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Anais Brasileiros de Dermatologia 2022
Topics: Antiprotozoal Agents; Cardiotoxicity; Humans; Leishmaniasis, Visceral; Phosphorylcholine
PubMed: 35654652
DOI: 10.1016/j.abd.2022.03.002 -
Journal of Biomaterials Science.... 2018We summarize the development and evaluation of new type of phospholipid polymers as a solubilizer for poorly water-soluble compounds. That is, a water-soluble and... (Review)
Review
We summarize the development and evaluation of new type of phospholipid polymers as a solubilizer for poorly water-soluble compounds. That is, a water-soluble and amphiphilic poly(2-methacryloyloxyethyl phosphorylcholine-random-n-butyl methacrylate) contains 30 mol% hydrophilic 2-methacryloyloxyethyl phosphorylcholine units and its weight-averaged molecular weight is around 5.0 × 10. When the polymer is dissolved in an aqueous medium, a large portion of hydrophobic n-butyl methacrylate units assemble, forming polymer aggregates. To avoid severe biological reactions caused by conventional solubilizers, the phospholipid polymer can be applied for the solubilization of poorly water-soluble bioactive compounds. The polarity inside these polymer aggregate is the same as that of ethanol and n-butanol. Therefore, bioactive compounds, whose solubility is poor in water but good in these alcohols, can be entrapped in the polymer aggregate. The phospholipid polymer can penetrate the cell membrane by molecular diffusion, carrying inside the cell the bioactive compound, without exhibiting significant cytotoxicity. Several animal experiments have revealed that the pharmacological performance of various bioactive compound/phospholipid polymer complexes is excellent. Furthermore, functionalization of the polymer aggregate with biomolecules, such as antibodies and oligonucleotides, can be done, leading to selective capturing of the target molecules. These examples clearly indicate that water-soluble and amphiphilic phospholipid polymer is a candidate for preparing safer formulations and more effective pharmaceutical treatment with several bioactive compounds.
Topics: Animals; Drug Carriers; Hydrophobic and Hydrophilic Interactions; Methacrylates; Phospholipids; Phosphorylcholine; Solubility; Water
PubMed: 28891422
DOI: 10.1080/09205063.2017.1377023 -
Journal of Materials Chemistry. B Apr 2022Bioinspired materials have attracted attention in a wide range of fields. Among these materials, a polymer family containing 2-methacryloyloxyethyl phosphorylcholine... (Review)
Review
Bioinspired materials have attracted attention in a wide range of fields. Among these materials, a polymer family containing 2-methacryloyloxyethyl phosphorylcholine (MPC), which has a zwitterionic phosphorylcholine headgroup inspired by the structure of the cell membrane, has shown an outstanding ability to prevent nonspecific protein adsorption. This property makes MPC polymers excellent materials for the construction of biocompatible surfaces and interfaces with high antibiofouling performance for both macroscopic and microscopic applications. In this review, we summarize recent progress in the design, synthesis, and application of MPC polymers for biodevices with characteristic length scales ranging from millimeters to nanometers, with a focus on their applications in microfluidic devices, biosensors/bioprobes, artificial implants, and drug delivery systems. Finally, future perspectives and challenges in this field are discussed.
Topics: Biocompatible Materials; Methacrylates; Phosphorylcholine; Polymers
PubMed: 35142776
DOI: 10.1039/d1tb02675e -
Journal of Materials Chemistry. B Jun 2023This work developed innovative poly(ester-urethane) materials double-modified by quercetin (QC) and phosphorylcholine (PC) with improved antibacterial activity and...
Enhanced hemocompatibility and antibacterial activity of biodegradable poly(ester-urethane) modified with quercetin and phosphorylcholine for durable blood-contacting applications.
This work developed innovative poly(ester-urethane) materials double-modified by quercetin (QC) and phosphorylcholine (PC) with improved antibacterial activity and hemocompatibility. The functional monomer of PC-diol was first synthesized a click reaction between 2-methacryloyloxyethyl phosphorylcholine and α-thioglycerol; the NCO-terminated prepolymer was subsequently prepared by a one-pot condensation method of PC-diol, poly(ε-caprolactone) diol, and excess isophorone diisocyanate; finally, the prepolymer was chain-extended with QC to produce the linear products (PEU-PQs). H NMR, FT-IR, and XPS techniques confirmed the successful introduction of PC and QC, and the in-depth characterization of the cast PEU-PQ films was carried out. Although a low crystallinity was demonstrated by XRD and thermal analysis, the films exhibited excellent tensile stress and stretchability due to the interchain multiple hydrogen bonds. The introduction of PC groups enhanced the surface hydrophilicity, water absorption, and the hydrolytic degradation rate of the film materials. Inhibition zone tests presented that the QC-based PEU-PQs had effective antibacterial activity against and . The biological evaluations of the materials were performed by protein absorption, platelet adhesion, and cytotoxic test and by subcutaneous implantation, which demonstrated superior surface hemocompatibility and biocompatibility. Collectively, the PEU-PQ biomaterials hold a prospective application in durable blood-contacting devices.
