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Gennara Cavallaro, Carla Sardo, Emanuela Fabiola Craparo, Barbara Porsio E Gaetano Giammona
Gene therapy through the use of siRNA and a polymeric carrier are becoming an efficient therapeutic option to conventional pharmaceutical formulations for the treatment of deadly diseases, such as cancer, pulmonary, ocular and neurodegenerative diseases. However, several considerations regarding the stability, formulation, and efficacy have to be faced up until these systems could be considered to be a marketable pharmaceutical products for to extend siRNA application to clinical practice. This review is focused on the key challenges of siRNA therapeutics, with special attention on the faced obstacles and on the formulation-related difficulties, providing a list of requirements needed for obtaining an ideal carrier for siRNA...
April 14, 2017: International Journal of Pharmaceutics
Nicholas E Clay, Joseph J Whittenberg, Jiayu Leong, Vivek Kumar, Jinrong Chen, Insil Choi, Evangelos Liamas, Jeremy M Schieferstein, Jae Hyun Jeong, Dong Hyun Kim, Zhenyu Jason Zhang, Paul J A Kenis, Il Won Kim, Hyunjoon Kong
Recently, polymeric micelles self-assembled from amphiphilic polymers have been studied for various industrial and biomedical applications. This nanoparticle self-assembly typically occurs in a solvent-exchange process. In this process, the quality of the resulting particles is uncontrollably mediated by polymeric solubility and mixing conditions. Here, we hypothesized that improving the solubility of an amphiphilic polymer in an organic solvent via chemical modification while controlling the mixing rate of organic and aqueous phases would enhance control over particle morphology and size...
April 20, 2017: Nanoscale
Anna Li Volsi, Cinzia Scialabba, Valeria Vetri, Gennara Cavallaro, Mariano Licciardi, Gaetano Giammona
Folate-targeted gold nanorods (GNRs) are proposed as selective theranostic agents for osteosarcoma treatment. An amphiphilic polysaccharide based graft-copolymer (INU-LA-PEG-FA) and an amino derivative of the α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide functionalized with folic acid (PHEA-EDA-FA), have been synthesized to act as coating agents for GNRs. The obtained polymer-coated GNRs were characterized in terms of size, shape, zeta potential, chemical composition, and aqueous stability. They protected the anticancer drug nutlin-3 and were able to deliver it efficiently in different physiological media...
April 14, 2017: ACS Applied Materials & Interfaces
Gennara Cavallaro, Rossella Farra, Emanuela Fabiola Craparo, Carla Sardo, Barbara Porsio, Gaetano Giammona, Francesca Perrone, Mario Grassi, Gabriele Pozzato, Gabriele Grassi, Barbara Dapas
The limited efficacy of available treatments for hepatocellular carcinoma (HCC) requires the development of novel therapeutic approaches. We synthesized a novel cationic polymer based on α,β-poly-(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) for drug delivery to HCC cells. The copolymer was synthesized by subsequent derivatization of PHEA with diethylene triamine (DETA) and with a polyethylene glycol (PEG) derivative bearing galactose (GAL) molecules, obtaining the cationic derivative PHEA-DETA-PEG-GAL. PHEA-DETA-PEG-GAL has suitable chemical-physical characteristics for a potential systemic use and can effectively deliver a siRNA (siE2F1) targeted against the transcription factor E2F1, a gene product involved in HCC...
January 21, 2017: International Journal of Pharmaceutics
Carla Sardo, Barbara Bassi, Emanuela F Craparo, Cinzia Scialabba, Elisa Cabrini, Giacomo Dacarro, Agnese D'Agostino, Angelo Taglietti, Gaetano Giammona, Piersandro Pallavicini, Gennara Cavallaro
To overcome the low bioavailability of siRNA (small interfering RNA) and to improve their transfection efficiency, the use of non-viral delivery carriers is today a feasible approach to transform the discovery of these incredibly potent and versatile drugs into clinical practice. Polymer-modified gold nanoconstructs (AuNCs) are currently viewed as efficient and safe intracellular delivery carriers for siRNA, as they have the possibility to conjugate the ability to stably entrap and deliver siRNAs inside cells with the advantages of gold nanoparticles, which can act as theranostic agents and radiotherapy enhancers through laser-induced hyperthermia...
