-
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 Nanobiotechnology Jul 2023Enterocyte uptake with high binding efficiency and minor endogenous interference remains a challenge in oral nanocarrier delivery. Enterocyte membrane-biomimetic lipids...
Enterocyte uptake with high binding efficiency and minor endogenous interference remains a challenge in oral nanocarrier delivery. Enterocyte membrane-biomimetic lipids may universally cooperate with endogenous phosphatidyl choline via a biorthogonal group. In this study, we developed a sophorolipid-associated membrane-biomimetic choline phosphate-poly(lactic-co-glycolic) acid hybrid nanoparticle (SDPN). Aided by physical stability in the gastrointestinal tract and rapid mucus diffusion provided by association with sophorolipid, these nanoparticles show improved endocytosis, driven by dipalmitoyl choline phosphate-phosphatidyl choline interaction as well as its optimized membrane fluidity and rigidity. Luteolin- and silibinin-co-loaded with SDPN alleviated breast cancer metastasis in 4T1 tumor-bearing mice by regulating the conversion of tumor-associated M2 macrophages into the M1 phenotype and reducing the proportion of the M2-phenotype through co-action on STAT3 and HIF-1α. In addition, SDPN reduces angiogenesis and regulates the matrix barrier in the tumor microenvironment. In conclusion, this membrane-biomimetic strategy is promising for improving the enterocyte uptake of oral SDPN and shows potential to alleviate breast cancer metastasis.
Topics: Mice; Animals; Tumor-Associated Macrophages; Biomimetics; Phosphorylcholine; Neoplasms; Nanoparticles; Cell Line, Tumor; Tumor Microenvironment
PubMed: 37403048
DOI: 10.1186/s12951-023-01949-5 -
Cell Biochemistry and Biophysics Dec 2022The acute phase C-reactive protein (CRP) is mainly synthesized and secreted by the liver in a cytokine-mediated response to infection or inflammation and circulates as a... (Review)
Review
The acute phase C-reactive protein (CRP) is mainly synthesized and secreted by the liver in a cytokine-mediated response to infection or inflammation and circulates as a pentamer (pCRP) in plasma. Recent studies indicate that CRP is not only a marker but is directly involved in inflammation. CRP has a vital role in host defense and inflammation, metabolic function and scavenging through its ability for calcium depended binding to exogenous and endogenous molecules having phosphocholine followed by activation of the classical complement pathway. Accumulating evidence indicates that pCRP dissociates into monomeric CRP (mCRP) and most proinflammatory actions of CRP are only expressed following dissociation of its native pentameric assembly into mCRP. The dissociation of CRP into mCRP altogether promotes the ligand-binding capability. mCRP emerges to be the main conformation of CRP that participates in the regulation of local inflammation, however, little is identified concerning what triggers the significantly enhanced actions of mCRP and their binding to diverse ligands. The separation of mCRP from pCRP may be a direct relationship between CRP and inflammation. Here we review the current literature on CRP dissociation and its interaction with different ligands. The possibility to avoid the generation of the proinflammatory potential of mCRP has driven therapeutic approaches by targeting the dissociation mechanism of pCRP or inhibition of mCRP itself during inflammation.
Topics: Humans; C-Reactive Protein; Calcium; Cytokines; Inflammation; Ligands; Phosphorylcholine; Protein Conformation
PubMed: 35997934
DOI: 10.1007/s12013-022-01089-x -
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 -
Frontiers in Immunology 2022Keloids are a fibroproliferative disease characterized by unsatisfactory therapeutic effects and a high recurrence rate.
BACKGROUND
Keloids are a fibroproliferative disease characterized by unsatisfactory therapeutic effects and a high recurrence rate.
OBJECTIVE
This study aimed to investigate keloid-related circulating metabolic signatures.
METHODS
Untargeted metabolomic analysis was performed to compare the metabolic features of 15 keloid patients with those of paired healthy volunteers in the discovery cohort. The circulating metabolic signatures were selected using the least absolute shrinkage. Furthermore, the selection operators were quantified using multiple reaction monitoring-based target metabolite detection methods in the training and test cohorts.
