Bioinspired oxidation-resistant catechol-like sliding ring polyrotaxane hydrogels

Adaptable hydrogels have been used in the biomedical field to address several pathologies, especially those regarding tissue defects. Here, we describe unprecedented catechol-like functionalized polyrotaxane (PR) polymers able to form hydrogels. PR were functionalized with the incorporation of hydroxypyridinone (HOPO) moieties into the polymer backbone, with a degree of substitution from 4 to 22%, depending on the PR type. The hydrogels form through the functionalized supramolecular systems when in contact with a Fe(III) solution. Despite the hydrogel formation being at physiological pH (7.4), the HOPO derivatives are extremely resistant to oxidation, unlike common catechols; consequently, they prevent the formation of quinones, which can lead to irreversible bounds within the matrix. The resulting hydrogels demonstrated properties lead to unique hydrogels with improved mechanical behavior obtained by metallic coordination crosslinking, due to the synergies of the sliding-ring PR and the non-covalent (reversible) catechol analogues. Following this strategy, we successfully developed innovative, cytocompatible, oxidative-resistant, and reversible crosslinked hydrogels, with the potential of being used as structural self-materials for a variety of applications, including in the biomedical field.publishe

Microemulsions for colorectal cancer treatments: general considerations and formulation of methotrexate

[Abstract] Microemulsions combine the advantages of emulsions with those of nanocarriers, overcoming the stability problems of the former and providing facile scalable systems with compartments adequate for high drug loadings. Recently, microemulsions are gaining attention in the formulation of anticancer drugs not only for topical treatment, but also for systemic delivery as well as for the development of theranostic systems. The aim of this paper is two-fold. First, an updated review about general features, preparation, characterization and pharmaceutical applications, with a special focus on colorectal cancer, is provided. Second, a case study of formulation of methotrexate in microemulsions is presented. Various essential oils (menthol, trans-anethole, α-tocopherol) and surfactants (TPGS-l000, Maxemul 6112, Noigen RN-20) were investigated for the preparation of o/w microemulsions for the delivery of methotrexate, and the ability of methotrexate-loaded microemulsions to inhibit cancer cell growth was then evaluated. Disregarding the surfactants used, menthol and trans-anethole led to cytotoxic microemulsions, whereas α-tocopherol based-formulations induced cell proliferation. These findings highlight the role that the oily component may play in the efficacy and safety of the microemulsions.México. Consejo Nacional de Ciencia y Tecnologia; No. CB-2011/ 168472Ministerio de Economia y Competitividad; SAF2014-52632-RRed Gallega de Investigación sobre Cáncer Colorrectal; R2014/03

A novel hanging spherical drop system for the generation of cellular spheroids and high throughput combinatorial drug screening

We propose a novel hanging spherical drop system for anchoring arrays of droplets of cell suspension based on the use of biomimetic superhydrophobic flat substrates, with controlled positional adhesion and minimum contact with a solid substrate. By facing down the platform, it was possible to generate independent spheroid bodies in a high throughput manner, in order to mimic in vivo tumour models on the lab-on-chip scale. To validate this system for drug screening purposes, the toxicity of the anti-cancer drug doxorubicin in cell spheroids was tested and compared to cells in 2D culture. The advantages presented by this platform, such as feasibility of the system and the ability to control the size uniformity of the spheroid, emphasize its potential to be used as a new low cost toolbox for high-throughput drug screening and in cell or tissue engineering.The authors thank the precious help of Alessandra Zonari and Rui Domingues for capturing the confocal images. The authors acknowledge the financial support from the FCT-Fundacao para a Ciencia e para a Tecnologia through the Ph.D. grants with the references SFRH/BD/73119/2010, SFRH/BD/69529/2010 and SFRH/BD/71396/2010. We acknowledge the financial support of FEDER through the program Operacional Factores de Competitividade - COMPETE and from FCT - the Fundacao para a Ciencia e a Tecnologia under the project PTDC/CTM-BIO/1814/2012. We also thank the support by the European Research Council grant agreement ERC-2012-ADG 20120216-321266 for the project ComplexiTE

