The Critical Role of Aromatic-Aromatic Drug-Polymer Interactions to Provide Nanomedicines Containing Chloroquine: A Simple Proposal to Provide High Encapsulation, High Stability, and Prolonged Drug Release

Mapping Intimacies ◽

10.21203/rs.3.rs-101145/v1 ◽

2020 ◽

Author(s):

María Gabriela Villamizar-Sarmiento ◽

Ignacio Moreno-Villoslada ◽

Felipe Oyarzun-Ampuero

Keyword(s):

Chronic Diseases ◽

Drug Loading ◽

Critical Role ◽

Molar Ratio ◽

High Yield ◽

Prolonged Release ◽

Aromatic Group ◽

Aromatic Interactions ◽

Very High

Abstract Background: Chloroquine (CQ) is a drug commonly used to treat malaria. CQ has also gained interest for the treatment of other chronic diseases such as arthritis, lupus, cancer, diabetes, atherosclerosis, and dermatomyositis, among others. Since CQ is hydrophilic and low molecular-weight, attractive interactions with polymers in aqueous medium are weaker than with water, so that low encapsulation together with uncontrolled and fast release is observed. Importantly, a long-term administration of CQ is suggested, thus the development of formulations with controlled and prolonged release is desirable. Results: Here we propose the use of aromatic interactions between the cationic CQ and the FDA approved polymer poly(sodium 4-styrenesulfonate) (PSS) for the formation and stabilization of nanoparticles (NPs). The strategy consists on the simple mixture of two aqueous solutions containing the oppositelly charged molecules. UV-vis and NMR spectroscopy evidence intimate aromatic-aromatic interactions between CQ and PSS. CQ/PSS molar ratios from 0.2 to 0.5 allow obtaining NPs with spherical shape, size in the range of 170-410 nm, zeta potential from -18 to -45 mV, and particles number in the range of 0.9 - 6.6 x 1010 NPs/mL. Selected NPs (CQ/PSS molar ratio 0.4) are stable to wide variations in ionic strength (0-200 mM), pH (2-10) and temperature (20-50 °C). In addition, CQ/polymer 0.4 was also tested but with the absence of the aromatic group in the polymer, and providing smaller (70 nm), lower-concentrated (6.1 x 109 NPs/mL), and unstable particles, confirming the key role of the aromatic group. Furthermore, CQ/PSS NPs are stable during months and can be converted to a reconstitutable powder. Importantly, the selected NPs (CQ/PSS 0.4) show full drug association efficiency (100 %), very high drug loading (49 %), very high yield (89 %), and evidencing a drug entrapment/release governed by kinetic associations (≈99 %). Finally, release studies evidence a controlled and prolonged delivery. Conclusions: Considering the potential uses of CQ for chronic diseases, and the simplicity and efficiency of our proposal, it could be considered as a valuable alternative to developed nanomedicines. In addition, this strategy could be used for other drugs and polymers showing similar characteristics to CQ and PSS.

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Critical Role of Virion-Associated Cholesterol and Sphingolipid in Hepatitis C Virus Infection

Journal of Virology ◽

10.1128/jvi.02530-07 ◽

2008 ◽

Vol 82 (12) ◽

pp. 5715-5724 ◽

Cited By ~ 139

Author(s):

Hideki Aizaki ◽

Kenichi Morikawa ◽

Masayoshi Fukasawa ◽

Hiromichi Hara ◽

Yasushi Inoue ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Cell Attachment ◽

