Hybrid inorganic-organic capsules for efficient intracellular delivery of novel siRNAs against influenza A (H1N1) virus infection

This work was supported by ARUK project grant 21210 ‘Sustained and Controllable Local Delivery of Anti-inflammatory Therapeutics with Nanoengineered Microcapsules’. The work was also supported in part by Russian Foundation of Basic Research grants No. 16-33-50153 mol_nr, No. 16-33-00966 mol_a, Russian Science Foundation grant No. 15-15-00170 and Russian Governmental Program ‘‘Nauka’’, No. 1.1658.2016, 4002

Edible bio-based nanostructures: delivery, absorption and potential toxicity

The development of bio-based nanostructures as nanocarriers of bioactive compounds to specific body sites has been presented as a hot topic in food, pharmaceutical and nanotechnology fields. Food and pharmaceutical industries seek to explore the huge potential of these nanostructures, once they can be entirely composed of biocompatible and non-toxic materials. At the same time, they allow the incorporation of lipophilic and hydrophilic bioactive compounds protecting them against degradation, maintaining its active and functional performance. Nevertheless, the physicochemical properties of such structures (e.g., size and charge) could change significantly their behavior in the gastrointestinal (GI) tract. The main challenges in the development of these nanostructures are the proper characterization and understanding of the processes occurring at their surface, when in contact with living systems. This is crucial to understand their delivery and absorption behavior as well as to recognize potential toxicological effects. This review will provide an insight into the recent innovations and challenges in the field of delivery via GI tract using bio-based nanostructures. Also, an overview of the approaches followed to ensure an effective deliver (e.g., avoiding physiological barriers) and to enhance stability and absorptive intestinal uptake of bioactive compounds will be provided. Information about nanostructures potential toxicity and a concise description of the in vitro and in vivo toxicity studies will also be given.Joana T. Martins, Oscar L. Ramos, Ana C. Pinheiro, Ana I. Bourbon, Helder D. Silva and Miguel A. Cerqueira (SFRH/BPD/89992/2012, SFRH/BPD/80766/2011, SFRH/BPD/101181/2014, SFRH/BD/73178/2010, SFRH/BD/81288/2011, and SFRH/BPD/72753/2010, respectively) are the recipients of a fellowship from the Fundacao para a Ciencia e Tecnologia (FCT, POPH-QREN and FSE, Portugal). The authors thank the FCT Strategic Project PEst-OE/EQB/LA0023/2013 and the project "BioInd-Biotechnology and Bioengineering for improved Industrial and Agro-Food processes," REF.NORTE-07-0124-FEDER-000028, co-funded by the Programa Operacional Regional do Norte (ON.2-O Novo Norte), QREN, FEDER. We also thank to the European Commission: BIOCAPS (316265, FP7/REGPOT-2012-2013.1) and Xunta de Galicia: Agrupamento INBIOMED (2012/273) and Grupo con potencial de crecimiento. The support of EU Cost Action FA1001 is gratefully acknowledged

A synergic approach to enhance long-term culture and manipulation of MiaPaCa-2 pancreatic cancer spheroids

Tumour spheroids have the potential to be used as preclinical chemo-sensitivity assays. However, the production of three-dimensional (3D) tumour spheroids remains challenging as not all tumour cell lines form spheroids with regular morphologies and spheroid transfer often induces disaggregation. In the field of pancreatic cancer, the MiaPaCa-2 cell line is an interesting model for research but it is known for its difficulty to form stable spheroids; also, when formed, spheroids from this cell line are weak and arduous to manage and to harvest for further analyses such as multiple staining and imaging. In this work, we compared different methods (i.e. hanging drop, round-bottom wells and Matrigel embedding, each of them with or without methylcellulose in the media) to evaluate which one allowed to better overpass these limitations. Morphometric analysis indicated that hanging drop in presence of methylcellulose leaded to well-organized spheroids; interestingly, quantitative PCR (qPCR) analysis reflected the morphometric characterization, indicating that same spheroids expressed the highest values of CD44, VIMENTIN, TGF-β1 and Ki-67. In addition, we investigated the generation of MiaPaCa-2 spheroids when cultured on substrates of different hydrophobicity, in order to minimize the area in contact with the culture media and to further improve spheroid formation

ECONOMIES WITH PUBLIC PROJECTS: EFFICIENCY AND DECENTRALIZATION

The article deals with the two fundamental theorems of welfare economics for production economies with a finite set of agents, infinitely many private goods, and a set of public projects. The problem of efficiency and decentralization is addressed under the following very general assumptions: (a) the commodity-price duality is endowed with a consistent locally convex topology; (b) the set of public projects is without any mathematical structure. Moreover, any agent is characterized by a nonordered preference relation depending on consumption goods and public projects. Approximate and exact welfare theorems are discussed throughout the article. Copyright 2007 by the Economics Department Of The University Of Pennsylvania And Osaka University Institute Of Social And Economic Research Association.