Topics: Polyurethanes; Quercetin; Spectroscopy, Fourier Transform Infrared; Phosphorylcholine; Esters; Escherichia coli; Staphylococcus aureus
PubMed: 37291983
DOI: 10.1039/d3tb00596h -
Langmuir : the ACS Journal of Surfaces... Nov 2023Surface modification using zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers is commonly performed to fabricate interfaces that reduce nonspecific... (Review)
Review
Surface modification using zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers is commonly performed to fabricate interfaces that reduce nonspecific fouling by biomolecules and cells. Accordingly, several clinically used devices, such as guide wires, stents, oxygenators, left ventricular assist devices, and microcatheters have been modified using MPC polymers. The specific types of surface modifications vary across substrates and applications. Recently, photoreactions have garnered attention for surface modification due to their stability and tunability. This review highlights various studies that employed photoreactions to modify surfaces using MPC polymers, especially photoinduced graft polymerization of MPC. In addition to antifouling materials, several micromanipulated, long-lasting hydrophilic, and super antiwear surfaces are summarized. Furthermore, several photoreactive MPC polymers that can be used to control interactions between biomolecules and materials are presented along with their potential to form selective recognition surfaces that target biomolecules for biosensors and diagnostic devices.
Topics: Biocompatible Materials; Phosphorylcholine; Polymers; Methacrylates; Hydrophobic and Hydrophilic Interactions; Surface Properties
PubMed: 37899752
DOI: 10.1021/acs.langmuir.3c02696 -
Journal of Liposome Research Sep 2017Conventional chemotherapy for leishmaniasis includes considerably toxic drugs and reports of drug-resistance are not uncommon. Liposomal encapsulated drugs appear as an... (Review)
Review
Conventional chemotherapy for leishmaniasis includes considerably toxic drugs and reports of drug-resistance are not uncommon. Liposomal encapsulated drugs appear as an option for the treatment of leishmaniasis, providing greater efficacy for the active and reducing its side effects by promoting superior tissue absorption, favouring drug penetration into the macrophages, and retarding its clearance from the site of action. In this paper, a review on the advances achieved with liposome-based anti-leishmaniasis drug delivery systems is presented. Formulations prepared with either conventional or modified (sugar-coated, cationic, niosomes, peptides- and antibodies-bounded) liposomes for the delivery of pentavalent antimonials, amphotericin B, pentamidine, paromomycyn, and miltefosine were covered. This literature review depicts a scenario of no effective therapeutic agents for the treatment of this neglected disease, where liposomal formulations appear to improve the effectiveness of the available antileishmania agents.
Topics: Amphotericin B; Animals; Antiprotozoal Agents; Drug Compounding; Drug Delivery Systems; Drug Liberation; Humans; Leishmaniasis; Liposomes; Nanoparticles; Paromomycin; Particle Size; Pentamidine; Phosphorylcholine; Surface Properties
PubMed: 28874072
DOI: 10.1080/08982104.2017.1376682 -
Immunologic Research Dec 2018The distinction that in areas where helminthic infections are common, autoimmune diseases are less prevalent, led to the investigation of immune modulatory properties of... (Review)
Review
The distinction that in areas where helminthic infections are common, autoimmune diseases are less prevalent, led to the investigation of immune modulatory properties of helminths and their derivatives. Such are phosphorylcholine (PC) moieties which are a component of secreted products of helminths. PC has been broadly studied for its attenuating effects on the human immune system. In an attempt to develop a novel therapeutic small molecule for the treatment of autoimmune conditions, we have conjugated PC with tuftsin, a natural immunomodulatory tetrapeptide, to create TPC. Herein, we review our findings regarding the effects of TPC in murine models of three autoimmune diseases-systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and rheumatic arthritis (RA), as well as ex-vivo samples from giant cell arteritis (GCA) patients. In all four disease models examined, TPC was shown to attenuate the inflammatory response by reducing expression of pro-inflammatory cytokines and altering the phenotype of T cell expression. In murine models, TPC has further produced a significant improvement in clinical disease scores with no significant side effects noted. Our findings suggest TPC presents promising potential as a novel therapeutic agent for the effective treatment of various autoimmune conditions.
