Encapsulation of gold nanostructures and oil-in-water nanocarriers in microgels with biomedical potential

Indexación: Scopus.Funding: This research was funded by FONDECYT 1161450, 1150744, 11130494 and 1170929, FONDEQUIP EQM160157, EQM170111, CONICYT-FONDAP 15130011, and CONICYT PhD Scholarship 21141137.Here we report the incorporation of gold nanostructures (nanospheres or nanorods, functionalized with carboxylate-end PEG) and curcumin oil-in-water (O/W) nanoemulsions (CurNem) into alginate microgels using the dripping technique. While gold nanostructures are promising nanomaterials for photothermal therapy applications, CurNem possess important pharmacological activities as reported here. In this sense, we evaluated the effect of CurNem on cell viability of both cancerous and non-cancerous cell lines (AGS and HEK293T, respectively), demonstrating preferential toxicity in cancer cells and safety for the non-cancerous cells. After incorporating gold nanostructures and CurNem together into the microgels, microstructures with diameters of 220 and 540 µm were obtained. When stimulating microgels with a laser, the plasmon effect promoted a significant rise in the temperature of the medium; the temperature increase was higher for those containing gold nanorods (11–12 ◦ C) than nanospheres (1–2 ◦ C). Interestingly, the incorporation of both nanosystems in the microgels maintains the photothermal properties of the gold nanostructures unmodified and retains with high efficiency the curcumin nanocarriers. We conclude that these results will be of interest to design hydrogel formulations with therapeutic applications. © 2018 by the authors.https://www.mdpi.com/1420-3049/23/5/120

Chitosan Based Polyelectrolyte Complexes as Potential Carrier Materials in Drug Delivery Systems

Chitosan has been the subject of interest for its use as a polymeric drug carrier material in dosage form design due to its appealing properties such as biocompatibility, biodegradability, low toxicity and relatively low production cost from abundant natural sources. However, one drawback of using this natural polysaccharide in modified release dosage forms for oral administration is its fast dissolution rate in the stomach. Since chitosan is positively charged at low pH values (below its pKa value), it spontaneously associates with negatively charged polyions in solution to form polyelectrolyte complexes. These chitosan based polyelectrolyte complexes exhibit favourable physicochemical properties with preservation of chitosan’s biocompatible characteristics. These complexes are therefore good candidate excipient materials for the design of different types of dosage forms. It is the aim of this review to describe complexation of chitosan with selected natural and synthetic polyanions and to indicate some of the factors that influence the formation and stability of these polyelectrolyte complexes. Furthermore, recent investigations into the use of these complexes as excipients in drug delivery systems such as nano- and microparticles, beads, fibers, sponges and matrix type tablets are briefly described

Pullulan-based nanoparticles as carriers for transmucosal protein delivery

Polymeric nanoparticles have revealed very effective in transmucosal delivery of proteins. Polysaccharides are among the most used materials for the production of these carriers, owing to their structural flexibility and propensity to evidence biocompatibility and biodegradability. In parallel, there is a preference for the use of mild methods for their production, in order to prevent protein degradation, ensure lower costs and easier procedures that enable scaling up. In this work we propose the production of pullulan-based nanoparticles by a mild method of polyelectrolyte complexation. As pullulan is a neutral polysaccharide, sulfated and aminated derivatives of the polymer were synthesized to provide pullulan with a charge. These derivatives were then complexed with chitosan and carrageenan, respectively, to produce the nanocarriers. Positively charged nanoparticles of 180-270 nm were obtained, evidencing ability to associate bovine serum albumin, which was selected as model protein. In PBS pH 7.4, pullulan-based nanoparticles were found to have a burst release of 30% of the protein, which maintained up to 24h. Nanoparticle size and zeta potential were preserved upon freeze-drying in the presence of appropriate cryoprotectants. A factorial design was approached to assess the cytotoxicity of raw materials and nanoparticles by the metabolic test MTT. Nanoparticles demonstrated to not cause overt toxicity in a respiratory cell model (Calu-3). Pullulan has, thus, demonstrated to hold potential for the production of nanoparticles with an application in protein delivery

NANOMEDICAMENTOS PARA EL TRATAMIENTO LOCALIZADO DE PATOLOGÍAS PULMONARES

El objetivo de la presente memona se ha dirigido al diseño y evaluación de nanoestructuras para el tratamiento localizado de patologías pulmonares. En una primera etapa, se han desarrollado nanopartículas de quitosano, en combinación con ácido hialurónico o con carboximetil-~ciclodextrina, conteniendo la macromolécula hidrofílica heparina. Dichos sistemas fueron evaluados en relación a su capacidad de mejora de eficacia de la heparina sobre mastocitos, en el tratamiento del asma bronquial. Se demostró por microscopía confocal de fluorescencia que los nanosistemas eran internalizados por mastocitos de rata y, en el caso de los nanosistemas con ciclodextrinas, se consiguió mejorar de manera significativa el efecto de la heparina sobre la inhibición de la liberación de histamina en mastocitos. La segunda parte del trabajo se orientó al diseño de un nuevo nanosistema, consistente en nanocápulas de ácido hialurónico, con el fin último de dirigirlo al tratamiento del cáncer de pulmón. Los nanosistemas incrementaron significativamente el efecto citotóxico del antitumoral hidrofóbico docetaxel, sobre la línea celular de cáncer de pulmón NCI-H460, hecho que se atribuyó a la internalización de las nanocápsulas y la liberación intracelular del docetaxel. Estos resultados resaltan el enorme interés de los nanosistemas desarrollados para la liberación intracelular de fármacos en el tratamiento de enfermedades pulmonares

