Mucoadhesive gellan gum-based and carboxymethyl cellulose -based hydrogels containing gemcitabine and papain for bladder cancer treatment.

Local treatment of bladder cancer faces several limitations such as short residence time or low permeation through urothelium tissue. The aim of this work was to develop patient-friendly mucoadhesive gel formulations combining gemcitabine and the enzyme papain for improved intravesical chemotherapy delivery. Hydrogels based on two different polysaccharides, gellan gum and sodium carboxymethylcellulose (CMC), were prepared with either native papain or papain nanoparticles (nanopapain) to explore for the first time their use as permeability enhancers through bladder tissue. Gel formulations were characterized regarding enzyme stability, rheological behavior, retention on bladder tissue and bioadhesion, drug release properties, permeation capacity, and biocompatibility. After 90 days of storage, the enzyme loaded in the CMC gels retained up to 83.5 ± 4.9 % of its activity in the absence of the drug, and up to 78.1 ± 5.3 with gemcitabine. The gels were mucoadhesive and the enzyme papain showed mucolytic action, which resulted in resistance against washing off from the urothelium and enhanced permeability of gemcitabine in the ex vivo tissue diffusion tests. Native papain shortened lag-time tissue penetration to 0.6 h and enhanced 2-fold drug permeability All formulations demonstrated pseudoplastic behavior and no irritability. Overall, the developed formulations have potential as an upgraded alternative to intravesical therapy for bladder cancer treatment.

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.

Mucoadhesive Polymers and Their Applications in Drug Delivery Systems for the Treatment of Bladder Cancer.

Bladder cancer (BC) is the tenth most common type of cancer worldwide, affecting up to four times more men than women. Depending on the stage of the tumor, different therapy protocols are applied. Non-muscle-invasive cancer englobes around 70% of the cases and is usually treated using the transurethral resection of bladder tumor (TURBIT) followed by the instillation of chemotherapy or immunotherapy. However, due to bladder anatomy and physiology, current intravesical therapies present limitations concerning permeation and time of residence. Furthermore, they require several frequent catheter insertions with a reduced interval between doses, which is highly demotivating for the patient. This scenario has encouraged several pieces of research focusing on the development of drug delivery systems (DDS) to improve drug time residence, permeation capacity, and target release. In this review, the current situation of BC is described concerning the disease and available treatments, followed by a report on the main DDS developed in the past few years, focusing on those based on mucoadhesive polymers as a strategy. A brief review of methods to evaluate mucoadhesion properties is also presented; lastly, different polymers suitable for this application are discussed.

Preparation of Vancomycin-Loaded Aerogels Implementing Inkjet Printing and Superhydrophobic Surfaces.

Chronic wounds are physical traumas that significantly impair the quality of life of over 40 million patients worldwide. Aerogels are nanostructured dry porous materials that can act as carriers for the local delivery of bioactive compounds at the wound site. However, aerogels are usually obtained with low drug loading yields and poor particle size reproducibility and urges the implementation of novel and high-performance processing strategies. In this work, alginate aerogel particles loaded with vancomycin, an antibiotic used for the treatment of Staphylococcus aureus infections, were obtained through aerogel technology combined with gel inkjet printing and water-repellent surfaces. Alginate aerogel particles showed high porosity, large surface area, a well-defined spherical shape and a reproducible size (609 ± 37 µm). Aerogel formulation with vancomycin loadings of up to 33.01 ± 0.47 µg drug/mg of particle were obtained with sustained-release profiles from alginate aerogels for more than 7 days (PBS pH 7.4 medium). Overall, this novel green aerogel processing strategy allowed us to obtain nanostructured drug delivery systems with improved drug loading yields that can enhance the current antibacterial treatments for chronic wounds.

Recent Progress on Polysaccharide-Based Hydrogels for Controlled Delivery of Therapeutic Biomolecules.