Antioxidant PLA Composites Containing Lignin for 3D Printing Applications: A Potential Material for Healthcare Applications

Lignin (LIG) is a natural biopolymer with well-known antioxidant capabilities. Accordingly, in the present work, a method to combine LIG with poly(lactic acid) (PLA) for fused filament fabrication applications (FFF) is proposed. For this purpose, PLA pellets were successfully coated with LIG powder and a biocompatible oil (castor oil). The resulting pellets were placed into an extruder at 200 °C. The resulting PLA filaments contained LIG loadings ranging from 0% to 3% (w/w). The obtained filaments were successfully used for FFF applications. The LIG content affected the mechanical and surface properties of the overall material. The inclusion of LIG yielded materials with lower resistance to fracture and higher wettabilities. Moreover, the resulting 3D printed materials showed antioxidant capabilities. By using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, the materials were capable of reducing the concentration of this compound up to ca. 80% in 5 h. This radical scavenging activity could be potentially beneficial for healthcare applications, especially for wound care. Accordingly, PLA/LIG were used to design meshes with different designs for wound dressing purposes. A wound healing model compound, curcumin (CUR), was applied in the surface of the mesh and its diffusion was studied. It was observed that the dimensions of the meshes affected the permeation rate of CUR. Accordingly, the design of the mesh could be modified according to the patient’s needsThis work was supported by the Wellcome Trust Biomedical Vacation Scholarship (SS 213361/Z/18/Z) and the Society for Applied Microbiology Student Placement ScholarshipS

Fabrication and characterization of Eri silk fibers-based sponges for biomedical application

Cocoon-derived semi-domesticated Eri silk fibers still lack exploitation for tissue engineering applications due to their poor solubility using conventional methods. The present work explores the ability to process cocoon fibers of non-mulberry Eri silk (Samia/Philosamia ricini) into sponges through a green approach using ionic liquid (IL) â 1-buthyl-imidazolium acetate as a solvent. The formation of β-sheet structures during Eri silk/IL gelation was acquired by exposing the Eri silk/IL gels to a saturated atmosphere composed of two different solvents: (i) isopropanol/ethanol (physical stabilization) and (ii) genipin, a natural crosslinker, dissolved in ethanol (chemical crosslinking). The sponges were then obtained by freeze-drying. This approach promotes the formation of both stable and ordered non-crosslinked Eri silk fibroin matrices. Moreover, genipin-crosslinked silk fibroin sponges presenting high height recovery capacity after compression, high swelling degree and suitable mechanical properties for tissue engineering applications were produced. The incorporation of a model drug â ibuprofen â and the corresponding release study from the loaded sponges demonstrated the potential of using these matrices as effective drug delivery systems. The assessment of the biological performance of ATDC5 chondrocyte-like cells in contact with the developed sponges showed the promotion of cell adhesion and proliferation, as well as extracellular matrix production within two weeks of culture. Spongesâ intrinsic properties and biological findings open up their potential use for biomedical applications.The authors SSS, DSC, MBO, NMO acknowledge financial support from Portuguese Foundation for Science and Technology – FCT (Grants SFRH/BPD/45307/2008, SFRH/BPD/85790/2012, SFRH/BD/71396/2010 and SFRH/BD/73172/2010, respectively), ‘‘Fundo Social Europeu” – FSE, and ‘‘Programa Diferencial de Potencial Humano POPH”. This work is also financially supported by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n REGPOT-CT2012-316331-POLARIS and from Fundação para a Ciência e Tecnologia (FCT) through the project ENIGMA – PTDC/EQU-EPR/121491/2010. The laboratory work of SCK is supported by Department of Biotechnology and Indian Council of Medical Research, Govt of India. SCK and RLR acknowledge their short visits either Institutes. SCK is also grateful to 3B´ s Research Group- Biomaterials, Biodegradables and Biomimetics, University of Minho, Portugal for providing facilities during his short visit

Role of age and comorbidities in mortality of patients with infective endocarditis