Flow Chemistry to Control the Synthesis of Nano and Microparticles for Biomedical Applications

International audienc

Influence of the particle size of encapsulated chia oil on the oil release and bioaccessibility during <i>in vitro</i> gastrointestinal digestion

Among vegetable oils, chia oil has been gaining interest in recent years due to its high linolenic acid content (ALA, 18:3 ω3). The aim of this work was to study the influence of the particle size of encapsulated purified chia oil (PCO) on the encapsulation efficiency and PCO release during in vitro digestion. PCO micro- and nano-sized particles with sodium alginate (SA) as an encapsulating agent (ME-PCO-SA and NE-PCO-SA) were designed by micro and nano spray-drying, respectively, applying a central composite plus star point experimental design. NE-PCO-SA showed a smaller particle size and higher encapsulation efficiency of PCO than ME-PCO-SA (0.16 μm vs. 3.5 μm; 98.1% vs. 92.0%). Emulsions (NE-PCO and ME-PCO) and particles (NE-PCO-SA and ME-PCO-SA) were subjected to in vitro static gastrointestinal digestion. ME-PCO and NE-PCO showed sustained oil release throughout the three phases of digestion (oral, gastric and intestinal phases), whereas the PCO release from ME-PCO-SA and NE-PCO-SA occurred mainly in the intestinal phase, showing the suitability of sodium alginate as an intestine-site release polymer. Nano-sized particles showed a significantly higher PCO release after in vitro digestion (NE-PCO-SA, 78.4%) than micro-sized particles (ME-PCO-SA, 69.8%), and also higher bioaccessibility of individual free fatty acids, such as C18:3 ω-3 (NE-PCO-SA, 23.6%; ME-PCO-SA, 7.9%), due to their greater surface area. However, when ME-PCO-SA and NE-PCO-SA were incorporated into yogurt, the PCO release from both particle systems after the digestion of the matrix was similar (NE-PCO-SA, 58.8%; ME-PCO-SA-Y, 61.8%), possibly because the calcium ions contained in the yogurt induced partial ionic gelation of SA, impairing the PCO release. Sodium alginate spray-dried micro and nanoparticles showed great potential for vehiculation of omega-3 rich oils in the design of functional foods

Polymeric Nanoparticles for Increasing Oral Bioavailability of Curcumin

International audienceDespite the promising biological and antioxidant properties of curcumin, its medical applications are limited due to poor solubility in water and low bioavailability. Polymeric nanoparticles (NPs) adapted to oral delivery may overcome these drawbacks. Properties such as particle size, zeta potential, morphology and encapsulation efficiency were assessed. Then, the possibility of storing these NPs in a solid-state form obtained by freeze-drying, in vitro curcumin dissolution and cytocompatibility towards intestinal cells were evaluated. Curcumin-loaded Eudragit ® RLPO (ERL) NPs showed smaller particle diameters (245 ± 2 nm) and better redispersibility after freeze-drying than either poly(lactic-co-glycolic acid) (PLGA) or polycaprolactone (PCL) NPs. The former NPs showed lower curcumin encapsulation efficiency (62%) than either PLGA or PCL NPs (90% and 99%, respectively). Nevertheless, ERL NPs showed rapid curcumin release with 91 ± 5% released over 1 h. The three curcumin-loaded NPs proposed in this work were also compatible with intestinal cells. Overall, ERL NPs are the most promising vehicles for increasing the oral bioavailability of curcumin

Synthesis of tuneable amphiphilic-modified polyketone polymers, their complexes with 5,10,15,20-tetrakis-(4-sulfonatophenyl)porphyrin, and their role in the photooxidation of 1,3,5-triphenylformazan confined in polymeric nanoparticles

A series of amphiphilic polymers bearing aliphatic secondary amines and hydroxyl groups have been synthesized showing different hydrophilic/hydrophobic balance. The synthesis is performed through the Paal-Knorr modification of a polyketone comprising both ethylene and propylene comonomers with N-(2-hydroxyethyl)ethylenediamine. The values of dicarbonyl conversion achieved were 19, 35, 51, and 63%, which allowed controlling the amphiphilia of the polymers: a lower carbonyl conversion degree implies a higher hydrophobia. On the other hand, photodegradation studies of a model nanosized pollutant pigment comprised of 1,3,5-triphenylformazan nanoparticles stabilized by poly(sodium 4-styrenesulfonate) have been performed in the absence and in the presence of the photocatalyst 5,10,15,20-tetrakis-(4-sulfonatophenyl)porphyrin, showing no catalytic action, since electrostatic repulsion minimize molecular contacts between the reactants. However, the synthesized polymers allow overcoming this problem. Due to their amphiphila, the polymers showing dicarbonyl conversion values of 35, 51, and 63% form complexes with the porphyrin and stabilize its non-self-aggregated tetraanionic form in water from basic pH up to pH 1.74, 1.82, and 2.76, respectively, the differences related with the polymeric relative hydrophilic/hydrophobic balance. Only the amphiphilic polymer showing a conversion degree of 35% acts as an adequate vehicle for the dye to photocatalyze the oxidation of 1,3,5-triphenylformazan confined in the nanoparticles, highlighting the potential of the Paal-Knorr modification of polyketones to achieve a fine tunning of polymeric properties to obtain a specific functionality: the positive charge of the complex and the high hydrophobia of the tuned polymer allow, respectively, attractive long-range electrostatic interactions with the nanoparticles and diffusion of the reactants into the nanoparticle hydrophobic environment