A plethora of applications using polysaccharides have been developed in recent years due to their availability as well as their frequent nontoxicity and biodegradability. These polymers are usually obtained from renewable sources or are byproducts of industrial processes, thus, their use is collaborative in waste management and shows promise for an enhanced sustainable circular economy. Regarding the development of novel delivery systems for biotherapeutics, the potential of polysaccharides is attractive for the previously mentioned properties and also for the possibility of chemical modification of their structures, their ability to form matrixes of diverse architectures and mechanical properties, as well as for their ability to maintain bioactivity following incorporation of the biomolecules into the matrix. Biotherapeutics, such as proteins, growth factors, gene vectors, enzymes, hormones, DNA/RNA, and antibodies are currently in use as major therapeutics in a wide range of pathologies. In the present review, we summarize recent progress in the development of polysaccharide-based hydrogels of diverse nature, alone or in combination with other polymers or drug delivery systems, which have been implemented in the delivery of biotherapeutics in the pharmaceutical and biomedical fields.

Percutaneous ablation of obscure hypovascular liver tumours in challenging locations using arterial CT-portography guidance.

PURPOSE: The purpose of this study was to evaluate the feasibility, safety and efficacy of percutaneous ablation (PA) of obscure hypovascular liver tumors in challenging locations using arterial CT-portography (ACP) guidance. MATERIALS AND METHODS: A total of 26 patients with a total of 28 obscure, hypovascular malignant liver tumors were included. There were 18 men and 6 women with a mean age of 58±14 (SD) years (range: 37-75 years). The tumors had a mean diameter of 14±10 (SD) mm (range: 7-24mm) and were intrahepatic cholangiocarcinoma (4/28; 14%), liver metastases from colon cancer (18/28; 64%), corticosurrenaloma (3/28; 11%) or liver metastases from breast cancer (3/28; 11%). All tumors were in challenging locations including subcapsular (14/28; 50%), liver dome (9/28; 32%) or perihilar (5/28; 18%) locations. A total of 28 PA (12 radiofrequency ablations, 11 microwave ablations and 5 irreversible electroporations) procedures were performed under ACP guidance. RESULTS: A total of 67 needles [mean: 2.5±1.5 (SD); range: 1-5] were inserted under ACP guidance, with a 100% technical success rate for PA. Median total effective dose was 26.5 mSv (IQR: 19.1, 32.2 mSv). Two complications were encountered (pneumothorax; one abscess both with full recovery), yielding a complication rate of 7%. No significant change in mean creatinine clearance was observed (80.5mL/min at baseline and 85.3mL/min at day 7; P=0.8). Post-treatment evaluation of the ablation zone was overestimated on ACP compared with conventional CT examination in 3/28 tumors (11%). After a median follow-up of 20 months (range: 12-35 months), local tumor progression was observed in 2/28 tumours (7%). CONCLUSION: ACP guidance is feasible and allows safe and effective PA of obscure hypo-attenuating liver tumors in challenging locations without damaging the renal function and with acceptable radiation exposure. Post-treatment assessment should be performed using conventional CT or MRI to avoid size overestimation of the ablation zone.

Environmental Impact of Phosphogypsum-Derived Building Materials.

The aim of the present work was to characterize the products obtained from the treatment of phosphogypsum residue by means of two recovery routes, and also to evaluate the concentrations of heavy metals and radionuclides in the materials obtained and their leachates. In this way, it is possible to determine how the most hazardous components of phosphogypsum behave during procedures until their stabilization through CO2 fixation. This study provides an initial estimate of the possibilities of reusing the resulting products from a health and safety risk standpoint and their potential polluting capacity. The phases resulting from the transformations were controlled, and the behaviour of standard mortars manufactured from the resulting paste lime was studied. In all cases, an additional control of the leachate products was performed.

Intra arterial treatment of hepatocellular carcinoma: Comparison of MELD score variations between radio-embolization and chemo-embolization.

