Polypiperazine-Based Micelles of Mixed Composition for Gene Delivery.

We introduce a novel concept in nucleic acid delivery based on the use of mixed polymeric micelles (MPMs) as platforms for the preparation of micelleplexes with DNA. MPMs were prepared by the co-assembly of a cationic copolymer, poly(1-(4-methylpiperazin-1-yl)-propenone)-b-poly(d,l-lactide), and nonionic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) block copolymers. We hypothesize that by introducing nonionic entities incorporated into the mixed co-assembled structures, the mode and strength of DNA binding and DNA accessibility and release could be modulated.

Investigation of the Aggregation of Aβ Peptide (1-40) in the Presence of κ-Carrageenan-Stabilised Liposomes Loaded with Homotaurine.

The kinetics of amyloid aggregation was studied indirectly by monitoring the changes in the polydispersity of mixed dispersion of amyloid β peptide (1-40) and composite liposomes. The liposomes were prepared from the 1,2-dioleoyl-sn-glicero-3-phoshocholine (DOPC) phospholipid and stabilised by the electrostatic adsorption of κ-carrageenan. The produced homotaurine-loaded and unloaded liposomes had a highly negative electrokinetic potential and remarkable stability in phosphate buffer (pH 4 and 7.

Polycarbonate-Based Copolymer Micelles as Biodegradable Carriers of Anticancer Podophyllotoxin or Juniper Extracts.

Podophyllotoxin (PPT) is used in the industrial production of efficient anticancer, antiviral and other drugs. or are natural sources of PPT, but at present they are considered as endangered species. Their PPT content is variable, depending on the growing conditions.

Solvent-Free Synthesis of Multifunctional Block Copolymer and Formation of DNA and Drug Nanocarriers.

The synthesis of well-defined multifunctional polymers is of great importance for the development of complex materials for biomedical applications. In the current work, novel and multi-amino-functional diblock copolymer for potential gene and drug delivery applications was successfully synthesized. A highly efficient one-step and quantitative modification of an alkyne-functional polycarbonate-based precursor was performed, yielding double hydrophilic block copolymer with densely grafted primary amine side groups.

Remdesivir-Loaded Nanoliposomes Stabilized by Chitosan/Hyaluronic Acid Film with a Potential Application in the Treatment of Coronavirus Infection.

An object of the present study was the development of liposomes loaded with the medicine Veklury (remdesivir) stabilized by electrostatic adsorption of polysaccharide film formed from chitosans with different physicochemical characteristics and hyaluronic acid. The functionalization of the structures was achieved through the inclusion of an aptamer (oligonucleotide sequence) with specific affinity to the spike protein of the human coronavirus HCoV-OC43. The hydrodynamic size, electrokinetic potential and stability of the structures were evaluated at each step in the procedure.

Green Synthesis and the Evaluation of a Functional Amphiphilic Block Copolymer as a Micellar Curcumin Delivery System.

Polymer micelles represent one of the most attractive drug delivery systems due to their design flexibility based on a variety of macromolecular synthetic methods. The environmentally safe chemistry in which the use or generation of hazardous materials is minimized has an increasing impact on polymer-based drug delivery nanosystems. In this work, a solvent-free green synthetic procedure was applied for the preparation of an amphiphilic diblock copolymer consisting of biodegradable hydrophobic poly(acetylene-functional carbonate) and biocompatible hydrophilic polyethylene glycol (PEG) blocks.

Flexible Polymer-Ionic Liquid Films for Supercapacitor Applications.

Mechanically and thermally stable novel gel polymer electrolytes (GPEs) have been prepared and applied in supercapacitor cells. Quasi-solid and flexible films were prepared by solution casting technique and formulated by immobilization of ionic liquids (ILs) differing in their aggregate state. A crosslinking agent and a radical initiator were added to further stabilize them.

Nanoarchitectonics of Spherical Nucleic Acids with Biodegradable Polymer Cores: Synthesis and Evaluation.

Spherical nucleic acids (SNAs) have gained significant attention due to their unique properties allowing them to overcome the challenges that face current nanocarriers used for gene therapies. The aim of this study is to synthesize and characterize polymer-oligonucleotide conjugates of different architecture and to evaluate the possibility of forming SNAs with biodegradable cores. Initially, two types of azide (multi)functional polyester-based (co)polymers were successfully synthesized and characterized.

Point-of-Care Ultrasound to Detect Acute Large Vessel Occlusions in Stroke Patients: A Proof-of-Concept Study.

