scholarly journals Evaluation of the Antiviral Activity of Sitagliptin-Glatiramer Acetate Nano-Conjugates against SARS-CoV-2 Virus

2021 ◽  
Vol 14 (3) ◽  
pp. 178
Author(s):  
Nabil A. Alhakamy ◽  
Osama A. A. Ahmed ◽  
Tarek S. Ibrahim ◽  
Hibah M. Aldawsari ◽  
Khalid Eljaaly ◽  
...  
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Glatiramer Acetate ◽  
Molar Ratio ◽  
Target Cells ◽  
Protease Inhibition ◽  
23 Factorial Design ◽  
Ic50 Values ◽  
Approved Drugs ◽  
3Cl Protease

The outbreak of the COVID-19 pandemic in China has become an urgent health and economic challenge. There is a current race for developing strategies to treat and/or prevent COVID-19 worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of coronavirus that causes COVID-19. The aim of the present work was to evaluate the efficacy of the combined complex (nano-conjugates) of two FDA-approved drugs, sitagliptin (SIT) and glatiramer acetate (GA), against a human isolate of the SARS-CoV-2 virus. SIT-GA nano-conjugates were prepared according to a full three-factor bilevel (23) factorial design. The SIT concentration (mM, X1), GA concentration (mM, X2), and pH (X3) were selected as the factors. The particle size (nm, Y1) and zeta potential (mV, Y2) were assessed as responses. Characterization of the optimized formula for the Fourier-transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM) was carried out. In addition, the half-maximal inhibitory concentration (IC50) in Vero-E6 epithelial cells previously infected with the virus was investigated. The results revealed that the optimized formula of the prepared complex was a 1:1 SIT:GA molar ratio at a pH of 10, which met the required criteria with a desirability value of 0.878 and had a particle size and zeta potential at values of 77.42 nm and 27.67 V, respectively. The SIT-GA nano-complex showed antiviral potential against an isolate of SARS-CoV-2 with IC50 values of 16.14, 14.09, and 8.52 µM for SIT, GA, and SIT-GA nano-conjugates, respectively. Molecular docking has shown that the formula’s components have a high binding affinity to the COVID 3CL protease, essential for coronavirus replication, paralleled by 3CL protease inhibition (IC50 = 2.87 µM). An optimized formulation of SIT-GA could guarantee both enhanced deliveries to target cells and improved cellular uptake. Further clinical studies are being carried out to validate the clinical efficacy of the optimized formulation against SARS-CoV-2.

scholarly journals Repurposing of Sitagliptin- Melittin Optimized Nanoformula against SARS-CoV-2; Antiviral Screening and Molecular Docking Studies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 307
Author(s):  
Mohammed Al-Rabia ◽  
Nabil Alhakamy ◽  
Osama Ahmed ◽  
Khalid Eljaaly ◽  
Ahmed Aloafi ◽  
...  
Keyword(s):  
Particle Size ◽  
Molecular Docking ◽  
Zeta Potential ◽  
Docking Studies ◽  
Target Cells ◽  
Protease Inhibition ◽  
23 Factorial Design ◽  
Ic50 Values

The outbreak of the COVID-19 pandemic in China has become an urgent health and economic challenge. The objective of the current work was to evaluate the efficacy of the combined complex of Sitagliptin (SIT) with melittin (MEL) against SARS-CoV-2 virus. SIT-MEL nano-conjugates were optimized by a full three-factor bi-level (23) factorial design. In addition, SIT concentration (mM, X1), MEL concentration (mM, X2), and pH (X3) were selected as the critical factors. Particle size (nm, Y1) and zeta potential (mV, Y2) were assessed as responses. Characterization of the optimized formula for Fourier-transformed infrared (FTIR) was carried out. The optimized formula showed particle size and zeta potential values of 77.42 nm and 27.67 mV, respectively. When compared with SIT and MEL, the combination of SIT-MEL complex has shown anti-viral potential against isolate of SARS-CoV-2 with IC50 values of 8.439 μM with significant improvement (p < 0.001). In addition, the complex showed IC50 in vitro 3CL-protease inhibition with IC50 7.216 µM. Molecular docking has revealed that formula components have good predicted pocket accommodation of the SARS-CoV-2 3-CL protease. An optimized formulation of SIT-MEL could guarantee both enhanced delivery to the target cells and the enhanced cellular uptake with promising activities against SARS-CoV-2.

scholarly journals 503. In vitro Evaluation of Sitagliptin-HIV-1 Trans-activator Transcription Peptide Nano-formula for Antiviral Activity Against SARS-CoV-2: Drug Repurposing Approach

