Delivery systems made of natural-origin polymers for tissue engineering and regenerative medicine applications

There is an emergent need in the development of more specific and effective therapeutic agent carriers to help on the regeneration of a plethora of tissues. The ultimate aim of bioactive factors delivery systems development is to improve the human health with the fewest possible adverse reactions. While there have been many polymeric scaffolds and matrices with different forms and compositions developed to load and deliver bioactive factors, the delivery strategy should be established based on the type of molecules to deliver and mechanisms to control their release. As most bioactive factors such as proteins and genes are water-soluble, natural polymers are more favored than synthetic ones for this purpose. A core-shell structuring of biomaterials (in the cases of particles or fibers) where water-based polymers being placed in the inner core part may be the most common design principal to secure bioactive factors during the processing of synthetic drug delivery scaffolds.(undefined)info:eu-repo/semantics/submittedVersio

Tuberculosis chemotherapy: current drug delivery approaches

Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance

Investigation of temperature sensitivity behaviors of water soluble polyacrylamides

Temperature sensitive polymers with a lower critical solution temperature (LCST) are used in a variety of industries such as the pharmaceutical, cosmetic, food, and paint. These polymers are generally of the poly(N-alkylacrylamide) type, of which poly(N-isopropylacrylamide) (PNIPA) is the most commonly used. More novel poly(N-alkylacrylamide)s have also been the subject of much attention recently. In this study, N-alkylacrylamides containing different alkyl groups were synthesized by nucleophylic substitution reactions of various amines with acryloyl chloride. They were polymerized using the solution polymerization method, and the temperature sensitivities of the polymers were investigated. For this purpose, three monomers, N,N-diethylacrylamide, N-cyclopropylacrylamide, and 4-piperidineethanolacrylamide, were synthesized using diethylamine, cyclopropylamine, and 4-piperidineethanol, as the amines, respectively. The obtained polymers, poly(N,N-diethylacrylamide) (PDEA), poly(N- cyclopropylacrylamide) (PCPA), and poly(4-piperidineethanolacrylamide) (PPEA), were found to be thermoresponsive, particularly PPEA is a potential novel material that can be utilized as an alternative to the common temperature sensitive polymers. The effects of several conditions on the LCST and the critical flocculation temperature (CFT) of the polymers were also investigated. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013 Copyright © 2012 Wiley Periodicals, Inc

chromium(VI) ions

The polyethyleneglycolmethacrylate-co-vinylimidazole (PEGMA-VI) copolymers, that can be used in heavy metal removal applications, were synthesized and characterized; and their use as sorbents in heavy metal removal was investigated. It was determined that the ligand vinylimidazole was successfully inserted into the polymer structure. Then, chromium (Cr(VI)) and nickel (Ni(II)) ions were used as model species to investigate the usability of the obtained microspheres in heavy metal removal. The effects of pH of the adsorption medium, initial concentration of the metal ions and VI content of PEGMA-VI microspheres were investigated as the effective parameters on the adsorption capacities of the microspheres. The adsorption rate of the microspheres was also investigated for determination of the optimum adsorption time which is the required time for maximum adsorption capacity. The adsorption capacities under optimum conditions were also determined. The order of adsorption affinities of PEGMA-VI microspheres with respect to the used metals was determined by competitive adsorption studies. According to the obtained results, the highest adsorption affinity of the PEGMA-VI microspheres was towards Cr(VI) ions, the adsorption affinity was less for Ni(II) and the least affinity was towards Cu(II) ions. The adsorption-desorption studies showed that the microspheres were reusable without a significant decrease in the ion adsorption capacities. (C) 2009 Elsevier B.V. All rights reserved

Chondrogenesis of human mesenchymal stem cells by microRNA loaded triple polysaccharide nanoparticle system

WOS: 000472241700072PubMed ID: 31147048Degenerative cartilage is the pathology of severe depletion of extracellular matrix components in articular cartilage. In diseases like osteoarthritis, misregulation of microRNAs contributes the pathology and collectively leads to disruption of the homeostasis. In this study chondroitin sulfate/hyaluronic acid/chitosan nanoparticles were prepared and successfully characterized chemically and morphologically. Results demonstrated higher chondroitin sulfate amounts led smaller nanoparticles, but lower surface zeta potential due to high electronegativity. After optimization of chondroitin sulfate amounts regarding size and charge, nanoparticles were loaded with microRNA-149-5p, a therapeutic miRNA downregulated in osteoarthritis, and evaluated focusing on their loading efficiency, release behaviour, cytotoxicity and gene transfection efficiency in vitro. Results showed all nanoparticle formulations were non-toxic and promising gene delivery agents, due to increased levels of microRNA-149-5p and decreased mRNA levels of microRNA's target, FUT-1. Highest gene transfection efficiency was obtained with the nanoparticle formulation which had the highest chondroitin sulfate load and smallest size. In addition, owing to their high chondroitin sulfate cargo, all nanoparticles were reported to enhance chondrogenesis, which was demonstrated by gene expression analysis and sulfated glycosaminoglycan (sGAG) staining. The obtained data suggest that the delivery of microRNA-149-5p via polysaccharide based carriers could achieve collaborative impact in cartilage regeneration and have a potential to enhance osteoarthritis treatment

