Thiolated-polymer-based nanoparticles as an avant-garde approach for anticancer therapies—Reviewing thiomers from chitosan and hyaluronic acid

Thiomers (or thiolated polymers) have broken through as avant-garde approaches in anticancer therapy. Their distinguished reactivity and properties, closely linked to their final applications, justify the extensive research conducted on their preparation and use as smart drug-delivery systems (DDSs). Multiple studies have demonstrated that thiomer-rich nanoformulations can overcome major drawbacks found when administering diverse active pharmaceutical ingredients (APIs), especially in cancer therapy. This work focuses on providing a complete and concise review of the synthetic tools available to thiolate cationic and anionic polymers, in particular chitosan (CTS) and hyaluronic acid (HA), respectively, drawing attention to the most successful procedures. Their chemical reactivity and most relevant properties regarding their use in anticancer formulations are also discussed. In addition, a variety of NP formation procedures are outlined, as well as their use in cancer therapy, particularly for taxanes and siRNA. It is expected that the current work could clarify the main synthetic strategies available, with their scope and drawbacks, as well as provide some insight into thiomer chemistry. Therefore, this review can inspire new research strategies in the development of efficient formulations for the treatment of cancer

Hábitos y normas de seguridad recomendadas en un laboratorio de entorno químico

Las nuevas normativas que la Legislación impone relativas a los hábitos saludables y de seguridad que deben cumplirse en los laboratorios, han supuesto una revolución muy positiva en estos entornos de trabajo. Estos cambios están siendo posibles, gracias a la introducción de mejores infraestructuras, que están posibilitando al investigador la integración en su trabajo de nuevas maneras de trabajar, encaminadas a minimizar tanto los riesgos de accidentes como el impacto de sus investigaciones en el medioambiente. Las normas que se exponen a continuación han sido elaboradas por la Comisión de Prevención de Riesgos del Departamento de Química Orgánica y Farmacéutica, de la Facultad de Farmacia de Sevilla, con objeto de ser de seguidas por todos sus miembros. Estas normas son completamente extrapolables a cualquier laboratorio de entorno químico, en el que convivan por un lado disolventes orgánicos o inorgánicos y reactivos químicos, y por otro, personal altamente cualificado o de nueva incorporación a este tipo de entornos. El documento se divide en varias partes: 1) Normas de obligado cumplimiento, 2) Recomendaciones, y 3) Formulario de aceptación de las Normas de Trabajo anteriores

Nanostructured Chitosan-Based Biomaterials for Sustained and Colon-Specific Resveratrol Release

In the present work, we demonstrate the preparation of chitosan-based composites as vehicles of the natural occurring multi-drug resveratrol (RES). Such systems are endowed with potential therapeutic effects on inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis, through the sustained colonic release of RES from long-lasting mucoadhesive drug depots. The loading of RES into nanoparticles (NPs) was optimized regarding two independent variables: RES/polymer ratio, and temperature. Twenty experiments were carried out and a Box–Behnken experimental design was used to evaluate the significance of these independent variables related to encapsulation efficiency (EE). The enhanced RES EE values were achieved in 24 h at 39 °C and at RES/polymer ratio of 0.75:1 w/w. Sizes and polydispersities of the optimized NPs were studied by dynamic light scattering (DLS). Chitosan (CTS) dispersions containing the RES-loaded NPs were ionically gelled with tricarballylic acid to yield CTS-NPs composites. Macro- and microscopic features (morphology and porosity studied by SEM and spreadability), thermal stability (studied by TGA), and release kinetics of the RES-loaded CTS-NPs were investigated. Release patterns in simulated colon conditions for 48 h displayed significant differences between the NPs (final cumulative drug release: 79–81%), and the CTS-NPs composites (29–34%)

pH-Responsive Polymeric Nanoparticles as Drug Delivery Systems

Micelles are excellent devices to be used as controlled drug delivery systems since they exhibit the ability to protect the drug or encapsulated substance from the routes of degradation until they reach the site of action: moreover, they can pass through biological barriers and reach intracellular compartments. In addition, when a drug is administered and released from the dosage form, the kinetic behavior of the drug depends largely on their chemical structure. However, when the drug is immersed at the core of a NP, the physicochemical properties that actually affect the distribution of the drug in the body are those from the latter. As a result, this approach controls drug release, diminishing side effects and increasing therapeutic rates. In the present work novel smart micelles have been prepared and tested as drug delivery systemsMinisterio de Economía y Competitividad-Grant MAT2016-77345-C3-2-PJunta de Andalucía-Grant P12-FQM-155