March 15, 2017: International Journal of Pharmaceutics
Yelin Zhu, Yan Hua, Biao Zhang, Lianhong Sun, Wenjie Li, Xin Kong, Jiong Hong
BACKGROUND: Indole pyruvic acid (IPA) is a versatile platform intermediate and building block for a number of high-value products in the pharmaceutical and food industries. It also has a wide range of applications, such as drugs for the nervous system, cosmetics, and luminophores. Chemical synthesis of IPA is a complicated and costly process. Moreover, through the biosynthesis route employing L-amino acid oxidase, the byproduct hydrogen peroxide leads the degradation of IPA. TdiD, identified as a specific tryptophan aminotransferase, could be an alternative solution for efficient IPA biosynthesis...
January 3, 2017: Microbial Cell Factories
D Triolo, E F Craparo, B Porsio, C Fiorica, G Giammona, G Cavallaro
In this paper, the potential of novel polymeric micelles as drug delivery systems for Beclomethasone Dipropionate (BDP) administration into the lung is investigated. These nanostructures are obtained starting from α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA), which was subsequently functionalized with O-(2-aminoethyl)-O'-methylpolyethylenglycole (PEG2000), ethylenediamine (EDA) and lipoic acid (LA), obtaining PHEA-PEG2000-EDA-LA graft copolymer. Empty and drug-loaded micelles possess adequate chemical-physical characteristics for pulmonary administration such as spherical shape, slightly positive surface charge and mean size of about 200nm...
March 1, 2017: Colloids and Surfaces. B, Biointerfaces
Vo Thu An Nguyen, Marie-Claire De Pauw-Gillet, Olivier Sandre, Mario Gauthier
Water-dispersible polyion complex (PIC) micelles were prepared by the self-assembly of an arborescent polystyrene-graft-poly(2-vinylpyridine) copolymer (denoted G0PS-g-P2VP or G1) serving as core and a poly(acrylic acid)-block-poly(2-hydroxyethyl acrylate) (PAA-b-PHEA) double-hydrophilic block copolymer (DHBC) forming a shell. Varying the density of hydrophilic polymer chains in the stabilizing layer provided control over the size and structure of the entities obtained, from large flocculated species to stable isolated PIC micelles with diameters ranging from 42 to 67 nm...
December 20, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
Shiqin Yu, Manuel R Plan, Gal Winter, Jens O Krömer
para-Hydroxy benzoic acid (PHBA) is the key component for preparing parabens, a common preservatives in food, drugs, and personal care products, as well as high-performance bioplastics such as liquid crystal polymers. Pseudomonas putida KT2440 was engineered to produce PHBA from glucose via the shikimate pathway intermediate chorismate. To obtain the PHBA production strain, chorismate lyase UbiC from Escherichia coli and a feedback resistant 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase encoded by gene aroG(D146N) were overexpressed individually and simultaneously...
2016: Frontiers in Bioengineering and Biotechnology
Ji Young Yoon, Keum-Jin Yang, Shi-Nae Park, Dong-Kee Kim, Jong-Duk Kim
Dexamethasone (Dex)-loaded PHEA-g-C18-Arg8 (PCA) nanoparticles (PCA/Dex) were developed for the delivery of genes to determine the synergistic effect of Dex on gene expression. The cationic PCA nanoparticles were self-assembled to create cationic micelles containing an octadecylamine (C18) core with Dex and an arginine 8 (Arg8) peptide shell for electrostatic complexation with nucleic acids (connexin 26 [Cx26] siRNA, green fluorescent protein [GFP] DNA or brain-derived neurotrophic factor [BDNF] pDNA). The PCA/Dex nanoparticles conjugated with Arg8, a cell-penetrating peptide that enhances permeability through a round window membrane in the inner ear for gene delivery, exhibited high uptake efficiency in HEI-OC1 cells...