Topics: Animals; Autoimmune Diseases; Autoimmunity; Helminthiasis; Helminths; Humans; Inflammation; Phosphorylcholine; Tuftsin
PubMed: 30554380
DOI: 10.1007/s12026-018-9051-2 -
The Lancet. Infectious Diseases Jan 2024For the past 15 years, trials of combination therapy options for visceral leishmaniasis have been conducted with the aim of identifying effective, and safe treatment... (Review)
Review
For the past 15 years, trials of combination therapy options for visceral leishmaniasis have been conducted with the aim of identifying effective, and safe treatment regimens that were shorter than existing monotherapy regimens and could also prevent or delay the emergence of drug resistance. Although first-line treatment currently relies on combination therapy in east Africa, this is not true in Latin America owing to disappointing trial results, with lower than expected efficacy seen for the combination treatment group. By contrast, several effective combination therapy regimens have been identified through trials on the Indian subcontinent; yet, first-line therapy is still AmBisome monotherapy as the drug is part of a free donation programme and is highly effective in this region. Achieving a short all-oral combination treatment will require new chemical entities, several of which are currently under evaluation. Future studies should systematically include pharmacological substudies to ensure optimal dosing for all patient groups. To achieve maximal impact of new combination treatments, mechanisms to ensure drug availability and access after trials should be established. Enhancing the longevity of current and novel treatments will require effective systems for early detection of emerging drug resistance.
Topics: Humans; Leishmaniasis, Visceral; Antiprotozoal Agents; Drug Therapy, Combination; Phosphorylcholine; Combined Modality Therapy
PubMed: 37640031
DOI: 10.1016/S1473-3099(23)00353-5 -
PLoS Neglected Tropical Diseases May 2021Cutaneous leishmaniasis (CL) in Ethiopia, caused by Leishmania aethiopica, is often severe and hard to treat compared to CL caused by other species elsewhere....
BACKGROUND
Cutaneous leishmaniasis (CL) in Ethiopia, caused by Leishmania aethiopica, is often severe and hard to treat compared to CL caused by other species elsewhere. Miltefosine is the only oral anti-leishmanial drug, with a favorable side-effect profile compared to routinely available sodium stibogluconate (SSG), but evidence about its use for L. aethiopica is lacking.
METHODOLOGY AND PRINCIPAL FINDINGS
In an observational cohort study, treatment outcomes, safety and adherence among CL patients who required systemic treatment and received miltefosine for 28 days in Boru Meda Hospital and University of Gondar Hospital were studied. Patient cure was defined as 100% flattening for non-ulcerated lesions and 100% flattening and 100% re-epithelization for ulcerated lesions. Outcomes were documented for day 28, 90 and 180, both per site, and pooled, adjusting for site as a fixed effect with effect coding. Among 94 included patients (32 in Gondar, 62 in Boru Meda), median lesion duration was 12 months, median size six cm, and mucosal involvement (46.8%) and diffuse (30.9%) lesions were common. Adherence to miltefosine was good, and side-effects were tolerable. Initial outcomes at day 28 were promising, with 68.8% and 94.0% of patients having good improvement or cure in Gondar and Boru Meda respectively. In Boru Meda, outcomes were good with 72.7% and 72.9% cure at day 90 and day 180 respectively. In Gondar, results were less promising, with only 12.5% and 26.7% cure at day 90 and day 180, although confidence intervals were wide. In pooled estimates, 48.7% of patients reached cure at day 180, and 32.3% relapsed. Outcomes were better in Boru Meda Hospital, for smaller lesions and for mucosal lesions.
CONCLUSIONS/SIGNIFICANCE
Based on miltefosine's good initial response, tolerable side-effects, tablet-form, we propose to include miltefosine for future clinical trials using extended treatment schedules, combination therapy, or targeting specific subgroups.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04004754.
Topics: Administration, Oral; Adolescent; Adult; Antiprotozoal Agents; Cohort Studies; Ethiopia; Female; Humans; Leishmania; Leishmaniasis, Cutaneous; Male; Phosphorylcholine; Pilot Projects; Treatment Adherence and Compliance; Treatment Outcome
PubMed: 34048461
DOI: 10.1371/journal.pntd.0009460 -
Spectrochimica Acta. Part A, Molecular... Apr 2017The Raman, MIR and UV-vis spectroscopy have been used to characterize Omafilcon A material constructing the one of the Proclear family contact lenses. The Omafilcon A is...
The Raman, MIR and UV-vis spectroscopy have been used to characterize Omafilcon A material constructing the one of the Proclear family contact lenses. The Omafilcon A is hydrogel material composed of 2-hydroxyethyl methacrylate (HEMA) and 2-methacryloyloxyethyl phosphorylcholine (PC) polymers crosslinked with ethyleneglycol dimethacrylate (EGDMA). Vibrational and electronic properties of the Omafilcon A material were also investigated by quantum chemical calculations. Experimentally obtained Raman, MIR and optical spectra were compared to the theoretical ones calculated applying RHF and DFT methodology. The quantum chemical calculations were performed for isolated monomers of lenses compounds as well as for their dimers and trimers to elucidate the effect of Omafilcon A polymerization and the role of an individual components.
Topics: Contact Lenses; Models, Molecular; Molecular Conformation; Phosphorylcholine; Polymers; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Vibration
PubMed: 28081493
DOI: 10.1016/j.saa.2017.01.013