Critical Role ◽

Molar Ratio ◽

Complete Life Cycle ◽

Rna Accumulation ◽

Hydrolysis Of ◽

Hcv Structural Proteins

ABSTRACT In this study, we establish that cholesterol and sphingolipid associated with hepatitis C virus (HCV) particles are important for virion maturation and infectivity. In a recently developed culture system enabling study of the complete life cycle of HCV, mature virions were enriched with cholesterol as assessed by the molar ratio of cholesterol to phospholipid in virion and cell membranes. Depletion of cholesterol from the virus or hydrolysis of virion-associated sphingomyelin almost completely abolished HCV infectivity. Supplementation of cholesterol-depleted virus with exogenous cholesterol enhanced infectivity to a level equivalent to that of the untreated control. Cholesterol-depleted or sphingomyelin-hydrolyzed virus had markedly defective internalization, but no influence on cell attachment was observed. Significant portions of HCV structural proteins partitioned into cellular detergent-resistant, lipid-raft-like membranes. Combined with the observation that inhibitors of the sphingolipid biosynthetic pathway block virion production, but not RNA accumulation, in a JFH-1 isolate, our findings suggest that alteration of the lipid composition of HCV particles might be a useful approach in the design of anti-HCV therapy.

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Matrix Metalloproteinase-3 in Myasthenia Gravis Compared to Other Neurological Disorders and Healthy Controls

Autoimmune Diseases ◽

10.4061/2011/151258 ◽

2011 ◽

Vol 2011 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Steven P. Luckman ◽

Nils Erik Gilhus ◽

Fredrik Romi

Keyword(s):

Myasthenia Gravis ◽

Neurological Disorders ◽

Critical Role ◽

Control Group ◽

Healthy Controls ◽

Stroke Patients ◽

Pathogenic Role ◽

Matrix Metalloproteinase 3 ◽

Very High

MMP-3 is capable of degrading a variety of proteins, including agrin, which plays a critical role in neuromuscular signaling by controlling acetylcholine receptor clustering. High MMP-3 levels in a proportion of myasthenia gravis (MG) patients have been reported. A pathogenic role of MMP-3 in other neurological disorders has been suggested but not proven. We have therefore examined the levels of MMP-3 in 124 MG patients and compared them to 59 multiple sclerosis (MS) patients, 74 epilepsy patients, 33 acute stroke patients, and 90 healthy controls. 15.3% of the patients in the MG group were MMP-3-positive (defined as higher than cutoff value 48 ng/mL) with very high mean MMP-3 concentration (79.9 ng/mL), whereas the proportion of MMP-3 positive patients in the MS (3.4%), epilepsy (6.7%), stroke (0%), and the control group (4.4%) was significantly lower. Mean MMP-3 concentration in the total MG group (25.5 ng/mL) was significantly higher than in the MS (16.6 ng/mL) and stroke (11.7 ng/mL) groups, but did not differ significantly from the epilepsy (19.4 ng/mL) and the control group (23.4 ng/mL). MMP-3 may have a specific pathogenic effect in MG in addition to being associated with autoimmune diseases in general.

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Influence of Heterogeneous Catalysts and Reaction Parameters on the Acetylation of Glycerol to Acetin: A Review

Applied Sciences ◽

10.3390/app10207155 ◽

2020 ◽

Vol 10 (20) ◽

pp. 7155

Author(s):

Usman Idris Nda-Umar ◽

Irmawati Binti Ramli ◽

Ernee Noryana Muhamad ◽

Norsahida Azri ◽

Uchenna Fidelis Amadi ◽

...

Keyword(s):

Heterogeneous Catalysts ◽

Critical Role ◽

Economic Value ◽

Biodiesel Production ◽

Molar Ratio ◽

Fuel Additive ◽

Reaction Parameters ◽

The Many ◽

Catalyst Load

Glycerol, a polyhydric alcohol, is currently receiving greater attention worldwide in view of its glut in the market occasioned by the recent upsurge in biodiesel production. The acetylation of glycerol to acetin (acetyl glycerol) is one of the many pathways of upgrading glycerol to fine chemicals. Acetin, which could be mono, di, and or triacetin, has versatile applications in the cosmetics, medicines, food, polymer, and fuel industries as a humectant, emulsifier, plasticizer, and fuel additive and so it is of high economic value. Given the critical role of catalysts in green chemistry, this paper reports the influence of the different heterogeneous catalysts used in glycerol acetylation. It also reviewed the influence of catalyst load, temperature, molar ratio, and the time on the reaction.

