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

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

Totally Organic Redox-Active pH-Sensitive Nanoparticles Stabilized by Amphiphilic Aromatic Polyketones

Amphiphilic aromatic polymers have been synthesized by grafting aliphatic polyketones with 4-(aminomethyl)benzoic acid at different molar ratios via the PaalKnorr reaction. The resulting polymers, showing diketone conversion degree of 16%, 37%, 53%, and 69%, have been complexed with the redox-active 2,3,5-triphenyl-2H-tetrazolium chloride, a precursor molecule with which aromaticaromatic interactions are held. Upon addition of ascorbic acid to the complexes, in situ reduction of the tetrazolium salt produced 1,3,5-triphenylformazan nanoparticles stabilized by the amphiphilic polymers. The stabilized nanoparticles display highly negative zeta potential [-(35-70) mV] and hydrodynamic diameters in the submicron range (100-400 nm). Nonaromatic polyelectrolytes or hydrophilic aromatic copolymers showing low linear aromatic density and high linear charge density such as acrylate/maleate and sulfonate/maleate-containing polymers were unable to stabilize formazan nanoparticles synthesized by the same method. The copolymers studied here bear uncharged nonaromatic comonomers (unreacted diketone units) as well as charged aromatic comonomers, which furnish amphiphilia. Thus, the linear aromatic density and the maximum linear charge density have the same value for each copolymer, and the hydrophilic/hydrophobic balance varies with the diketone conversion degree. The amphiphilia of the copolymers allows the stabilization of the nanoparticles, even with the copolymers showing a low linear aromatic density. The method of nanoparticle synthesis constitutes a simple, cheap, and green method for the production of switchable totally organic, redox-active, pH-sensitive nanoparticles that can be reversibly turned into macroprecipitates upon pH changing.FONDECYT 1050899 CONICYT-FONDAP 15130011 CONICYT, Chile 7213004

Efficacy of stem cell secretome loaded in hyaluronate sponge for topical treatment of psoriasis

Abstract Psoriasis vulgaris is an inflammatory disease characterized by distinctive skin lesions and dysregulated angiogenesis. Recent research uses stem cell secretion products (CM); a set of bioactive factors with therapeutic properties that regulate several cellular processes, including tissue repair and angiogenesis. The aim of this work was to evaluate the effect of CM of Wharton's gelatin MSC (hWJCM) in a treatment based on the bioactivation of a hyaluronic acid matrix (HA hWJCM) in a psoriasiform‐like dermatitis (PD) mouse model. A preclinical study was conducted on PD mice. The effect of hWJCM, Clobetasol (Clob) gold standard, HA Ctrl, and HA hWJCM was tested topically evaluating severity of PD, mice weight as well as skin, liver, and spleen appearance. Treatment with either hWJCM, HA Ctrl or HA hWJCM, resulted in significant improvement of the PD phenotype. Moreover, treatment with HA hWJCM reduced the Psoriasis Area Severity Index (PASI), aberrant angiogenesis, and discomfort associated with the disease, leading to total recovery of body weight. We suggest that the topical application of HA hWJCM can be an effective noninvasive therapeutic solution for psoriasis, in addition to other skin diseases, laying the groundwork for future studies in human patients