Synthesis and Characterization of New Carbohydrate-based Polyureas

A batch of linear [m,n]-type sugar-based polyureas was synthesized by polyaddition reaction in solution from hexamethylene diisocyanate or 4,4’-methylene-bis(phenyl isocyanate) with the acyclic 2,3,4-tri-O-methyl-1,5- diamino-alditols having L-arabino, or xylo confi guration or the bicyclic 1,6-diamino-1,6-dideoxy-2,4:3,5-diO-methylene-D-glucitol. The polymers were obtained in good yields and fair molecular weights. All these polyureas were semicrystalline materials showing well-defi ned melting transition within the 86−171°C range, with Tg s being dependent on the aliphatic or aromatic nature of the diisocyanate used, and on the cyclic or acyclic chemical structure of the sugar moiety. They were found to be stable up to around 240°C, decomposing at higher temperatures through a one- or two-stage mechanism.Ministerio de Ciencia e Innovación de España (MICINN) - MAT2009-14053-C02-02Junta de Andalucía - P07-FQM-0264

Nueva composición de conjugados de chitosan o derivados con tiolactonas

La presente invención se refiere a conjugados del chitosan (o sus derivados) con tiolactonas (síntesis y estructuras químicas), en las composiciones cosméticas, biomédicas-farmacéuticas que contienen dichos conjugados, y a sus aplicaciones, que presentan las siguientes propiedades: no tóxicos, biodegradables, con excelentes propiedades de mucoadhesión, cohesión e inhibición enzimática, con propiedades mejoradas de permeabilidad, captación celular y gran estabilidad como agentes de recubrimiento de cánulas y otros dispositivos médicos y como sistemas transportadores de fármacos, esto es, con largos tiempos de permanencia de los principios activos englobados, lo que garantiza un excelente control en la liberación de los fármacos incluidos en la formulación y además, capaces de gelificar en presencia de oxígeno.Españ

Síntesis de poliamidas quirales análogas a los nylons 2 y 3 a partir de hidratos de carbono y su caracterización físico-química

La industria de los polímeros comenzó a desarrollarse en el siglo XIX basándose en la modificación de ciertos polímeros naturales, por ejemplo, algunos hidratos de carbono como el almidón, la celulosa y la caseína, que fueron finalmente sustituidos por o

Synthetic Polymers from Sugar-Based Monomers

Ministerio de Economía y Competitividad MAT2012- 38044-C03-01Junta de Andalucía Grant P12-FQM-155

Chitosan-based hydrogels obtained via photoinitiated click polymer IPN reaction

Chitosan (CTS) is a polysaccharide with a wide variety of applications in the biomedical field, owing to its outstanding disinfectant properties, biocompatibility and biodegradability, but with limited mechanical properties. The proposed strategy to improve CTS-based hydrogel properties in this study is the formation of a semi-interpenetrating polymer network (semi-IPN). In this way, a photo-initiated radical click reaction was proposed to obtain a synthetic polymer, whose components were included in a CTS solution, resulting in the semi-IPN network after UV illumination. Different crosslinking degrees (CD) and CTS/polymer ratios were evaluated through rheological characterization, along with an assessment of both variables based on an experimental model design, obtaining that, for every CTS/polymer ratio, intermediate values of CD (8 %) offered the best rheological properties. In addition, chemical and microstructural characterization were carried out for selected hydrogels, obtaining consistent results according to rheological characterization, as the 1/1 CTS/polymer ratio with CD 8 % hydrogel displayed the most homogeneous pore size and distribution, consequently leading to the best rheological performance

Structurally simple redox polymersomes for doxorubicin delivery

A simple redox amphiphilic tri-block copolyurethane capable of assembling in the form of polymersome has been easily synthesized. Thus, the hydrophobic core is constituted by a central block containing multiple disulfide linkages, and the hydrophilic segments are formed by poly(ethylene glycol) methyl ether (mPEG2000). The disulfide-containing block was obtained by the reaction of commercial 2,2′-dithiodiethanol and hexamethylene diisocyanate, which was further reacted with the mentioned PEG to afford the tri-block copolymer nominated as mPEG-PDH-mPEG, in above 80% yield. This copolymer self-assembled into polymersomes of size around 130 nm by the water addition/solvent evaporation method. Different systems of doxorubicin/polymer ratios (D/P 0.5 – 3) were prepared and the drug loading (%DL) and encapsulation efficiency (%EE) were studied by visible light absorbance measurements. Systems D/P 2 and 3 showed DL up to 62% and 69%, respectively. Besides that, D/P 1 and 2 presented EE values in the order of 83%. Finally, the release of DOX in the presence of 0.01 M glutathione solutions at 37 °C, was 74.6% and 82% from D/P 3 and D/P 0.5, respectively, after 5 days of incubation. Further studies on other water-soluble drugs for the cancer treatment would be of great interest to demonstrate the high potential of these redox polymeric systems.Ministerio de Economía y Competitividad de España - MAT2016-77345-C3-2-PJunta de Andalucía - P12-FQM-155