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Rapid and high yield production of phospholipids enriched in CLA via acidolysis: The critical role of the enzyme immobilization protocol

Food Chemistry ◽

10.1016/j.foodchem.2019.05.107 ◽

2019 ◽

Vol 296 ◽

pp. 123-131 ◽

Cited By ~ 10

Author(s):

Carlos M. Verdasco-Martín ◽

Carlos Corchado-Lopo ◽

Roberto Fernández-Lafuente ◽

Cristina Otero

Keyword(s):

Enzyme Immobilization ◽

Critical Role ◽

High Yield ◽

Yield Production ◽

High Yield Production

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Controlled Synthesis of Triangular Silver Nanoplates by Gelatin–Chitosan Mixture and the Influence of Their Shape on Antibacterial Activity

Processes ◽

10.3390/pr7120873 ◽

2019 ◽

Vol 7 (12) ◽

pp. 873 ◽

Cited By ~ 2

Author(s):

Quoc Khuong Vo ◽

Duc Duy Phung ◽

Quynh Nhu Vo Nguyen ◽

Hong Hoang Thi ◽

Nhat Hang Nguyen Thi ◽

...

Keyword(s):

Antibacterial Activity ◽

Critical Role ◽

High Yield ◽

Synthesis Process ◽

Silver Nanostructures ◽

Experimental Conditions ◽

Silver Nanoplates ◽

Triangular Silver Nanoplates ◽

Ft Ir

Triangular silver nanoplates were prepared by using the seeding growth approach with the presence of citrate-stabilized silver seeds and a mixture of gelatin–chitosan as the protecting agent. By understanding the critical role of reaction components, the synthesis process was improved to prepare the triangular nanoplates with high yield and efficiency. Different morphologies of silver nanostructures, such as triangular nanoplates, hexagonal nanoprisms, or nanodisks, can be obtained by changing experimental parameters, including precursor AgNO3 volume, gelatin–chitosan concentration ratios, and the pH conditions. The edge lengths of triangular silver nanoplates were successfully controlled, primarily through the addition of silver nitrate under appropriate condition. As-prepared triangular silver nanoplates were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-Vis, Fourier transform infrared spectroscopy (FT-IR), and X-Ray diffraction (XRD). Silver nanoplates had an average edge length of 65–80 nm depending on experimental conditions and exhibited a surface plasma resonance absorbance peak at 340, 450, and 700 nm. The specific interactions of gelatin and chitosan with triangular AgNPs were demonstrated by FT-IR. Based on the characterization, the growth mechanism of triangular silver nanoplates was theoretically proposed regarding the twinned crystal of the initial nanoparticle seeds and the crystal face-blocking role of the gelatin–chitosan mixture. Moreover, the antibacterial activity of triangular silver nanoplates was considerably improved in comparison with that of spherical shape when tested against Gram-positive and Gram-negative bacteria species, with 6.0 ug/mL of triangular silver nanoplates as the MBC (Minimum bactericidal concentration) for Escherichia coli and Vibrio cholera, and 8.0 ug/mL as the MBC for Staphylococcus aureus and Pseudomonas aeruginosa. The MIC (Minimum inhibitory concentration) of triangular Ag nanoplates was 4.0 ug/mL for E. coli, V. cholera, S. aureus, and P. aeruginosa.

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The Role of the SLP in Autism Spectrum Disorder Screening and Assessment

Perspectives on Language Learning and Education ◽

10.1044/lle15.2.50 ◽

2008 ◽

Vol 15 (2) ◽

pp. 50-59 ◽

Cited By ~ 1

Author(s):

Amy Philofsky

Keyword(s):

Language Development ◽

Critical Role ◽

Children With Autism ◽

Autism Spectrum ◽

Children With Asd ◽

Prevalence Estimates ◽

Notable Increase ◽

Screening Assessment ◽

Critical Components

AbstractRecent prevalence estimates for autism have been alarming as a function of the notable increase. Speech-language pathologists play a critical role in screening, assessment and intervention for children with autism. This article reviews signs that may be indicative of autism at different stages of language development, and discusses the importance of several psychometric properties—sensitivity and specificity—in utilizing screening measures for children with autism. Critical components of assessment for children with autism are reviewed. This article concludes with examples of intervention targets for children with ASD at various levels of language development.

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