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Cervical cancer is one of the most common cancers affecting women worldwide. There are an estimated 570.000 new cases of cervical cancer each year and conventional treatments can cause severe side effects. In this work, we developed a platform for vaginal administration of lipophilic drugs for cervical cancer treatment. We formulated mucoadhesive cubosomes for the delivery of curcumin, a lipophilic drug for cervical cancer treatment, to increase its bioavailability and local absorption. This study tests the use of cubosomes for vaginal drug administration and assesses their potential efficiency using the CAM (chick embryo chorioallantoic membrane) model. SAXS (small-angle X-ray scattering), cryo-TEM (cryo-transmission electron microscopy), and dynamic light scattering (DLS) were employed to characterise the system. With ex vivo permeation and retention studies, we find that the curcumin released from our system is retained in the vaginal mucosa. In vitro cytotoxicity assay and cellular uptake showed an increased cytotoxic effect of curcumin against HeLa cell line when incorporated into the cubosomes. The curcumin-loaded cubosomes also demonstrated an antiangiogenic effect evaluated in vivo by the CAM model., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Realising the carbon (C) sequestration capacity of agricultural soils is needed to reach Paris Climate Agreement goals; thus, quantifying hedgerow planting potential to offset anthropogenic CO 2 emissions is crucial for accurate climate mitigation modelling. Although being a widespread habitat in England and throughout Europe, the potential of hedgerows to contribute to net-zero targets is unclear. This is the first study to quantify the soil organic carbon (SOC) sequestration rate associated with planting hedgerows. We derived SOC stocks beneath hedgerows based on two estimation methods to assess differences from adjacent intensively managed grassland fields and how these may be affected by sampling depth and hedgerow age, as well as the SOC estimation method used. Twenty-six hedgerows on five dairy farms in Cumbria, England, were classified based on the time since their planting. We measured SOC stocks in 10 cm depth intervals in the top 50 cm of soil beneath hedgerows and in adjacent grassland fields. SOC beneath hedgerows was on average 31.3% higher than in the fields, 3.3% for 2-4 year old hedgerows, 14.4% for 10 year old, 45.2% for 37 year old, and 57.2% for older ones. We show that SOC sequestration rate beneath 37 year old hedgerows was 1.48 Mg C ha -1  yr -1 in the top 50 cm of soil. If England reaches its goal of a 40% increase in hedgerow length, 6.3 Tg CO 2 will be stored in the soil over 40 years, annually offsetting 4.7%-6.4% of present-day agricultural CO 2 emissions. However, the current rate of planting funded by agri-environment schemes, which today reaches only 0.02% of emissions, is too slow. Private-sector payments for ecosystem services initiatives (e.g., 'Milk Plan') show much higher rates of planting and are needed alongside agri-environment schemes to ensure hedgerow planting contributes to net-zero targets., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lyotropic liquid crystalline nanoparticles with bicontinuous cubic internal nanostructure, known as cubosomes, have been proposed as nanocarriers in various medical applications. However, as these nanoparticles show a certain degree of cytotoxicity, particularly against erythrocytes, their application in systemic administrations is limited to date. Intending to produce a more biocompatible formulation, we prepared cubosomes for the first time stabilized with a biodegradable polyphosphoester-analog of the commonly used Pluronic F127. The ABA-triblock copolymer poly(methyl ethylene phosphate)-block-poly(propylene oxide)-block-poly(methyl ethylene phosphate) (PMEP-b-PPO-b-PMEP) was prepared by organocatalyzed ring-opening polymerization of MEP. The cytotoxic features of the resulting formulation were investigated against two different cell lines (HEK-293 and HUVEC) and human red blood cells. The response of the complement system was also evaluated. Results proved the poly(phosphoester)-based formulation was significantly less toxic than that prepared using Pluronic F127 with respect to all the tested cell lines and, more importantly, hemolysis assay and complement system activation tests demonstrated its very high hemocompatibility. The potentially biodegradable poly(phosphoester)-based cubosomes represent a new and versatile platform for preparation of functional and smart nanocarriers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Despite the advances in the treatment of rheumatoid arthritis (RA) achieved in the last few years, several patients are diagnosed late, do not respond to or have to stop therapy because of inefficacy and/or toxicity, leaving still a huge unmet need. Tissue-specific strategies have the potential to address some of these issues. The aim of the study is the development of a safe nanotechnology approach for tissue-specific delivery of drugs and diagnostic probes. CD34  +  endothelial precursors were addressed in inflamed synovium using targeted biodegradable nanoparticles (tBNPs). These nanostructures were made of poly-lactic acid, poly-caprolactone, and PEG and then coated with a synovial homing peptide. Immunofluorescence analysis clearly demonstrated their capacity to selectively address CD34  +  endothelial cells in synovial tissue obtained from human, mouse, and rat. Biodistribution studies in two different animal models of rheumatoid arthritis (antigen-induced arthritis/AIA and collagen-induced arthritis/CIA) confirmed the selective accumulation in inflamed joints but also evidenced the capacity of tBNP to detect early phases of the disease and the preferential liver elimination. The therapeutic effect of methotrexate (MTX)-loaded tBNPs were studied in comparison with conventional MTX doses. MTX-loaded tBNPs prevented and treated CIA and AIA at a lower dose and reduced administration frequency than MTX. Moreover, MTX-loaded tBNP showed a novel mechanism of action, in which the particles target and kill CD34  +  endothelial progenitors, preventing neo-angiogenesis and, consequently, synovial inflammation. tBNPs represent a stable and safe platform to develop highly-sensitive imaging and therapeutic approaches in RA targeting specifically synovial neo-angiogenesis to reduce local inflammation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)