Purpose: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. Methods: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015. Patients were stratified into three age groups:<65 years, 65 to 80 years, and = 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. Results: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 = 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients =80 years who underwent surgery were significantly lower compared with other age groups (14.3%, 65 years; 20.5%, 65-79 years; 31.3%, =80 years). In-hospital mortality was lower in the <65-year group (20.3%, <65 years;30.1%, 65-79 years;34.7%, =80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%, =80 years; p = 0.003).Independent predictors of mortality were age = 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI = 3 (HR:1.62; 95% CI:1.39–1.88), and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared, the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. Conclusion: There were no differences in the clinical presentation of IE between the groups. Age = 80 years, high comorbidity (measured by CCI), and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Neutral and cationic chelidonate coordination polymers with N,N′-bridging ligands

The biomolecule chelidonic acid (H2chel, 4-oxo-4H-pyran-2,6-dicarboxylic acid) has been used to build new coordination polymers with the bridging N,N′-ligands 4,4′-bipyridine (4,4-bipy) and 1,2-bis(4-pyridyl)ethane (bpe). Four compounds have been obtained as single crystals: 1D cationic coordination polymers [M(4,4-bipy)(OH2)4]2+ with chelidonate anions and water molecules in the second coordination sphere in 1∞[Zn(4,4-bipy)(H2O)4]chel·3H2O (2) and in the two pseudopolymorphic 1∞[Cu(4,4-bipy)(H2O)4]chel·nH2O (n = 3, 4a; n = 6, 4b), and the 2D neutral coordination polymers 2∞[Zn(chel)(4,4-bipy)(H2O)]·2H2O (1) and 2∞[Zn(chel)(bpe)(H2O)]·H2O (3) where the chelidonate anion acts as a bridging ligand. The effects of the hydrogen bonds on the crystal packing were analyzed. The role of the water molecules hosted within the crystals lattices was also studied.Ministerio de Ciencia e Innovación | Ref. PID2019-110218RB-I0

Polysaccharide-based hydrogels for the controlled delivery of therapeutic biomacromolecules

In the last decade, polysaccharide hydrogels have been extensively used in the development of novel drug delivery systems. Their excellent biocompatible and biodegradation characteristics as well as their green origin make them an appealing resource for their implementation. In this chapter, we sum up various polysaccharide hydrogels of diverse nature, combined or not with other polymers or drug delivery systems, implemented in the delivery of biotherapeutics as proteins, growth factors, gene vector, enzymes, hormones or monoclonal antibodies, with a special focus on pharmaceutical and biotechnological fields.publishe

Bioinspired superamphiphobic surfaces as a tool for polymer-and solvent-independent preparation of drug-loaded spherical particles

Superamphiphobic surfaces were evaluated as a tool to prepare spherical particles from polymers and solvents of very diverse nature, under mild conditions and with 100% drug encapsulation yield. Different from bioinspired superhydrophobic surfaces suitable only for aqueous dispersions, the superamphiphobic platforms allowed the formation of spherical droplets when solvents of any polarity were deposited onto them. Spherical poly(d,l-lactide-co-glycolide) (PLGA) particles were synthesized by placing drops of PLGA/ciprofloxacin suspensions in dioxane on a superamphiphobic surface followed by solvent evaporation. The particles prepared covering a wide range of PLGA/ciprofloxacin weight ratios delivered a 20% dose in the first 24h and then sustained the release of the remaining drug for more than 1month. The particles, both freshly prepared and after being 26days in the release medium, showed efficiency against different types of microorganisms. The developed polymer- and solvent-independent approach could be useful for microencapsulation with very high efficiency of active substances of varied nature into size-tunable particles for a wide range of applications in an affordable and cost-effective manner.This work was supported by Fundacao para a Ciencia e Tecnologia (FCT) through project PTDC/CTM-BIO/1814/2012, Spanish Ministerio de Economia y Competitividad (SAF 2011-22771; PRI-AIBPT-2011-1211), Xunta de Galicia (CN 2012/045) and FEDER. The authors thank Beatriz Magarinos for help with the microbiological experiments