RESULTS
More than ten thousand metabolic features were consistently observed in all the plasma samples from the discovery cohort, and 30 significantly different metabolites were identified. Four differentially expressed metabolites including palmitoylcarnitine, sphingosine, phosphocholine, and phenylalanylisoleucine, were discovered to be related to keloid risk in the training and test cohorts. In addition, using linear and logistic regression models, the respective risk scores for keloids based on a 4-metabolite fingerprint classifier were established to distinguish keloids from healthy volunteers.
CONCLUSIONS
In summary, our findings show that the characteristics of circulating metabolic fingerprinting manifest phenotypic variation in keloid onset.
Topics: Humans; Keloid; Logistic Models; Palmitoylcarnitine; Phosphorylcholine; Sphingosine
PubMed: 36248839
DOI: 10.3389/fimmu.2022.1005366 -
Applied Spectroscopy Oct 2022Multicomponent lipid bilayers are used as models for searching the origin of spatial heterogeneities in biomembranes called lipid rafts, implying the coexistence of...
Multicomponent lipid bilayers are used as models for searching the origin of spatial heterogeneities in biomembranes called lipid rafts, implying the coexistence of domains of different phases and compositions within the lipid bilayer. The spatial organization of multicomponent lipid bilayers on a scale of a hundred nanometers remains unknown. Brillouin spectroscopy providing information about the acoustic phonons with the wavelength of several hundred nanometers has an unexplored potential for this problem. Here, we applied Brillouin spectroscopy for three binary bilayers composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-palmitoyl-sn-glycero-3-phosphocholine (DPPC), and cholesterol. The Brillouin experiment for the oriented planar multibilayers was realized for two scattering geometries involving phonons for the lateral and normal directions of the propagation. The DPPC-DOPC mixtures known for the coexistence of the solid-ordered and liquid-disordered phases had bimodal Brillouin peaks, revealing the phase domains with sizes more than a hundred nanometers. Analysis of the Brillouin data for the binary mixtures concluded that the lateral phonons are preferable for testing the lateral homogeneity of the bilayers, while the phonons spreading across the bilayers are sensitive to the layered packing at the mesoscopic scale.
Topics: Cholesterol; Lipid Bilayers; Phosphatidylcholines; Phospholipids; Phosphorylcholine; Spectrum Analysis
PubMed: 35712869
DOI: 10.1177/00037028221111147 -
The Journal of Antimicrobial... Jul 2023Cutaneous leishmaniasis (CL) is a neglected tropical disease causing a range of skin lesions for which safe and efficacious drugs are lacking. Oleylphosphocholine (OLPC)...
OBJECTIVES
Cutaneous leishmaniasis (CL) is a neglected tropical disease causing a range of skin lesions for which safe and efficacious drugs are lacking. Oleylphosphocholine (OLPC) is structurally similar to miltefosine and has previously demonstrated potent activity against visceral leishmaniasis. We here present the in vitro and in vivo efficacy of OLPC against CL-causing Leishmania species.
METHODS
The antileishmanial activities of OLPC were evaluated and compared with miltefosine in vitro against intracellular amastigotes of seven CL-causing species. Following the confirmation of significant in vitro activity, the performance of the maximum tolerated dose of OLPC was evaluated in an experimental murine model of CL followed by a dose-response titration and the efficacy evaluation of four OLPC formulations (two with a fast-release and two with a slow-release profile) using bioluminescent Leishmania major parasites.
RESULTS
OLPC demonstrated potent in vitro activity of the same order as miltefosine in the intracellular macrophage model against a range of CL-causing species. A dose of 35 mg of OLPC/kg/day administered orally for 10 days was well-tolerated and able to reduce the parasite load in the skin of L. major-infected mice to a similar extent as the positive control paromomycin (50 mg/kg/day, intraperitoneally) in both in vivo studies. Reducing the dose of OLPC resulted in inactivity and modifying the release profile using mesoporous silica nanoparticles led to a decrease in activity when solvent-based loading was used in contrast to extrusion-based loading, which had no impact on its antileishmanial efficacy.
CONCLUSIONS
Together, these data suggest that OLPC could be a promising alternative to miltefosine treatment for CL. Further investigations exploring experimental models with additional Leishmania species and skin pharmacokinetic and dynamic analyses are required.
Topics: Mice; Animals; Leishmaniasis, Cutaneous; Antiprotozoal Agents; Phosphorylcholine; Leishmaniasis, Visceral; Leishmania major; Mice, Inbred BALB C
PubMed: 37229566
DOI: 10.1093/jac/dkad162 -
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 -
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