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S354-S354
Author(s):  
Khalid Eljaaly ◽  
Hani Asfour ◽  
Tarek Ibrahim ◽  
Osama Ahmed ◽  
Nabil Alhakamy ◽  
...  
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Drug Repurposing ◽  
Inhibitory Effect ◽  
Molar Ratio ◽  
Target Cells ◽  
Protease Inhibition ◽  
3Cl Protease ◽  
Hiv 1

Abstract Background The outbreak of COVID-19 pandemic in China regarded as a major health/economic hazard. The importance of coming up with mechanisms for preventing or treating COVID-19 has been felt across the world. This work aimed at examining the efficiency of Sitagliptin (SIT) and human immunodeficiency virus type 1 (HIV-1) trans-activator transcription peptide (TAT) against SARS-CoV-2. Methods SIT-TAT nano-conjugates were prepared according to a full three-factor bi-level (23) factorial design. SIT concentration (mM, X1), TAT concentration (mM, X2), and pH (X3) were selected as the factors. Particle size (nm, Y1) and zeta potential (mV, Y2) were assessed as responses. Characterization of the optimized formula for Fourier-transformed infrared (FTIR) and Transmission electron microscope was carried out. In addition, IC50 in Vero E6 cells, In vitro 3CL-protease inhibition and docking tests were investigated. Results The prepared complex’s formula was as follows 1: 1 SIT: TAT molar ratio, whereas zeta potential and particle size values were at 34.17 mV and 97.19 nm, respectively. This combination did exhibit its antiviral potentiality against SARS-CoV-2 via IC50 values of 9.083 5.415, and 16.14 µM for TAT, SIT-TAT, and SIT, respectively. In addition, the complex SIT-TAT showed a significant (P &lt; 0.001) viral-3CL-protease inhibitory effect (IC50 = 3.959 µM ± 0.011) in comparison to isolated components (IC50 = 10.93 µM ± 0.25) and TAT (IC50 = 8.128 µM ± 0.42). This was further confirmed via in silico study. Molecular docking investigation has shown promising binding affinity of the formula components towards SARS-CoV-2 main protease (3-CL). Conclusion While offering significant binding interactions with protein’s key pocket residues, an optimized formulation of SIT-TAT could guarantee both the enhanced delivery to the target cells and the improved cellular uptake. The presented findings would guarantee further investigations regarding formula optimization against SARS-CoV-2. Disclosures All Authors: No reported disclosures

Formulation and Evaluation of Nanosuspension of Simvastatin

2015 ◽  
Vol 8 (2) ◽  
pp. 2858-2873
Author(s):  
Rupali L. Shid ◽  
Shashikant N. Dhole ◽  
Nilesh Kulkarni ◽  
Santosh L Shid
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Factorial Design ◽  
Dissolution Rate ◽  
In Vitro Dissolution ◽  
Total Drug ◽  
23 Factorial Design ◽  
Rate Of Dissolution

Poor water solubility and slow dissolution rate are issues for the majority of upcoming and existing biologically active compounds. Simvastatin is poorly water-soluble drug and its bioavailability is very low from its crystalline form. The purpose of this study wasto increase the solubility and dissolution rate of simvastatin by the  preparation of nanosuspension by emulsification solvent diffusion method at laboratory scale. Prepared nanosus-pension was evaluated for its particle size and in vitro dissolution study and characterized by zeta potential,differential scanning calorimetry (DSC) and X-Ray diffractometry (XRD), motic digital microscopy, entrapment efficiency, total drug content, saturated solubility study and in vivo study. A 23 factorial design was employed to study the effect of independent variables, amount of SLS (X1), amount of PVPK-30 (X2) and poloxamer-188 (X3) and dependent variables are total drug content and polydispersity Index. The obtained results showed that particle size (nm) and rate of dissolution has been improved when nanosuspension prepared with the higherconcentration of PVPK-30 with the higher concentration of PVP K-30 and Poloxamer-188 and lower concentration of SLS. The particle size and zeta potential of optimized formulation was found to be 258.3 nm and 23.43. The rate of dissolution of the optimized nanosuspension was enhanced (90% in 60min), relative to plain simvastatin  (21% in 60 min), mainly due to the formation of nanosized particles. These results indicate the suitability of 23 factorial  design for preparation of simvastatin loaded nano-suspension significantly improved in vitro dissolution rate and thus possibly enhance fast onset of therapeutic drug effect. In vivo study shows increase in bioavailability in nanosuspension formulation than the plain simvastatin drug.

scholarly journals Formulation and Characterization of Carvedilol Leciplex for Glaucoma Treatment: In-Vitro, Ex-Vivo and In-Vivo Study

