Chitosan/carrageenan nanoparticles: effect of cross-linking with tripolyphosphate

Chitosan/carrageenan/tripolyphosphate nanoparticles were prepared by polyelectrolyte complexation/ionic gelation, the latter compound acting as cross-linker. The incorporation of the three components in the nanoparticle matrix was assessed by analytical techniques (FTIR, XPS and TOF-SIMS). Using chitosan/carrageenan nanoparticles as control, the effect of the cross-linker in the particles properties was studied. A decrease in size (from 450-500 nm to 150-300 nm) and in zeta potential (from +75 - +85 mV to +50 - +60 mV), and an increase in production yield (from 15-20% to 25-35%), and in stability (from one week to up to 9 months) were observed. Also, a correlation between positive to negative charge ratios in the formulations and the above characteristics was established. The small size and high positive surface charge make the developed chitosan/carrageenan/tripolyphosphate nanoparticles potential tools for an application in mucosal delivery of macromolecules

Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy

The pulmonary delivery of antitubercular drugs is a promising approach to treat lung tuberculosis. This strategy not only allows targeting the infected organ instantly, it can also reduce the systemic adverse effects of the antibiotics. In light of that, this work aimed at producing fucoidan-based inhalable microparticles that are able to associate a combination of two first-line antitubercular drugs in a single formulation. Fucoidan is a polysaccharide composed of chemical units that have been reported to be specifically recognised by alveolar macrophages (the hosts of Mycobacterium). Inhalable fucoidan microparticles were successfully produced, effectively associating isoniazid (97%) and rifabutin (95%) simultaneously. Furthermore, the produced microparticles presented adequate aerodynamic properties for pulmonary delivery with potential to reach the respiratory zone, with a mass median aerodynamic diameter (MMAD) between 3.6-3.9 mu m. The formulation evidenced no cytotoxic effects on lung epithelial cells (A549), although mild toxicity was observed on macrophage-differentiated THP-1 cells at the highest tested concentration (1 mg/mL). Fucoidan microparticles also exhibited a propensity to be captured by macrophages in a dose-dependent manner, as well as an ability to activate the target cells. Furthermore, drug-loaded microparticles effectively inhibited mycobacterial growth in vitro. Thus, the produced fucoidan microparticles are considered to hold potential as pulmonary delivery systems for the treatment of tuberculosis.Portuguese Foundation for Science and Technology [PTDC/DTP-FTO/0094/2012, UID/Multi/04326/2013, UID/BIM/04773/2013]; CAPES-Brazil [BEX 1168/13-4

Inhalable spray-dried chondroitin sulphate microparticles: effect of different solvents on particle properties and drug activity

Spray-drying stands as one of the most used techniques to produce inhalable microparticles, but several parameters from both the process and the used materials affect the properties of the resulting microparticles. In this work, we describe the production of drug-loaded chondroitin sulphate microparticles by spray-drying, testing the effect of using different solvents during the process. Full characterisation of the polymer and of the aerodynamic properties of the obtained microparticles are provided envisaging an application in inhalable tuberculosis therapy. The spray-dried microparticles successfully associated two first-line antitubercular drugs (isoniazid and rifabutin) with satisfactory production yield (up to 85%) and drug association efficiency (60%-95%). Ethanol and HCl were tested as co-solvents to aid the solubilisation of rifabutin and microparticles produced with the former generally revealed the best features, presenting a better ability to sustainably release rifabutin. Moreover, these presented aerodynamic properties compatible with deep lung deposition, with an aerodynamic diameter around 4 μm and fine particle fraction of approximately 44%. Finally, it was further demonstrated that the antitubercular activity of the drugs remained unchanged after encapsulation independently of the used solvent.UID/Multi/04326/2019; SFRH/BD/52426/2013; ED481B 2018/071info:eu-repo/semantics/publishedVersio