PURPOSE: The purpose of this study was to assess liver function deterioration, as assessed using the model for end-stage liver disease (MELD) score variations, following transarterial chemo-embolization (TACE) versus selective internal radiation therapy (SIRT) in patients with unresectable unilobar hepatocellular carcinomas (HCC). PATIENTS AND METHODS: We retrospectively evaluated all patients who underwent a single conventional TACE or SIRT procedure in our department from May 2013 to May 2018 for unilobar unresectable HCC. A total of 86 patients (76 men, 20 women; mean age, 65.5 years) were included. There were 63 patients in the TACE group [56 men, 7 women; mean age, 65.1±9.6 (SD) years] and 23 patients in the SIRT group [20 men, 3 women; mean age, 70±9.2 (SD) years]. Delta MELD, defined as post treatment minus pre-treatment MELD score, was considered for liver function deterioration and compared between patients who underwent single lobar treatment of SIRT versus TACE. RESULTS: Patients in SIRT group had significant higher tumor burden, alpha-fetoprotein serum level, and rates of macroscopic vessel invasion. Mean pre-treatment MELD scores did not differ between TACE [mean, 8.41±1.71 (SD); range: 7.24-9.24] and SIRT groups [mean, 8.36±1.74 (SD); range: 7.07-9.21] (P=0.896) as well as Child-Pugh class and albumin-bilirubin (ALBI) grade distribution. However, following treatment, mean DeltaMELD was greater in TACE group (mean, 0.83±1.83 [SD]; range: -0.30--1.31) than in SIRT group (mean, -0.13±1.06 [SD]; range: -0.49-0.32) (P=0.021). At multivariate analysis, SIRT treatment was independently associated with a lower DeltaMELD score than TACE (R=-0.955 [-1.68; -0.406]; P=0.017;). CONCLUSION: Whereas performed in patients with higher tumor burden, SIRT resulted in lower degrees of liver function worsening as assessed using MELD score variations.

Direct, indirect and total effectiveness of bivalent HPV vaccine in women in Galicia, Spain.

Bivalent human papillomavirus (HPV) vaccine was incorporated into the childhood vaccination calendar in Galicia, Spain in 2008. The objectives of this study were to estimate direct, indirect and total effectiveness of HPV vaccine and to identify sexual habits changes in the post-vaccination period in Galicia, Spain.Endocervical scrapings of 745 women attending 7 Health Areas of the Galician Public Health Service were collected in the post-vaccination period, from 2014-2017. Two groups were studied: women born between 1989 and 1993 (n = 397) and women born in 1994 or later (n = 348). Twelve high-risk human papillomavirus (HR-HPV) genotypes were detected by Cobas® 4800 HPV test (Roche Diagnostics, Mannheim, Germany). The Linear Array® HPV Genotyping Test (Roche Diagnostics) was used for HR-HPV genotype detection other than HPV 16/18. Information about sexual habits was collected by a self-filled questionnaire. Post-vaccination data were compared to previously published pre-vaccination data obtained between 2008 and 2010 in Galicia from women of the same age (18-26 years old, n = 523). The Stata 14.2 software was employed for statistical analyses.Data from 392 unvaccinated and 353 vaccinated women were compared. For unvaccinated and vaccinated women, HPV 16/18 prevalence was 9.2% and 0.8%, respectively, and HPV 31/33/45 prevalence was 8.4% and 1.1%, respectively. Direct, indirect and total effectiveness of the HPV vaccine were (%, 95% CI): 94 (72-99), 30 (-11-56) and 95 (79-99), respectively, for HPV 16/18 and 83 (46-94), -10 (-88-33) and 84 (54-94), respectively, for HPV 31/33/45. The number of women with first intercourse before 17 years old and 3 or more sexual partners along life was higher in the post-vaccination period (p < 0.05). A positive impact of bivalent HPV vaccine was observed, both on direct and cross protection. Sexual habits could have changed in the post-vaccination period.