Background And Purpose: A primary admission of patients with suspected acute ischemic stroke and large vessel occlusion (LVO) to centers capable of providing endovascular stroke therapy (EVT) may induce shorter time to treatment and better functional outcomes. One of the limitations in this strategy is the need for accurately identifying LVO patients in the prehospital setting. We aimed to study the feasibility and diagnostic performance of point-of-care ultrasound (POCUS) for the detection of LVO in patients with acute stroke.

Functional Polyion Complex Micelles for Potential Targeted Hydrophobic Drug Delivery.

Polyion complex (PIC) micelles have gained an increasing interest, mainly as promising nano-vehicles for the delivery of various hydrophilic charged (macro)molecules such as DNA or drugs to the body. The aim of the present study is to construct novel functional PIC micelles bearing cell targeting ligands on the surface and to evaluate the possibility of a hydrophobic drug encapsulation. Initially, a pair of functional oppositely charged peptide-based hybrid diblock copolymers were synthesized and characterized.

Triblock Copolymer Micelles with Tunable Surface Charge as Drug Nanocarriers: Synthesis and Physico-Chemical Characterization.

Polymeric micelles have gained increasing interest as efficient drug delivery systems for cancer treatment and diagnosis. The aim of the present study was to construct and to evaluate novel polymeric nanosized drug carriers with tunable surface charges. Initially, amphiphilic triblock copolymers with predetermined molar mass characteristics were synthesized by applying controlled polymerization techniques.

Functional Polyglycidol-Based Block Copolymers for DNA Complexation.

Gene therapy is an attractive therapeutic method for the treatment of genetic disorders for which the efficient delivery of nucleic acids into a target cell is critical. The present study is aimed at evaluating the potential of copolymers based on linear polyglycidol to act as carriers of nucleic acids. Functional copolymers with linear polyglycidol as a non-ionic hydrophilic block and a second block bearing amine hydrochloride pendant groups were prepared using previously synthesized poly(allyl glycidyl ether)-b-polyglycidol block copolymers as precursors.

StrokeWatch: An Instrument for Objective Standardized Real-Time Measurement of Door-to-Needle Times in Acute Ischemic Stroke Treatment.

Objectives: Monitoring critical time intervals in acute ischemic stroke treatment delivers metrics for quality of performance - the door-to-needle time being well-established. To resolve the conflict of self-reporting bias a "StrokeWatch" was designed - an instrument for objective standardized real-time measurement of procedural times.

Materials And Methods: An observational, monocentric analysis of patients receiving intravenous thrombolysis for acute ischemic stroke between January 2018 and September 2019 was performed based on an ongoing investigator-initiated, prospective, and blinded endpoint registry.

Cationic (Co)polymers Based on N-Substituted Polyacrylamides as Carriers of Bio-macromolecules: Polyplexes, Micelleplexes, and Spherical Nucleic Acidlike Structures.

Novel N-substituted polyacrylamides bearing a cycle with two tertiary amines, poly(4-methyl-piperazin-1-yl)-propenone (PMPP) and its block copolymers with polylactide (PMPP--PLA), are synthesized and characterized. The homopolymers are water-soluble, whereas the block copolymers self-assemble in aqueous solution into a small size ( around 30 nm), are narrowly distributed, and exhibit core-shell micelles with good colloidal stability. Both the homopolymers and copolymer micelles are positively charged (ζ-potentials in the 13.

Brain Trauma Mortality Rate Score Scale (BTMRSS): Postmortem Evaluation of the Events.

Objective: Brain trauma and its burden is becoming a significant cause of permanent damage and deterioration. Prioritization at the place of the incident and calculation of mortality are leading factors for the final management, but all of them are obtained from living patients. When the autopsies are made there is no actual score system to guide the forensic scientists in their conclusions.

Kinetic factors may reshape the dependence of crystal nucleation rate on temperature in protein bulk solution.

Here we provide an analysis of primary results obtained from a study of apoferritin crystal nucleation in compositionally invariant bulk solution at constant supersaturation ratio of the protein. The temperature dependence of the stationary crystal nucleation rate in the protein bulk solution is obtained with the help of experimentally determined probability for detection of at least one crystal per solution volume until a given time. The stationary crystal nucleation rate demonstrates unusual behavior with temperature.

Structure-Activity Relationships for the Anaesthetic and Analgaesic Properties of Aromatic Ring-Substituted Ketamine Esters.

