Shape transformations of lipid vesicles by insertion of bulky-head lipids

Lipid vesicles, in particular Giant Unilamellar Vesicles (GUVs), have been increasingly important as compartments of artificial cells to reconstruct living cell-like systems in a bottom-up fashion. Here, we report shape transformations of lipid vesicles induced by polyethylene glycol-lipid conjugate (PEG lipids). Statistical analysis of deformed vesicle shapes revealed that shapes vesicles tend to deform into depended on the concentration of the PEG lipids. When compared with theoretically simulated vesicle shapes, those shapes were found to be more energetically favorable, with lower membrane bending energies than other shapes. This result suggests that the vesicle shape transformations can be controlled by externally added membrane molecules, which can serve as a potential method to control the replications of artificial cells

Application of Polyethylene Glycol to Promote Cellular Biocompatibility of Polyhydroxybutyrate Films

Polyhydroxybutyrate (PHB) is a biomaterial with potential for applications in biomedical and tissue engineering; however, its brittle nature and high crystallinity limit its potential. Blending PHB with a variety of PEGs produced natural-synthetic composite films composed of FDA-approved polymers with significant reductions in crystallinity, from 70.1% for PHB films to 41.5% for its composite with a 30% (w/w) loading of PEG2000. Blending also enabled manipulation of the material properties, increasing film flexibility with an extension to break of 2.49±1.01% for PHB films and 8.32±1.06% for films containing 30% (w/w) PEG106. Significant changes in the film surface properties, as measured by porosity, contact angles, and water uptake, were also determined as a consequence of the blending process, and these supported greater adhesion and proliferation of neural-associated olfactory ensheathing cells (OECs). A growth rate of 7.2×105 cells per day for PHB films with 30% (w/w) PEG2000 loading compared to 2.5×105 for PHB films was observed. Furthermore, while cytotoxicity of the films as measured by lactate dehydrogenase release was unaffected, biocompatibility, as measured by mitochondrial activity, was found to increase. It is anticipated that fine control of PEG composition in PHB-based composite biomaterials can be utilised to support their applications in medicinal and tissue engineering applications. Copyright © 2011 Rodman T. H. Chan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Safety of COVID-19 vaccines administered in the EU: Should we be concerned?

The COVID-19 pandemic has had an unprecedented and devastating impact on public health, society and economics around the world. As a result, the development of vaccines to protect individuals from symptomatic COVID-19 infections has represented the only feasible health tool to combat the spread of the disease. However, at the same time the development and regulatory assessment of different vaccines has challenged pharmaceutical industries and regulatory agencies as this process has occurred in the shorter time ever though. So far, two mRNA and two adenovirus-vectored vaccines have received a conditional marketing authorisation in the EU and other countries. This review summarized and discusses the assessment reports of the European Medicine Agency (EMA) concerning the safety of the 3 vaccines currently used in the EU (Pfizer, Moderna and Astra-Zeneca). A particular focus has been paid to safety information from pre-clinical (animal) and clinical (phase 3 trials) studies. Overall, the most frequent adverse effects reported after the administration of these vaccines consisted of local reactions at the injection site (sore arm and erythema) followed by non-specific systemic effects (myalgia, chills, fatigue, headache, and fever), which occurred soon after vaccination and resolved shortly. Rare cases of vaccine-induced immune thrombotic thrombocytopenia have been reported for Vaxzevria. Data on long-term studies, interaction with other vaccines, use in pregnancy/breast-feeding, use in immunocompromised subjects, and in subjects with comorbidities, autoimmune or inflammatory disorders are still missing for these vaccines. Therefore, careful follow-up and surveillance studies for continued vaccine safety monitoring will be needed to ascertain the potential risks of such adverse events or diseases. In conclusion, the benefits and risks of current COVID-19 vaccines must be weighed against the real possibility of contract the disease and develop complications and long-term sequels; all this on the basis of the available scientific evidence and in the absence of unmotivated biases

Self-Assembled Lipid Nanomedicines for siRNA Tumor Targeting

Lipid-based nanoparticle technology has developed from chemical drug carrier into an efficient multifunctional siRNA tumor targeting delivery system. In this review, we start with an overview of the lipid-based nanomedicine history and the two classes of lipidic vectors for DNA or siRNA delivery. Then we discuss the features of lipid-based nanomedicine that lead to effective tumor targeting and the principles behind. We also discuss nanoparticle surface modification, classes of tumor targeting ligands, and other state-of-the-art strategies for enhancing endosome release primarily focused on lipid-based systems. At the end, we show that multifunctional self-assembled lipid-based nanoparticles could also be versatile delivery vehicles for cancer molecular imaging probes