Inhalable antitubercular therapy mediated by locust bean gum microparticles

Tuberculosis remains a major global health problem and alternative therapeutic approaches are needed. Considering the high prevalence of lung tuberculosis (80% of cases), the pulmonary delivery of antitubercular drugs in a carrier system capable of reaching the alveoli, being recognised and phagocytosed by alveolar macrophages (mycobacterium hosts), would be a significant improvement to current oral drug regimens. Locust bean gum (LBG) is a polysaccharide composed of galactose and mannose residues, which may favour specific recognition by macrophages and potentiate phagocytosis. LBG microparticles produced by spray-drying are reported herein for the first time, incorporating either isoniazid or rifabutin, first-line antitubercular drugs (association efficiencies >82%). Microparticles have adequate theoretical properties for deep lung delivery (aerodynamic diameters between 1.15 and 1.67 μm). The cytotoxic evaluation in lung epithelial cells (A549 cells) and macrophages (THP-1 cells) revealed a toxic effect from rifabutin-loaded microparticles at the highest concentrations, but we may consider that these were very high comparing with in vivo conditions. LBG microparticles further evidenced strong ability to be captured by macrophages (percentage of phagocytosis >94%). Overall, the obtained data indicated the potential of the proposed system for tuberculosis therapy

Recovery of platinum(IV) and palladium(II) from complex hydrochloric acid matrices by a thiodiglycolamide derivative

The solvent extraction performance of N,N’-dimethyl-N,N’-dicyclohexylthiodiglycolamide (DMDCHTDGA) towards Pt(IV) and Pd(II) in HCl solutions has recently been published. It was shown that these two platinum-group metals (PGMs) are efficiently extracted from 8 M HCl aqueous phases, being subsequently separated by sequential strippings: 1 M HCl allows Pt(IV) recovery, whereas Pd(II) is only back-extracted by thiourea in HCl. In this work, selectivity tests were carried out to evaluate the performance of DMDCHTDGA towards the recovery of both PGMs, from 8 M HCl aqueous phases, when in presence of Rh(III), Fe(III), Ni(II), Zn(II), Al(III), Ce(III) and Zr(IV), simulating the leaching solutions that may result from the hydrometallurgical treatment of spent automobile catalytic converters. It was generally observed that the additional metal ions do not affect the recovery of Pd(II) and Pt(IV) by DMDCHTDGA. Fe(III), Zn(II) and Zr(IV) are co-extracted with Pt(IV) and Pd(II); Fe(III) and Zn(II) were efficiently scrubbed with water, whereas Zr(IV) was removed by an acidified aqueous solution. Inversely, Ni(II) is not extracted, and Rh(III) and Ce(III) appear only traceably in the loaded organic phase. Al(III) is a concern, as it is appreciably extracted, and none of the tested backextraction solutions was able to strip it

A nanoparticle comprising a micelle formed by an amphiphilic block copolymer and encapsulating a gadolinium complex

Publication number: WO2011/113616The present invention relates to a nanoparticle comprising a micelle formed by an amphophilic block-copolymer and an agent encapsulated within said micelle. The present invention also relates to a composition comprising such nanoparticle and to the use of such nanoparticle and/or of such composition. More particularly, in one embodiment, the invention describes a new class of polymeric nanoparticles as smart Tl contrast agent for MR imaging for breast cancer early detection. These nanoparticles contrast agents have the capability to remain switched off during circulation and then switch on their imaging capacity upon arrival at the target sites (tissue of interest). These smart nanoparticles contrast agent are self-assembled from pH sensitive amphiphilic polymer, loaded with Gadolinium (Gd3+) complex based Tl agent and then fitted with targeting biomolecules such as antibody, small molecules or DNA to increase its specificity toward the target of interest

Synthesis and characterization of Locust Bean Gum derivatives and their application in the production of nanoparticles