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 197 ◽  
Author(s):  
Doaa Hassan ◽  
Rehab Abdelmonem ◽  
Menna Abdellatif
Keyword(s):  
Particle Size ◽  
Intraocular Pressure ◽  
Zeta Potential ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Molar Ratio ◽  
Duration Of Action ◽  
Corneal Permeability ◽  
Glaucoma Treatment

This study evaluated the efficacy of cationic nanoparticle (leciplex) to deliver carvedilol to ocular surface for glaucoma treatment as recent studies pointed out the effect of topical carvedilol on intraocular pressure, therefore carvedilol loaded leciplex formulae were prepared using soy phosphatidyl choline (SPC) and cationic surfactant (CTAB/DDAB) and characterized for morphology, entrapment efficiency, particle size, zeta potential and ex-vivo corneal permeation. Then the selected formula was evaluated via in-vivo studies in comparison with carvedilol solution. Leciplex nanoparticles appeared spherical in shape with entrapment efficiency exceeded 95% in all formulae. Leciplex formula composed of SPC and DDAB in (1:1) molar ratio showed the smallest particle size (16.04 ± 1.2 nm), highest zeta potential value (53.9 ± 0.91 mv) and highest apparent corneal permeability coefficient (0.1157 cm/h). Carvedilol leciplex reduced intraocular pressure (IOP) to normal range in ocular hypertensive rabbits after 30 min and duration of action lasted for 24 h, while carvedilol solution reduced IOP to normal value after 60 min and duration of action lasted for 6 h. Furthermore, histological examination of eyeballs of rabbits treated with carvedilol leciplex showed improvement of retinal atrophy of glaucomatous eyes. This study concluded that leciplex improve transcorneal permeation and bioavailability of carvedilol.

scholarly journals Assessment of the Effect of PLGA Co-polymers and PEG on the Formation and Characteristics of PLGA-PEG-PLGA Co-block Polymer Using Statistical Approach

2019 ◽  
Vol 9 (3) ◽  
pp. 382-392 ◽  
Author(s):  
Teuku Nanda Saifullah Sulaiman ◽  
Dwi Larasati ◽  
Akhmad Kharis Nugroho ◽  
Syaiful Choiri
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Statistical Approach ◽  
Phase Particle ◽  
Entrapment Efficiency ◽  
Molar Ratio ◽  
Scanning Calorimetry ◽  
Particle Size Reduction ◽  
Block Polymers ◽  
Block Polymer

Purpose: To assess the effect of the lactic acid (LA)-to-glycolic acid (GA) molar ratio and polyethylene glycol (PEG) concentration on the formation of poly-lactide co-glycolide acid (PLGA)-PEG-PLGA co-block polymers simultaneously using statistical approach. Methods: A 22 full factorial design with the addition of a point in the center of the design, namely curvature, was applied. Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR) were performed to confirm the formation of the co-block polymer. Simvastatin (SMV), a drug model was incorporated into the nano-polymeric micellar (NpM) of PLGA-PEG-PLGA followed by solubility phase, particle size, zeta potential, and entrapment efficiency characterizations. Results: FTIR, DSC, and NMR successfully confirmed the formation of co-block polymers. Solubility of SMV increased from 2 to 44-folds depending on co-block concentration with entrapment efficiency of 59%-80%. The NpM had size in the range of 206 to 402 nm with negative zeta potential. LA to GA ratio had greater effect on particle size reduction and increasing of co-polymer length. In addition, it had higher contributions on increasing of solubility and entrapment efficiency of SMV than PEG. Conclusion: According to these findings, the LA to GA ratio and PEG concentration gained a great consideration in order to prepare the PLGA-PEG-PLGA co-block which fulfilled the quality target product profile of NpM delivery system.

mPEG-PCL Nanoparticles as New Carriers for Delivery of a Prostae Cancer Drug Fluamide

2021 ◽  
pp. 3657-3661
Author(s):  
S. Venkateswara Rao ◽  
S. Sathesh Kumar
Keyword(s):  
Prostate Cancer ◽  
Particle Size ◽  
Zeta Potential ◽  
Surface Morphology ◽  
Targeted Delivery ◽  
Cancer Drug ◽  
23 Factorial Design ◽  
Nanoprecipitation Method ◽  
Poly Ethylene ◽  
Poly Caprolactone