A series of benzene ring substituted ketamine -alkyl esters were prepared from the corresponding substituted norketamines. Few of the latter have been reported since they have not been generally accessible via known routes. We report a new general route to many of these norketamines via the Neber (oxime to α-aminoketone) rearrangement of readily available substituted 2-phenycyclohexanones.

Traumatic Brain Injury and the Importance of Neurosurgical Care: 10-year Retrospective Study on Cadavers.

Objective: Traumatic brain injury (TBI) due to transport accidents is a serious cause of death and disability. In every case, however, quick response and a proper health care are required.

Materials And Methods: We collected 10-year data retrospectively from the laboratory of forensic science and toxicology in Montana, Bulgaria with the intention to show the importance of neurosurgical care in the traumatology and its connection to mortality rate.

KEA-1010, a ketamine ester analogue, retains analgesic and sedative potency but is devoid of Psychomimetic effects.

Background: Ketamine, a widely used anaesthetic and analgesic agent, is known to improve the analgesic efficacy of opioids and to attenuate central sensitisation and opioid-induced hyperalgesia. Clinical use is, however, curtailed by unwanted psychomimetic effects thought to be mediated by N-methyl-D-aspartate (NMDA) receptor antagonism. KEA-1010, a ketamine ester-analogue designed for rapid offset of hypnosis through hydrolysis mediated break-down, has been shown to result in short duration sedation yet prolonged attenuation of nociceptive responses in animal models.

Does Nationality Matter for the Gunshot Brain Injury? Ten-Year Retrospective Observational Cadaveric Comparative Study for Gunshot TBI between Greece and Bulgaria.

Objective: Penetrating brain trauma (PBT) caused by gunshot is one of the most lethal traumatic brain injuries (TBIs) and its management and confrontation is of great importance.

Methods: The authors searched retrospectively the archives from 2 similar autonomous laboratories of forensic science and toxicology in the Balkan peninsula for a 10-year period of time and included only fatal penetrating brain injuries.

Results: The study is conducted in 61 cadavers with gunshot PBT.

Multifunctional Polymer Nanocarrier for Efficient Targeted Cellular and Subcellular Anticancer Drug Delivery.

A multifunctional triblock copolymer intended for targeted drug delivery applications has been designed and successfully synthesized. Following various controlled polymerization and modification steps, a saccharide end-functionalized polyoxyethylene block was attached through an aromatic imine bond, cleavable in slightly acidic conditions, to an amphiphilic diblock copolymer comprising a biodegradable hydrophobic block and a partially modified with mitochondria targeting ligands polycationic block. The micelles formed from the triblock copolymer in aqueous media possess key functions (cleavable "stealth" shield, targeting groups) needed for safe extracellular transport, successful cell internalization, and drug delivery to the target cellular organelles.

Ketamine esters and amides as short-acting anaesthetics: Structure-activity relationships for the side-chain.

N-Aliphatic ester analogues of the non-opioid ketamine (1) retain effective anaesthetic/analgesic properties while minimising ketamine's psychomimetic side-effects. We show that the anaesthetic/analgesic properties of these ester analogues depend critically on the length (from 2 to 4 carbons), polarity and steric cross-section of the aliphatic linker chain. More stable amide and ethylsulfone analogues generally showed weaker anaesthetic/analgesic activity.

Self-Assembly of a Thermally Responsive Double-Hydrophilic Copolymer in Ethanol-Water Mixtures: The Effect of Preferential Adsorption and Co-Nonsolvency.

Lower alcohols can induce a combined collapse-swelling de-mixing transition (lower critical solution temperature (LCST)-type co-nonsolvency) in aqueous solutions of poly( N-isopropylacrylamide) (PNIPAM) by interacting with the polymer's amide groups. This interaction results in an increase of the total surface area of hydrophobic sites and destabilizes the chains. Here, we make use of this phenomenon to drive the counterintuitive self-assembly of a PNIPAM-containing double-hydrophilic graft copolymer in water-ethanol mixtures at T ≪ LCST.

Insulin/poly(ethylene glycol)-block-poly(L-lysine) Complexes: Physicochemical Properties and Protein Encapsulation.

Insulin (INS) was encapsulated into complexes with poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLys), which is a polypeptide-based block copolymer (a neutral-cationic block polyelectrolyte). The particular cationic-neutral block copolymer can complex INS molecules in aqueous media via electrostatic interactions. Light-scattering techniques are used to study the complexation process and structure of the hybrid nanoparticles in a series of buffers, as a function of protein concentration.