2016: International Journal of Nanomedicine
Wei Chen, Yong Hou, Zhaoxu Tu, Lingyan Gao, Rainer Haag
pH-Degradable PVA nanogels, which are prepared by photo-crosslinking thermo-preinduced PVA nanoaggregates in water without any surfactants or toxic organic solvents, are used for intracellular PTX release and anticancer treatment. These nanogels fast degraded at mildly acidic conditions with a pH-triggered PTX release, and the degradation products are only native PVA and poly(hydroxyethyl acrylate) (PHEA) as well as acetaldehyde without any toxic byproducts. The nanogel sizes could be tailored by different temperatures during the crosslinking process...
October 31, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
José M Camacho-Zaragoza, Georgina Hernández-Chávez, Fabian Moreno-Avitia, René Ramírez-Iñiguez, Alfredo Martínez, Francisco Bolívar, Guillermo Gosset
BACKGROUND: Resveratrol is a plant natural product with many health-protecting effects which makes it an attractive chemical both for academic studies and industrial purposes. However, the low quantities naturally produced by plants as well as the unsustainable procedures of extraction, purification and concentration have prompted many biotechnological approaches to produce this chemical in large quantities from renewable sources. None of these approaches have considered a microbial coculture strategy to produce this compound...
September 29, 2016: Microbial Cell Factories
Dongqin Ding, Yongfei Liu, Yiran Xu, Ping Zheng, Haixing Li, Dawei Zhang, Jibin Sun
L-Phenylalanine (L-Phe) is an important amino acid used in both food and medicinal applications. We developed an in vitro system that allowed a direct, quantitative investigation of phenylalanine biosynthesis in E. coli. Here, the absolute concentrations of six enzymes (AroK, AroL, AroA, AroC, PheA and TyrB) involved in the shikimate (SHIK) pathway were determined by a quantitative proteomics approach and in vitro enzyme titration experiments. The reconstitution of an in vitro reaction system for these six enzymes was established and their effects on the phenylalanine production were tested...
2016: Scientific Reports
J H Chun, J M Cheon, B Y Jeong, N J Jo
We synthesized the urethane/siloxane acrylate oligomer from isophorone diisocyanate (IPDI), hydroxyl alkyl terminated polydimethylsiloxane and 2-hydroxyethyl acrylate (2-HEA). UV-curable resins were formulated from the synthesized oligomer, ethylene glycol phenyl ether acrylate (PHEA), 1,6-hexanediol diacrylate (HDDA), trimethylolpropane triacrylate (TMPTA) as a reactive diluent, 3-isocyanato-1-propene as an adhesion promoter and photoinitiators. The PET film was treated with plasma in order to introduce the functional group on the PET surface and the functional group was observed through X-ray photoelectron spectroscopy (XPS) and the Fourier transform infrared (FT-IR)...
March 2016: Journal of Nanoscience and Nanotechnology
Carlos Molina-Santiago, Baldo F Cordero, Abdelali Daddaoua, Zulema Udaondo, Javier Manzano, Miguel Valdivia, Ana Segura, Juan-Luis Ramos, Estrella Duque
Aromatic compounds such as L-phenylalanine, 2-phenylethanol and trans-cinnamate are aromatic compounds of industrial interest. Current trends support replacement of chemical synthesis of these compounds by 'green' alternatives produced in microbial cell factories. The solvent tolerant Pseudomonas putida DOT-T1E strain was genetically modified to produce up to 1 g l-1 of L-phenylalanine. In order to engineer this strain, the following stepwise process was carried out: 1) we selected random mutants that are resistant to toxic phenylalanine analogs; 2) we then deleted up to five genes belonging to phenylalanine metabolism pathways, which greatly diminished the internal metabolism of phenylalanine; 3) in these mutants, we overexpressed the pheAfbr gene, which encodes a recombinant variant of PheA that is insensitive to feed-back inhibition by phenylalanine...