Plasma assisted immobilization of microcapsules for drug delivery on collagen-based matrices for peripheral nerve regeneration

The aim of this work was the superficial activation, by means of plasma treatments, of crosslinked collagen-based scaffolds for nerve regeneration, in order to immobilize anionic and cationic microcapsules (MCPs) for drug delivery. Matrices with axially oriented pores have the potential to improve the regeneration of peripheral nerves and spinal cord by physically supporting and guiding the growth of neural structures across the site of injury. To improve mechanical resistance and stability in water solutions, it is necessary to crosslink collagenous fibres by formation of amide bonds with consequent reduction of free amino and carboxylic groups useful for immobilization approach of drug delivery systems like MCPs. Plasma chemical processes represent a successful approach because allow polar groups to be grafted on the surface, without modifying the massive properties of the bulk. Plasma surface modification was performed in a capacitively-coupled rf (13.56 MHz) glass reactor fed with different precursors like N2, H2O, C2H4 to study the effect of plasma parameters on the chemical properties of the resulting material and its ability to improve the immobilization of polyelectrolyte MCPs. Cylindrical scaffolds were synthesized by freeze-drying technique and dehydrothermally crosslinked. Polyelectrolyte capsules were obtained by LbL method. Scaffolds were characterized by means of WCA and XPS. Fluorescence microscopy was used to verify MCPs immobilization. After treatments, scaffolds became hydrophilic and able to absorb water. The success of grafting, on the external surface and within the scaffold core, was clearly revealed. The obtained results demonstrate that plasma processing of cross-linked collagen allows to enhance MCPs immobilization and that, by changing the typology of functional groups on the plasma treated surfaces, a different attitude to immobilize negatively or positively charged MCPs is observed

Collagen-based matrices with axially oriented pores activated via plasma and decorated with polyelectrolyte microcapsules for drug delivery

Introduction Collagen matrices with properly designed porous structure have the potential to improve the regeneration of tissues like peripheral nerves, by physically supporting and guiding the growth of tissue structures across the site of injury [1]. Due to the formation of amide bonds during cross-linking of the scaffold, an abatement of groups naturally present on the collagen chains (e.g. NH2, COOH) occurs. Such groups are generally used as anchor moieties for biomolecules or drug delivery systems like microcapsules (MCPs) [2]. In this work, cylindrical collagen-based scaffolds with axially oriented pores, useful for peripheral nerve regeneration, were prepared and then subjected to plasma processing [3], with the aim of grafting polar groups on them. Materials and methods Synthesis of scaffolds- Collagen-based scaffolds with axially oriented pores were synthesized from an aqueous suspension of Type I collagen (3 wt%, Semed S, Kensey Nash Corp.) and dehydrothermally crosslinked, as described in the literature [1]. Synthesis of MCPs- Anionic and cationic capsules, carrying FITC- and RITC-labeled dextrans into the cavities, respectively, were obtained using the LbL method [2]. Plasma processes- performed at 13.56 MHz radio frequency (rf) were fed with N2 and H2O vapors by changing the gas feed composition. The total gas flow was maintained at 15 sccm, at 150 mTorr and 30 W with variable treatment time. Results and discussion Plasma treatments imparted immediate hydrophilicity and ability to absorb water to the scaffolds. For comparison, it should be noted that untreated crosslinked collagen scaffolds did not absorb water. Plasma treatments were able to effectively change the chemical characteristics of both the external and internal surface of the scaffolds. After MCPs immobilization, fluorescence microscopy clearly demonstrated that: surfaces functionalized by means of NH2 groups are able to support the immobilization of negatively charged MCPs; COOH plasma functionalized materials are able to support positively charged ones. Conclusions This paper demonstrates that plasma processing of cross-linked collagen is a powerful tool to enhance MCPs immobilization. Acknowledgments The Italian Regional project PON 02 00563 3448479 RINOVATIS for funding