorrhagic colitis and life-threatening Hemolytic Uremic Syndrome (HUS). There are several studies on isolation of specific phages against E. coli 0157:H7 and more than 60 specific phase have been published so far. Although in vitro experiments have been successful in elimination or reduction of E. coli 0157:H7numbers, in vivo experiments have not been as promising. This may be due to escape of bacteria to locations where phages have difficulties to enter or due to the adverse conditions in the gastrointestinal tract that affect phage viability and proliferation. To get around the latter obstacle, an alternative phage delivery method such as polymer microen-capsulation should be tried. While the present time results are not very encouraging the work should be continued as more efficient phage treatment regimens might be found in future. (C)2016 Elsevier B.V. All rights reserved.
  • Khan, Daulat Haleem; Bashir, Sajid; Khan, Muhammad Imran; Figueiredo, Patricia; Santos, Hélder A.; Peltonen, Leena (2020)
    The aim of the present study was to prepare niosomal formulations for dual drug therapy of ceftriaxone sodium and poorly water-soluble rifampicin by the ecological probe sonication method. Pluronic L121 and Span 60 were used as surface active agents and the optimization of the composition was made with the aid of Design of Experiment (DoE) concept. Concentration levels of charge inducing agent, dicetylphosphate (DCP), and Pluronic L121 were studied as variables. Prepared niosomes with varying concentrations of DCP and Pluronic L121 resulted in small sized niosomes with sizes ranging from 165 nm to 893 nm. During the four weeks stability testing, the particle sizes of the empty niosomes were reduced, while the particle sizes of the drug loaded niosomes were increased very slightly. The optimized formulations resulted in stable niosomes with high drug entrapment efficiencies: entrapment efficiency was 99% for rifampicin and 96% for ceftriaxone. All the niosomal formulations showed faster in vitro drug release rates as compared to bulk drug formulations. In conclusion, ceftriaxone and rifampicin loaded niosomes prepared with Pluronic L121 and Span 60 resulted in stable, small sized niosomes with high drug entrapment efficiencies and improved drug release profiles.
  • Fontana, Flavia; Martins, Joao P.; Torrieri, Giulia; Santos, Helder A. (2019)
    Nanotechnology holds the promise of bringing revolutionary therapeutic strategies into the clinic. However, an enormous fraction of the currently proposed nanotechnology-based therapies suffers from lack of reproducibility, complexity, high costs, and scale-up-related issues. For these reasons, the research community is moving toward the miniaturization of biomaterials and fabrication methods. Customizable microfluidic-based products have gained tremendous relevance in the development of biomedical technologies. This review provides an overview of different materials that can be used for the fabrication of microfluidic devices, as well as the other parameters influencing the production of biomaterials and biosensors. Moreover, several advanced microfluidic-based technologies that are designed to overcome the current challenges of cancer, immunotherapy, and diabetes therapy, among others are described. Then, the pros and cons of microfluidics as alternative to conventional preparation methods, and the challenges of translating this technique to an industrial context are highlighted. Overall, microfluidic technologies and their accessibility to the research community offer a set of exciting opportunities to bridge the development of innovative therapies and their commercialization in the foreseeable future.
  • Mutso, Margit; Nikonov, Andrei; Pihlak, Arno; Zusinaite, Eva; Viru, Liane; Selyutina, Anastasia; Reintamm, Tonu; Kelve, Merike; Saarma, Mart; Karelson, Mati; Merits, Andres (2015)
    The inhibitory potency of an antisense oligonucleotide depends critically on its design and the accessibility of its target site. Here, we used an RNA interference-guided approach to select antisense oligonucleotide target sites in the coding region of the highly structured hepatitis C virus (HCV) RNA genome. We modified the conventional design of an antisense oligonucleotide containing locked nucleic acid (LNA) residues at its termini (LNA/DNA gapmer) by inserting 8-oxo-2'-deoxyguanosine (8-oxo-dG) residues into the central DNA region. Obtained compounds, designed with the aim to analyze the effects of 8-oxo-dG modifications on the antisense oligonucleotides, displayed a unique set of properties. Compared to conventional LNA/DNA gapmers, the melting temperatures of the duplexes formed by modified LNA/DNA gapmers and DNA or RNA targets were reduced by approximately 1.6-3.3 degrees C per modification. Comparative transfection studies showed that small interfering RNA was the most potent HCV RNA replication inhibitor (effective concentration 50 (EC50) : 0.13 nM), whereas isosequential standard and modified LNA/DNA gapmers were approximately 50-fold less efficient (EC50 : 5.5 and 7.1 nM, respectively). However, the presence of 8-oxo-dG residues led to a more complete suppression of HCV replication in transfected cells. These modifications did not affect the efficiency of RNase H cleavage of antisense oligonucleotide: RNA duplexes but did alter specificity, triggering the appearance of multiple cleavage products. Moreover, the incorporation of 8-oxo-dG residues increased the stability of antisense oligonucleotides of different configurations in human serum.
  • Haider, Malik Salman; Luebtow, Michael M.; Endres, Sebastian; Forster, Stefan; Flegler, Vanessa J.; Boettcher, Bettina; Aseyev, Vladimir; Pöppler, Ann-Christin; Luxenhofer, Robert (2020)
    Polymeric micelles are typically characterized as core-shell structures. The hydrophobic core is considered as a depot for hydrophobic molecules, and the corona-forming block acts as a stabilizing and solubilizing interface between the core and aqueous milieu. Tremendous efforts have been made to tune the hydrophobic block to increase the drug loading and stability of micelles, whereas the role of hydrophilic blocks is rarely investigated in this context, with poly(ethylene glycol) (PEG) being the gold standard of hydrophilic polymers. To better understand the role of the hydrophilic corona, a small library of structurally similar A-B-A-type amphiphiles based on poly(2-oxazoline)s and poly(2-oxazine)s is investigated by varying the hydrophilic block A utilizing poly(2-methyl-2-oxazoline) (pMeOx; A) or poly(2-ethyl-2-oxazoline) (pEtOx; A*). In terms of hydrophilicity, both polymers closely resemble PEG. The more hydrophobic block B bears either a poly(2-oxazoline) and poly(2-oxazine) backbone with C3 (propyl) and C4 (butyl) side chains. Surprisingly, major differences in loading capacities from A-B-A > A*-B-A > A*-B-A* is observed for the formulation with two poorly water-soluble compounds, curcumin and paclitaxel, highlighting the importance of the hydrophilic corona of polymer micelles used for drug formulation. The formulations are also characterized by various nuclear magnetic resonance spectroscopy methods, dynamic light scattering, cryogenic transmission electron microscopy, and (micro) differential scanning calorimetry. Our findings suggest that the interaction between the hydrophilic block and the guest molecule should be considered an important, but previously largely ignored, factor for the rational design of polymeric micelles.