Highly dense linkage maps from 31 full-sibling families of turbot (Scophthalmus maximus) provide insights into recombination patterns and chromosome rearrangements throughout a newly refined genome assembly.

Highly dense linkage maps enable positioning thousands of landmarks useful for anchoring the whole genome and for analysing genome properties. Turbot is the most important cultured flatfish worldwide and breeding programs in the fifth generation of selection are targeted to improve growth rate, obtain disease resistant broodstock and understand sex determination to control sex ratio. Using a Restriction-site Associated DNA approach, we genotyped 18,214 single nucleotide polymorphism in 1,268 turbot individuals from 31 full-sibling families. Individual linkage maps were combined to obtain a male, female and species consensus maps. The turbot consensus map contained 11,845 markers distributed across 22 linkage groups representing a total normalised length of 3,753.9 cM. The turbot genome was anchored to this map, and scaffolds representing 96% of the assembly were ordered and oriented to obtain the expected 22 megascaffolds according to its karyotype. Recombination rate was lower in males, especially around centromeres, and pairwise comparison of 44 individual maps suggested chromosome polymorphism at specific genomic regions. Genome comparison across flatfish provided new evidence on karyotype reorganisations occurring across the evolution of this fish group.

Performance and precision of double digestion RAD (ddRAD) genotyping in large multiplexed datasets of marine fish species.

The development of Genotyping-By-Sequencing (GBS) technologies enables cost-effective analysis of large numbers of Single Nucleotide Polymorphisms (SNPs), especially in "non-model" species. Nevertheless, as such technologies enter a mature phase, biases and errors inherent to GBS are becoming evident. Here, we evaluated the performance of double digest Restriction enzyme Associated DNA (ddRAD) sequencing in SNP genotyping studies including high number of samples. Datasets of sequence data were generated from three marine teleost species (>5500 samples, >2.5 × 1012 bases in total), using a standardized protocol. A common bioinformatics pipeline based on STACKS was established, with and without the use of a reference genome. We performed analyses throughout the production and analysis of ddRAD data in order to explore (i) the loss of information due to heterogeneous raw read number across samples; (ii) the discrepancy between expected and observed tag length and coverage; (iii) the performances of reference based vs. de novo approaches; (iv) the sources of potential genotyping errors of the library preparation/bioinformatics protocol, by comparing technical replicates. Our results showed use of a reference genome and a posteriori genotype correction improved genotyping precision. Individual read coverage was a key variable for reproducibility; variance in sequencing depth between loci in the same individual was also identified as an important factor and found to correlate to tag length. A comparison of downstream analysis carried out with ddRAD vs single SNP allele specific assay genotypes provided information about the levels of genotyping imprecision that can have a significant impact on allele frequency estimations and population assignment. The results and insights presented here will help to select and improve approaches to the analysis of large datasets based on RAD-like methodologies.

Evolution and conservation of Characidium sex chromosomes.

Fish species exhibit substantial variation in the degree of genetic differentiation between sex chromosome pairs, and therefore offer the opportunity to study the full range of sex chromosome evolution. We used restriction-site associated DNA sequencing (RAD-seq) to study the sex chromosomes of Characidium gomesi, a species with conspicuous heteromorphic ZW/ZZ sex chromosomes. We screened 9863 single-nucleotide polymorphisms (SNPs), corresponding to ~1 marker/100 kb distributed across the genome for sex-linked variation. With this data set, we identified 26 female-specific RAD loci, putatively located on the W chromosome, as well as 148 sex-associated SNPs showing significant differentiation (average FST=0.144) between males and females, and therefore in regions of more recent divergence between the Z and W chromosomes. In addition, we detected 25 RAD loci showing extreme heterozygote deficiency in females but which were in Hardy-Weinberg equilibrium in males, consistent with degeneration of the W chromosome and therefore female hemizygosity. We validated seven female-specific and two sex-associated markers in a larger sample of C. gomesi, of which three localised to the W chromosome, thereby providing useful markers for sexing wild samples. Validated markers were evaluated in other populations and species of the genus Characidium, this exploration suggesting a rapid turnover of W-specific repetitive elements. Together, our analyses point to a complex origin for the sex chromosome of C. gomesi and highlight the utility of RAD-seq for studying the composition and evolution of sex chromosomes systems in wild populations.

