A VACCINE PROTOTYPE USING BACULOVIRUS EXPRESSION SYSTEM FOR THE CONTROL OF AVIAN INFLUENZA VIRUS

A clade 1 sequence of H5 haemaglutinin from an Asian Avian H5N1 isolate was used as a the template to chemically synthetize a codon optimized version for expression in insect cells. A single clone was chosen for expression optimization and changes were introduced in order to maximize the amount of protein to be produced and to resemble another sequence demonstrated to be present in an isolate causing disease in Humans. Preliminary analysis at lab scale have shown promising yields of the haemaglutinin using an activity titration assay and an ELISA-based detection method. Optimization of the cell seeding, MOI, and time of harvest have provided valuable data to ensure sufficient production of the protein compatible with scale up application. In order to test the biological activity of the expressed protein and its ability to trigger an immune response, oil/water emulsions of different amounts of the protein were administered to SPF chickens and antibodies levels were detected using an ELISA-based system and HI titration. Both approaches were able to demonstrate seroconvertion and a dose-response curve was observed among the different doses. Altogether, results support the feasibility of the genetic contruct and the expression platform to produce bulk amounts of protein which could be used for different purposes

Fabrication and characterisation of poly(sulfonated) and poly(sulfonic acid) dissolving microneedles for delivery of antibiotic and antifungal agents

Skin and soft tissue infections (SSTIs) arise from microbial ingress into the skin. In this study, poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (polyAMPS), which has been reported to exhibit antimicrobial properties was synthesised for the manufacture of microarray patches (MAPs). The free acid and sodium salt of polyAMPS with controlled molar masses and narrow dispersity were synthesised via reversible addition − fragmentation chain-transfer (RAFT) polymerisation reaction with a monomer conversion of over 99%, as determined by 1H NMR. The polymers were shown to be biocompatible when evaluated using a fibroblast dermal cell line while agar plating assay using cultures of C. albican demonstrated that the acid form of polyAMPS exhibited antimicrobial inhibition, which is potentiated in the presence of antimicrobial agents. The synthesised polymers were then used to fabricate dissolving MAPs, which were loaded with either ITRA or levofloxacin (LEV). The MAPs displayed acceptable mechanical resistance and punctured ex vivo skin to a depth of 600 µm. Skin deposition studies revealed that the MAPs were able to administer up to ∼ 1.9 mg of LEV (delivery efficiency: 94.7%) and ∼ 0.2 mg of ITRA (delivery efficiency: 45.9%), respectively. Collectively, the synthesis and development of this novel pharmaceutical system may offer a strategy to manage SSTIs.<br/

Conflictos Socioambientales en Jalisco

El PAP Alter CÓDIGO, en su periodo de otoño, trabajó en colaboración con la Escuela para Defensoras del Territorio Benita Galeana, para dar continuación al proyecto de la creación de una campaña de fondeo que busca recaudar fondos que se destinen a la mejora del diseño estructural y del servicio que brindan. Se fijaron objetivos para la creación de contenido, que sea coherente con los valores de la Escuela y con los objetivos de la campaña. Esto se hizo para que se le de reconocimiento a la Escuela para Defensoras, al Mercadito Flor de Luna, a la situación socioambiental en la que vivimos y a las alternativas que existen. Por otro lado, se fijaron objetivos específicos internos para la organización del equipo PAP. Este proyecto se realizó a partir y a la par de una metodología: la etnografía. Esta ayuda a que comprendamos mejor la forma en la que las personas se desarrollan, cómo viven, qué quieren expresar, y nos da bases para poder adaptar el contenido a esto. Al final del proyecto, se entregó toda la producción de la campaña, es decir, la programación y contenidos listos para que se lance la campaña, además de manuales que explican cada uno de los segmentos de la creación de la misma para que pueda ser replicable tanto por el mismo PAP como por las integrantes de la Escuela de Defensoras

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Poly(caprolactone)/lignin-based 3D-printed dressings loaded with a novel combination of bioactive agents for wound-healing applications

Curcumin (CUR) has been shown to possess significant anti-inflammatory properties and significant wound healing potential. Additionally, lignin (LIG) is a renewable biomacromolecule with well-known antioxidant and antimicrobial properties, which makes this biomacromolecule a good candidate to be included in medical materials, such as wound dressings. Although many of the wound dressings used at present have interesting features, some are limited in terms of antibacterial properties. To address these limitations, in the present work, both CUR and LIG were combined with poly(caprolactone) (PCL), a biocompatible polymer, to obtain dressings with antioxidant and antimicrobial properties for wound healing treatment. Moreover, D-Panthenol (DPA) was included in the composite materials formulation due to its skin regenerative ability by enhancing epidermal differentiation. Semi-solid extrusion (SSE) 3D printing was used to manufacture wound dressings without the use of any solvents. 3D-printed dressings provided a sustained DPA and CUR release for periods of up to 4 and 35 days, respectively. A DPPH (2,2-diphenyl-1-picrylhydrozyl) assay was performed confirming that the presence of LIG and CUR provided antioxidant properties to the 3D-printed dressings. Additionally, these 3D-printed materials showed a marked resistance to adherence of Staphylococcus aureus when compared to the PCL control 3D-printed samples, resulting in substantial reductions of up to 89.9% and 98.9% after incubation periods of 4 h and 24 h respectively. Although, all of the 3D-printed materials were able to provide a supportive environment for cellular attachment, viability and growth, the combination of both bioactive compounds CUR and DPA exhibited the most significant values for cell viability and proliferation. In vivo wound healing study performed in Wistar rats showed that dressings containing these novel two compounds CUR and DPA exhibited marked improvement at any stage of the treatment process. Finally, histological examination revealed that dressings loaded with CUR and DPA also showed the best outcomes for all the evaluated parameters: (i) epithelisation, (ii) inflammatory reaction, (iii) proliferation rate of fibroblast and (iv) neoangiogenesis.Wellcome Trust UNS4004