EFFECTS OF ABCE1 DOWN-REGULATION BY RNAi ON CHEMOSENSITIVITY OF LUNG CANCER CELLS

WOS: 000343139500383

Downregulation of ABCE1 via siRNA affects the sensitivity of A549 cells against chemotherapeutic agents

WOS: 000351474100017PubMed: 25744244ATP-binding cassette E1 (ABCE1) is involved in several biological functions in cancer cells such as tumor proliferation, antiapoptotic pathway and chemoresistance mechanism. This work aimed to investigate the alterations in chemosensitivity of A549 lung cancer cells for 5-Fluorouracil (5-FU) and irinotecan by silencing ABCE1 using specific small interfering RNAs (siRNA). The cells were treated with low doses of drugs, alone and also their combinations with ABCE1 siRNA. Cytotoxicity, cell proliferation and apoptosis/necrosis evaluations were performed in order to examine the effects of the combined treatment. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to confirm the downregulation of ABCE1. We also investigated the levels of B cell lymphoma 2 (Bcl-2) and mammalian target of rapamycin (mTOR) after the treatments by RT-PCR. Downregulation of ABCE1 improved the anticancer effects of 5-FU in inducing cell viability/proliferation inhibition and apoptosis/necrosis, whereas interestingly, almost did not change or slightly reduced the anticancer effects of irinotecan. ABCE1 expression significantly decreased by transfecting the cells with ABCE1 siRNA. Moreover, Bcl-2 and mTOR levels changed after the single or combined therapy in parallel with the apoptotic and antiproliferation effect. In conclusion, the simultaneous treatment of lung cancer cells with ABCE1 siRNA and 5-FU exhibited synergistic or additive effects; however, ABCE1 siRNA and irinotecan had unexpected antagonistic effects. Our findings demonstrate that the strategy of downregulation of ABCE1 may be included in conventional 5-FU chemotherapy for lung cancer, minimizing the usage of 5-FU at high dosages.Hacettepe University, Scientific Research Projects Coordination UnitHacettepe University [968]This work was financially supported by Hacettepe University, Scientific Research Projects Coordination Unit (Grant No. 968)

The effect of calcium chloride concentration on alginate/Fmoc-diphenylalanine hydrogel networks

Bayram, Cem/0000-0001-8717-4668; CELIK, EKIN/0000-0003-1966-3907WOS: 000377737000027PubMed: 27207058Peptide based hydrogels gained a vast interest in the tissue engineering studies thanks to great superiorities such as biocompatibility, supramolecular organization without any need of additional crosslinker, injectability and tunable nature. Fmoc-diphenylalanine (FmocFF) is one of the earliest and widely used example of these small molecule gelators that have been utilized in biomedical studies. However, Fmoc-peptides are not feasible for long term use due to low stability and weak mechanical properties at neutral pH. In this study, Fmoc-FF dipeptides were mechanically enhanced by incorporation of alginate, a biocompatible and absorbable polysaccharide. The binary hydrogel is obtained via molecular self-assembly of FmocFF dipeptide in alginate solution followed by ionic crosslinldng of alginate moieties with varying concentrations of calcium chloride. Hydrogel characterization was evaluated in terms of morphology, viscoelastic moduli and diffusional phenomena and the structures were tested as 3D scaffolds for bovine chondrocytes. In vitro evaluation of scaffolds lasted up to 14 days and cell viability, sulphated glycosaminoglycan (sGAG) levels, collagen type II synthesis were determined. Our results showed that alginate incorporation into FmocFF hydrogels leads to better mechanical properties and higher stability with good biocompatibility. (C) 2016 Elsevier B.V. All rights reserved.Hacettepe University Scientific Research Projects Coordination Office (HU-BAP) [1136]This study was supported by the Hacettepe University Scientific Research Projects Coordination Office (HU-BAP, project no: 1136)