July 14, 2016: Microbiology
E F Craparo, S Di Gioia, A Trapani, S Cellamare, G Belgiovine, D Mandracchia, G Giammona, G Cavallaro, M Conese
In this study, novel polymeric nanoparticles (NPs) were developed and their potential as carriers for beclomethasone dipropionate (BDP) into the lung after aerosolization was demonstrated by in vivo studies in mice. In particular, these NPs were obtained starting from two polyaspartamide-based copolymers which were synthesized by chemical reaction of α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) and its pegylated derivative (PHEA-PEG2000) with poly(lactic acid) (PLA). To obtain nanosized particles, the high pressure homogenization (HPH)-solvent evaporation method was followed by using an organic phase containing both PHEA-PLA and PHEA-PEG2000-PLA (at a weight ratio equal to 1:1), lactose as cryoprotectant and no surfactant was adopted...
August 20, 2016: International Journal of Pharmaceutics
Maria José Valera, Albert Mas, Wolfgang R Streit, Estibaliz Mateo
BACKGROUND: We report on the functional screening and identification of an active quorum quenching (QQ) gene in the Komagataeibacter europaeus strain CECT 8546, which is a member of the acetic acid bacteria (AAB). RESULTS: Using a previously published screening protocol (Schipper et al., in Appl Environ Microbiol 75:224-233, 2009. doi: 10.1128/AEM.01389-08 ) for QQ genes, we identified a single gene, designated gqqA, that interfered strongly with bacterial quorum sensing (QS) in various reporter strains...
May 24, 2016: Microbial Cell Factories
Panoraia I Siafaka, Asimina P Zisi, Maria K Exindari, Ioannis D Karantas, Dimitrios N Bikiaris
Absorbable and non-absorbable dressings have been fabricated into sponges via a modified thermally induced phase separation method, using a grafted derivative of chitosan with 2-hydroxyethylacrylate (CS-g-PHEA). The material was synthesized via free-radical polymerization and was characterized with FT-IR and (1)H NMR spectroscopies. The swelling ability, biocompatibility and biodegradability of the dressings were evaluated through in vitro assays while antibacterial studies were performed using three different bacterial strains, Methicillin susceptible Staphylococcus aureus (MSSA), Methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa...
June 5, 2016: Carbohydrate Polymers
Suzanne M Kosina, Megan A Danielewicz, Mujahid Mohammed, Jayashree Ray, Yumi Suh, Suzan Yilmaz, Anup K Singh, Adam P Arkin, Adam M Deutschbauer, Trent R Northen
Synthetic microbial ecology has the potential to enhance the productivity and resiliency of biotechnology processes compared to approaches using single isolates. Engineering microbial consortia is challenging; however, one approach that has attracted significant attention is the creation of synthetic obligate mutualism using auxotrophic mutants that depend on each other for exchange or cross-feeding of metabolites. Here, we describe the integration of mutant library fitness profiling with mass spectrometry based exometabolomics as a method for constructing synthetic mutualism based on cross-feeding...
July 15, 2016: ACS Synthetic Biology
Tammy J Bullwinkle, Michael Ibba
Gene expression relies on quality control for accurate transmission of genetic information. One mechanism that prevents amino acid misincorporation errors during translation is editing of misacylated tRNAs by aminoacyl-tRNA synthetases. In the absence of editing, growth is limited upon exposure to excess noncognate amino acid substrates and other stresses, but whether these physiological effects result solely from mistranslation remains unclear. To explore if translation quality control influences cellular processes other than protein synthesis, an Escherichia coli strain defective in Tyr-tRNA(Phe) editing was used...
February 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
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