Reservoir-type intranasal implants for sustained release of risperidone: a potential alternative for long-term treatment of schizophrenia

To overcome the challenges of the blood-brain barrier for drug delivery to the central nervous system (CNS), intranasal implants were developed to improve the management of CNS conditions, such as schizophrenia. In the present work, we developed and characterised a drug-containing implant consisting of two parts: a core layer made from risperidone (RIS) and water-soluble polymers, including poly(vinylpyrrolidone) (PVP) and poly(ethylene glycol) (PEG), and a coating layer made of poly(caprolactone) (PCL) membrane. The obtained implants, where the core layer contained 75% w/w risperidone, were characterised using several techniques: scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR). Moreover, the in vitro release profile of RIS was studied, showing that the PCL membrane could extend the release of RIS from 2 days up to 100 days. The in vitro release profile of the PCL-coated implant exhibited a linear release over the first 10 days, followed by a slower release rate that reached another linear phase up to 40 days. Subsequently, the drug release rates progressively slowed down. Finally, the results of in vitro biocompatibility studies indicated that the intranasal implants were biocompatible and non-cytotoxic. These findings suggest that the implants prepared in this work have the potential to provide long-acting drug delivery for targeting the brain.<br/

Fabrication and characterisation of poly (sulfonated) and poly (sulfonic acid) dissolving microneedles for delivery of antibiotic and antifungal agents

Skin and soft tissue infections (SSTIs) arise from microbial ingress into the skin. In this study, poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (polyAMPS), which has been reported to exhibit antimicrobial properties was synthesised for the manufacture of microarray patches (MAPs). The free acid and sodium salt of polyAMPS with controlled molar masses and narrow dispersity were synthesised via reversible addition − fragmentation chain-transfer (RAFT) polymerisation reaction with a monomer conversion of over 99%, as determined by 1H NMR. The polymers were shown to be biocompatible when evaluated using a fibroblast dermal cell line while agar plating assay using cultures of C. albican demonstrated that the acid form of polyAMPS exhibited antimicrobial inhibition, which is potentiated in the presence of antimicrobial agents. The synthesised polymers were then used to fabricate dissolving MAPs, which were loaded with either ITRA or levofloxacin (LEV). The MAPs displayed acceptable mechanical resistance and punctured ex vivo skin to a depth of 600 µm. Skin deposition studies revealed that the MAPs were able to administer up to ∼ 1.9 mg of LEV (delivery efficiency: 94.7%) and ∼ 0.2 mg of ITRA (delivery efficiency: 45.9%), respectively. Collectively, the synthesis and development of this novel pharmaceutical system may offer a strategy to manage SSTIs.<br/

Liposome-loaded polymeric microneedles for enhanced skin deposition of rifampicin

Methicillin-resistant Staphylococcus aureus (MRSA) is a prevailing bacterial pathogen linked to superficial skin and soft tissue infections (SSTIs). Rifampicin (RIF), a potent antibiotic against systemic and localised staphylococcal infections, faces limitations due to its low solubility. This constraint hampers its therapeutic potential for MRSA-induced SSTIs. To address this, an advanced liposomal system was designed for efficient dermal RIF delivery. Rifampicin-loaded liposomes (LipoRIF) were embedded within polymeric dissolving microneedles (DMNs) to enable targeted intradermal drug delivery. A robust Design of Experiment (DoE) methodology guided the systematic preparation and optimisation of LipoRIF formulations. The optimal LipoRIF formulation integrated within polymeric DMNs. These LipoRIF-DMNs exhibited favourable mechanical properties and effective skin insertion characteristics. Notably, in vitro assays on skin deposition unveiled a transformative result – the DMN platform significantly enhanced LipoRIF deposition within the skin, surpassing LipoRIF dispersion alone. Moreover, LipoRIF-DMNs displayed minimal cytotoxicity toward cells. Encouragingly, rigorous in vitro antimicrobial evaluations demonstrated LipoRIF-DMNs' capacity to inhibit MRSA growth compared to the control group. LipoRIF-DMNs propose a potentially enhanced, minimally invasive approach to effectively manage SSTIs and superficial skin ailments stemming from MRSA infections.Wellcome Trust WT094085M