Flue gas adsorption by single-wall carbon nanotubes: A Monte Carlo study.

Adsorption of flue gases by single-wall carbon nanotubes (SWCNT) has been studied by means of Monte Carlo simulations. The flue gas is modeled as a ternary mixture of N2, CO2, and O2, emulating realistic compositions of the emissions from power plants. The adsorbed flue gas is in equilibrium with a bulk gas characterized by temperature T, pressure p, and mixture composition. We have considered different SWCNTs with different chiralities and diameters in a range between 7 and 20 Å. Our results show that the CO2 adsorption properties depend mainly on the bulk flue gas thermodynamic conditions and the SWCNT diameter. Narrow SWCNTs with diameter around 7 Å show high CO2 adsorption capacity and selectivity, but they decrease abruptly as the SWCNT diameter is increased. For wide SWCNT, CO2 adsorption capacity and selectivity, much smaller in value than for the narrow case, decrease mildly with the SWCNT diameter. In the intermediate range of SWCNT diameters, the CO2 adsorption properties may show a peculiar behavior, which depend strongly on the bulk flue gas conditions. Thus, for high bulk CO2 concentrations and low temperatures, the CO2 adsorption capacity remains high in a wide range of SWCNT diameters, although the corresponding selectivity is moderate. We correlate these findings with the microscopic structure of the adsorbed gas inside the SWCNTs.

Hormonal changes and follicular activity after treatment with intravaginal progesterone-releasing devices in llamas.

Plasma progesterone (P4 ) concentrations and follicular activity after administration of different P4 doses were evaluated in 33 adult female llamas treated with intravaginal devices. In Study 1, a group of llamas (n = 10) was treated with an intravaginal device (IVD) containing 160 (n = 5) or 780 mg of P4 (n = 5). Based on the results from the first study, in Study 2, females with follicles at different stages of development were treated with the IVD containing 780 mg of P4 (n = 21) or remain untreated (control; n = 12) to evaluate the effect of P4 on follicular activity. In Study 1, the IVD containing 160 mg of P4 induced follicular turnover in 60% of females while the remaining 40% of llamas developed persistent follicles. Thus, this device controlled follicular activity in llamas, although it promotes the persistence of follicles present at start of treatment. Conversely, in both studies, the IVD containing 780 mg of P4 suppressed follicular development and hasten the emergence of a new follicular wave in all females regardless of the follicular phase at insertion. Additionally, in Study 2, this device effectively concentrated the appearance of follicles with ovulatory diameter at a definite time after treatment in comparison with control animals. In conclusion, treatment with an IVD containing 780 mg of P4 would be considered for the control of follicular activity in llamas as it ensures the presence of a young follicle with ovulatory diameter by day 6 after the end of treatment in all females.

Childhood Poverty and Cognitive Development in Latin America in the 21st Century.

For at least eight decades, researchers have analyzed the association between childhood poverty and cognitive development in different societies worldwide, but few of such studies have been carried out in Latin America. The aim of the present paper is to systematically review the empirical studies that have analyzed the associations between poverty and cognitive development in children under 18 years of age from Latin American and Caribbean countries between 2000 and 2015. This analysis takes into consideration the country where the work was conducted, the experimental and analytical design, sample size and composition, cognitive and poverty paradigms implemented, levels of analysis, and the inclusion of mediation analyses. Through these, we identify common patterns in the negative impact of poverty that have been repeatedly verified in the literature in other continents; we also call attention to a set of issues regarding sample, design, paradigms, impact, and mediation analyses that should be considered in future studies in the region.