The development of LBG-based nanoparticles intending an application in oral immunization is presented. Nanoparticle production occurred by mild polyelectrolyte complexation, requiring the chemical modification of LBG. Three LBG derivatives were synthesized, namely a positively charged ammonium derivative (LBGA) and negatively charged sulfate (LBGS) and carboxylate (LBGC) derivatives. These were characterized by Fourier-transform infrared spectroscopy, elemental analysis, nuclear magnetic resonance spectroscopy, gel permeation chromatography, and x-ray diffraction. As a pharmaceutical application was aimed, a toxicological analysis of the derivatives was performed by both MTT test and LDH release assay. Several nanoparticle formulations were produced using LBGA or chitosan (CS) as positively charged polymers, and LBGC or LBGS as negatively charged counterparts, producing nanoparticles with adequate properties regarding an application in oral immunization.info:eu-repo/semantics/publishedVersio

Intrinsic and extrinsic resistive switching in a planar diode based on silver oxide nanoparticles

Resistive switching is investigated in thin-film planar diodes using silver oxide nanoparticles capped in a polymer. The conduction channel is directly exposed to the ambient atmosphere. Two types of switching are observed. In air, the hysteresis loop in the current–voltage characteristics is S-shaped. The high conductance state is volatile and unreliable. The switching is mediated by moisture and electrochemistry. In vacuum, the hysteresis loops are symmetric, N-shaped and exhibit a negative differential resistance region. The conductance states are non-volatile with good data retention, programming cycling endurance and large current modulation ratio. The switching is attributed to electroforming of silver oxide clusters

Human-derived NLS enhance the gene transfer efficiency of chitosan

Nuclear import is considered as one of the major limitations for non-viral gene delivery systems and the incorporation of nuclear localization signals (NLS) that mediate nuclear intake can be used as a strategy to enhance internalization of exogenous DNA. In this work, human-derived endogenous NLS peptides based on insulin growth factor binding proteins (IGFBP), namely IGFBP-3 and IGFBP-5, were tested for their ability to improve nuclear translocation of genetic material by non-viral vectors. Several strategies were tested to determine their effect on chitosan mediated transfection efficiency: co-administration with polyplexes, co-complexation at the time of polyplex formation, and covalent ligation to chitosan. Our results show that co-complexation and covalent ligation of the NLS peptide derived from IGFBP-3 to chitosan polyplexes yields a 2-fold increase in transfection efficiency, which was not observed for NLS peptide derived from IGFBP-5. These results indicate that the integration of IGFBP-NLS-3 peptides into polyplexes has potential as a strategy to enhance the efficiency of non-viral vectors.FCT: PTDC/BTM/ORG/28121/2017; PD/BD/52424/2013; SFRH/BD/76873/2011;PIRG-GA-2009-249314info:eu-repo/semantics/publishedVersio

Inhalable spray-dried chondroitin sulphate microparticles: effect of different solvents on particle properties and drug activity

Spray-drying stands as one of the most used techniques to produce inhalable microparticles, but several parameters from both the process and the used materials affect the properties of the resulting microparticles. In this work, we describe the production of drug-loaded chondroitin sulphate microparticles by spray-drying, testing the effect of using different solvents during the process. Full characterisation of the polymer and of the aerodynamic properties of the obtained microparticles are provided envisaging an application in inhalable tuberculosis therapy. The spray-dried microparticles successfully associated two first-line antitubercular drugs (isoniazid and rifabutin) with satisfactory production yield (up to 85%) and drug association efficiency (60%–95%). Ethanol and HCl were tested as co-solvents to aid the solubilisation of rifabutin and microparticles produced with the former generally revealed the best features, presenting a better ability to sustainably release rifabutin. Moreover, these presented aerodynamic properties compatible with deep lung deposition, with an aerodynamic diameter around 4 μm and fine particle fraction of approximately 44%. Finally, it was further demonstrated that the antitubercular activity of the drugs remained unchanged after encapsulation independently of the used solvent.Fundação para a Ciência e a Tecnologia | Ref. PTDC/DTP-FTO/0094/2012Fundação para a Ciência e a Tecnologia | Ref. UID/BIM/04773/2013Fundação para a Ciência e a Tecnologia | Ref. SFRH/BD/52426/2013Xunta de Galicia | Ref. ED481B 2018/071Ministerio de Ciencia e Innovación | Ref. IJCI-2016-27535Fundação para a Ciência e a Tecnologia | Ref. UID/Multi/04326/202