Design and Synthesis of Antithrombotic Liposomal Protein Conjugate

Recent advances in the molecular bases of haemostasis have highlighted that endothelial thrombomodulin (TM) plays a critical role in local haemostasis by binding thrombin and subsequently converting protein C to its active form (APC). In addition, the binding of thrombin to TM drastically alters the thrombin\u27s procoagulant activities to anticoagulant activities. The lipid bilayer in which it resides serves as an essential \u27cofactor\u27, locally concentrating and coordinating the appropriate alignment of reacting cofactors and substrates for protein C activation. On the other hand, liposomes have been extensively studied as cell membrane model as well as carrier for delivering certain vaccines, enzymes, drugs, or genes. In this study, antithrombotic liposomal TM conjugate was design and developed by combination of antithrombotic membrane protein TM into liposome through recombinant and bioorthogonal conjugation techniques, which providing a rational strategy for generating novel and potential antithrombotic agent. Namely, the liposomal TM conjugate mimics the native endothelial antithrombotic mechanism of both TM and lipid components and thus is more forceful than current antithrombotic agent.First, an efficient and chemoselective liposome surface functionalization method was developed based on Staudinger ligation, in which a model compound carbohydrate derivative carrying a spacer with azide was conjugated onto the surface of preformed liposomes carrying a terminal triphenylosphine in PBS buffer (pH 7.4) and at room temperature.Second, recombinant TM containing the EGF-like domains 456 with an azidohomoalaine at the C-terminal has been expressed and incorporated into liposome to form antithrombotic liposomal TM conjugate via Staudinger ligation. In addition, another chemically selective liposomal surface functionalization method for antithrombotic liposomal TM conjugated has been developed based on copper-free click chemistry, which provides an alternative approach to improving reaction efficiency and stability an

Design and Synthesis of Antithrombotic Liposomal Protein Conjugate

Recent advances in the molecular bases of haemostasis have highlighted that endothelial thrombomodulin (TM) plays a critical role in local haemostasis by binding thrombin and subsequently converting protein C to its active form (APC). In addition, the binding of thrombin to TM drastically alters the thrombin\u27s procoagulant activities to anticoagulant activities. The lipid bilayer in which it resides serves as an essential \u27cofactor\u27, locally concentrating and coordinating the appropriate alignment of reacting cofactors and substrates for protein C activation. On the other hand, liposomes have been extensively studied as cell membrane model as well as carrier for delivering certain vaccines, enzymes, drugs, or genes. In this study, antithrombotic liposomal TM conjugate was design and developed by combination of antithrombotic membrane protein TM into liposome through recombinant and bioorthogonal conjugation techniques, which providing a rational strategy for generating novel and potential antithrombotic agent. Namely, the liposomal TM conjugate mimics the native endothelial antithrombotic mechanism of both TM and lipid components and thus is more forceful than current antithrombotic agent.First, an efficient and chemoselective liposome surface functionalization method was developed based on Staudinger ligation, in which a model compound carbohydrate derivative carrying a spacer with azide was conjugated onto the surface of preformed liposomes carrying a terminal triphenylosphine in PBS buffer (pH 7.4) and at room temperature.Second, recombinant TM containing the EGF-like domains 456 with an azidohomoalaine at the C-terminal has been expressed and incorporated into liposome to form antithrombotic liposomal TM conjugate via Staudinger ligation. In addition, another chemically selective liposomal surface functionalization method for antithrombotic liposomal TM conjugated has been developed based on copper-free click chemistry, which provides an alternative approach to improving reaction efficiency and stability an

Des aptamères pour améliorer l’encapsulation et la libération contrôlée des liposomes