Magnetic Surfactants and Polymers with Gadolinium Counterions for Protein Separations.

New magnetic surfactants, (cationic hexadecyltrimethlyammonium bromotrichlorogadolinate (CTAG), decyltrimethylammonium bromotrichlorogadolinate (DTAG), and a magnetic polymer (poly(3-acrylamidopropyl)trimethylammonium tetrachlorogadolinate (APTAG)) have been synthesized by the simple mixing of the corresponding surfactants and polymer with gadolinium metal ions. A magnetic anionic surfactant, gadolinium tri(1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate) (Gd(AOT)3), was synthesized via metathesis. Both routes enable facile preparation of magnetically responsive magnetic polymers and surfactants without the need to rely on nanocomposites or organic frameworks with polyradicals. Electrical conductivity, surface tensiometry, SQUID magnetometry, and small-angle neutron scattering (SANS) demonstrate surface activity and self-aggregation behavior of the magnetic surfactants similar to their magnetically inert parent analogues but with added magnetic properties. The binding of the magnetic surfactants to proteins enables efficient separations under low-strength (0.33 T) magnetic fields in a new, nanoparticle-free approach to magnetophoretic protein separations and extractions. Importantly, the toxicity of the magnetic surfactants and polymers is, in some cases, lower than that of their halide analogues.

Microemulsions for Colorectal Cancer Treatments. General Considerations and Formulation of Methotrexate.

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-1000, 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.

Metazoan parasites of blue jack mackerel Trachurus picturatus (Perciformes: Carangidae) from Portuguese mainland waters.

Blue jack mackerel, Trachurus picturatus, is a carangid fish which constitutes an important commercial resource in the north-east Atlantic. Its metazoan parasite community from Portuguese mainland waters was investigated here for the first time. Nine parasite taxa were found, most of which are common parasites of Trachurus spp. The parasite community was broadly similar to that of the Atlantic horse mackerel, T. trachurus, from the same region, but two digenean species were detected in blue jack mackerel, Monascus filiformis and Tergestia sp., which did not occur in horse mackerel from this region. A comparison with the two previous studies of T. picturatus parasite communities shows that continental-shelf regions are characterized by higher prevalences of digenean trematodes and an absence of trypanorhynch cestodes, in contrast with oceanic regions.

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.

Interaction of poloxamine block copolymers with lipid membranes: Role of copolymer structure and membrane cholesterol content.

Interactions of X-shaped poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) block copolymers with cell membranes were investigated recording the π-A isotherms of monolayer systems of dipalmitoylphosphatidylcholine (DPPC):cholesterol 100:0; 80:20 and 60:40 mol ratio and evaluating the capability of the copolymers to trigger haemolysis or to protect from haemolytic agents. Four varieties of poloxamine (Tetronic 904, 908, 1107 and 1307) were chosen in order to cover a wide range of EO and PO units contents and molecular weights, and compared to a variety of poloxamer (Pluronic P85). The π-A isotherms revealed that the greater the content in cholesterol, the stronger the interaction of the block copolymers with the lipids monolayer. The interactions were particularly relevant at low pressures and low lipid proportions, mimicking the conditions of damaged membranes. Relatively hydrophobic copolymers bearing short PEO blocks (e.g., T904 and P85) intercalated among the lipids expanding the surface area (ΔGexc) but not effectively sealing the pores. These varieties showed haemolytic behavior. Oppositely, highly hydrophilic copolymers bearing long PEO blocks (e.g., T908, T1107 and T1307) caused membrane contraction and outer leaflet sealing due to strong interactions of PEO with cholesterol and diamine core with phospholipids. These later varieties were not haemolytic and exerted a certain protective effect against spontaneous haemolysis for both intact erythrocytes and cholesterol-depleted erythrocytes.