Mémoire par articleHypothèse : L’incorporation dans des liposomes d’aptamères spécifiques à un principe actif permet d’obtenir une encapsulation active du principe actif et de modifier les profils de libération sans diminuer l’efficacité thérapeutique. Méthode : Une série d’aptamères d’affinité variable a été incorporée dans la préparation de liposomes cationiques. Ces lipoplexes ainsi formés ont été caractérisés en taille par diffusion dynamique de la lumière et par la mesure du potentiel de surface zêta. Ils ont été optimisés en matière de complexation maximale des aptamères, puis incubés avec la doxorubicine, choisie comme principe actif modèle. L’efficacité d’encapsulation de la doxorubicine a été comparée avec et sans aptamères, et contre la méthode d’encapsulation active offerte commercialement. Les meilleures formulations ont été étudiées sur le plan de la cinétique de libération et l’efficacité de celles-ci a été évaluée pour leur cytotoxicité sur des cellules cancéreuses de type HeLa. Résultats : Les vecteurs cationiques optimisés permettent la complexation d’au moins 94% des aptamères. Trois des quatre aptamères ont démontré de l’encapsulation active de la doxorubicine, avec des efficacités d’encapsulation allant jusqu’à 85%. De ces trois formulations, différents profils de libération ont été obtenus, permettant tous une libération plus importante qu’une formulation ressemblant aux liposomes commerciaux de doxorubicine (Doxil®). L’efficacité des trois formulations testées sur les cellules HeLa s'est avérée équivalente ou supérieure au standard similaire du Doxil®.Hypothesis : Incorporation in some liposomes of specific aptamers for a drug allowed the obtaining of active encapsulation of that drug and allowed the modification of their drug release profiles, without negatively impacting its therapeutic efficacy. Methods : A series of aptamers of various affinity were incorporated in the preparation of cationic liposomes. The resulting lipoplexes were characterized for their size by dynamic light scattering method and their surface potential were analysed by zeta potential measurement. Lipoplexes were optimized in terms of highest aptamer complexation and they were incubated with doxorubicin, a model drug that was chosen. The encapsulation efficiency of doxorubicin was compared with and without the presence of aptamers, and with the commercially available active loading method. The best formulations were studied for their doxorubicin’s release kinetic, with the different aptamers, and they were tested for their cytotoxicity on HeLa cancer cells. Results : Cationic liposomes were optimized to allow a minimum aptamer complexation of 94%. Three out of the four tested aptamers were able to demonstrate active loading capabilities, with up to 85% encapsulation efficiencies. Out of these three formulations, very different release profiles were found, all allowing more initial content release of the commercially-like available doxorubicin’s liposomes (Doxil®). The efficacy of those three formulations on HeLa cancer cells demonstrated equivalent or higher cytotoxicity than the similar standard of Doxil®

Exploring controlled drug release from magneto liposomes

Doctor of PhilosophyDepartment of ChemistryViktor ChikanThis thesis focuses on exploring fast and controlled drug release from several liposomal drug delivery systems including its underlying mechanics. In addition, the construction of a pulsed high-voltage rotating electromagnet is demonstrated based on a nested Helmholtz coil design. Although lots of different drug delivery mechanisms can be used, fast drug delivery is very important to utilize drug molecules that are short-lived under physiological conditions. Techniques that can release model molecules under physiological conditions could play an important role to discover the pharmacokinetics of short-lived substances in the body. In this thesis, an experimental method is developed for the fast release of the liposomes’ payload without a significant increase in (local) temperatures. This goal is achieved by using short magnetic pulses to disrupt the lipid bilayer of liposomes loaded with magnetic nanoparticles. This thesis also demonstrates that pulsed magnetic fields can generate ultrasound from colloidal superparamagnetic nanoparticles. Generating ultrasound remotely by means of magnetic fields is an important technological development to circumvent some of the drawbacks of the traditional means of ultrasound generation techniques. In this thesis, it is demonstrated that ultrasound is generated from colloidal superparamagnetic nanoparticles when exposed to pulsed and alternating magnetic fields. Furthermore, a comparison between inhomogeneous and homogeneous magnetic fields indicates that both homogeneous and inhomogeneous magnetic fields could be important for efficient ultrasound generation; however, the latter is more important for dilute colloidal dispersion of magnetic nanoparticles. In strong magnetic fields, the ultrasound generated from the colloidal magnetic nanoparticles shows reasonable agreement with the magnetostriction effect commonly observed for bulk ferromagnetic materials. At low magnetic fields, the colloidal magnetic nanoparticle dispersion produces considerable amount of ultrasound when exposed to a.c. magnetic fields in the 20−5000 kHz frequency range. It is expected that the ultrasound generated from magnetic nanoparticles will have applications toward the acoustic induction of bioeffects in cells and manipulating the permeability of biological membrane