The present work was aimed to prepare and evaluate Flutamide loaded methoxy poly (ethylene glycol) poly caprolactone (mPEG–PCL) nanoparticles for targeted delivery to the prostate cancer. The nanoparticles (NPs) were prepared by 23 factorial design and nanoprecipitation method. Various trials were evaluated for surface morphology, particle size and zeta potential. The influences of three formulation excipients such as polymer, stabilizer and organic phase volume on the characterization of NPs were investigated. The results of fourier transform infrared (FTIR) studies were indicated no interaction between the drug and polymer. The particle size varied from 79.2 to 89.1 nm and zeta potential value was found to be - 41.5 mv. The surface morphology of NPs was observed using scanning electron microscopy (SEM) and understands the arrangement and orientation of NPs to determine its behavior and stability. Flutamide loaded mPEG–PCL nanoparticle is a potential new carrier system for treatment of prostate cancer, which may overcome the problems associated with conventional formulations such as tablets.

scholarly journals Effect of Molecular Weight and Molar Ratio of Dextran on Self-Assembly of Dextran Stearate Polymeric Micelles as Nanocarriers for Etoposide

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Jaleh Varshosaz ◽  
Farshid Hassanzadeh ◽  
Hojjat Sadeghi ◽  
Farzin Firozian ◽  
Mina Mirian
Keyword(s):  
Molecular Weight ◽  
Particle Size ◽  
Zeta Potential ◽  
Self Assembly ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Molar Ratio ◽  
Loading Capacity ◽  
Hydrophobic Polymers ◽  
Polymer Surfactants

Amphiphilic polymer surfactants are composed of hydrophilic and hydrophobic polymers and are widely used in targeted drug delivery. The purpose of this study was the evaluation of the effect of molecular weight and molar ratio of dextran on physicochemical properties of dextran stearate polymeric micelles. Dextran stearate was synthesized by acylation of dextran with stearoyl chloride. Etoposide loaded polymeric micelles were prepared by dialysis method. The resulting micelles were evaluated for particle size, zeta potential, critical micelle concentration (CMC), drug loading capacity, and release efficiency. Cytotoxicity and cellular uptake of micelles were studied in CT-26 colorectal carcinoma cell line. Molecular weight and molar ratio of dextran-stearate were impressive on zeta potential, CMC, drug loading capacity, and release efficiency. Unlike polymer molecular weight, molar ratio of stearate had a significant effect on cytotoxicity and particle size of etoposide loaded micelles. Although molecular weight of dextran had no significant effect on cytotoxicity of micelles on CT-26 cells, it had drastic attributes for stability of polymeric micelles. Consequently, both variables of molecular weight of dextran and molar ratio of stearate should be taken into account to have a stable and effective micelle of dextran-stearate.

scholarly journals Green Synthesis of Polyherbal Silver Nanoparticles from Rosa Gallia officinalis, Citrus sinensis and Solanum tuberosum Extract for antioxidant Potency

2020 ◽  
Vol 11 (4) ◽  
pp. 6975-6985
Author(s):  
Brito Raj S ◽  
Boukary Obedoulaye ◽  
Sucharitha P ◽  
Saritha M ◽  
Shaheedha S M ◽  
...  
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Green Synthesis ◽  
Chemical Reduction ◽  
Radical Scavenging ◽  
Entrapment Efficiency ◽  
The Body ◽  
Free Radical Damage ◽  
Ic50 Values ◽  
Antioxidant Potency

Skin ageing is due to the combination of natural, largely genetically programmed and environmentally modulated changes which occur in the body system due to free radical damage. Silver Nanoparticle (AgNPs), were prepared by chemical reduction using green synthesis and they were evaluated for particle size in nanometer, zeta potential in millivolt, surface morphology by scanning electron microscopy (SEM) and percent entrapment efficiency. The polyphenols were quantified by chromatographic techniques and the antioxidant activity measured spectrophotometrically by DPPH (2,2 Diphenyl 1 picrylhydrazyl) assay. According to this study AgNPs showed a least particle size of 145.4±2.4nm, maximum zeta potential of -39.1±2.4 mV with desired polydispersity index of 0.358±0.02, the amount of polyphenols loaded in AgNPs was found to be 87.23±2.54%. Maximum phenolic content was found in F1 as 65.21 ± 3.721 mg equivalent GAE/g of extract. On comparing the IC50  values, F1 and F5 exhibited the lowest and highest values respectively. Therefore, F1 possesses higher DPPH radical scavenging potential.

scholarly journals The Interactions between Ciprofloxacin and Parenteral Nutrition Admixtures

Pharmaceutics ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 27 ◽  
Author(s):  
Aleksandra Gostyńska ◽  
Maciej Stawny ◽  
Katarzyna Dettlaff ◽  
Anna Jelińska
Keyword(s):  
Particle Size ◽  
Pulmonary Embolism ◽  
Zeta Potential ◽  
Parenteral Nutrition ◽  
Calcium Ions ◽  
Visual Inspection ◽  
Color Change ◽  
Molar Ratio ◽  
Fat Emulsion ◽  
Potential Interactions

Background: Co-infusion of parenteral nutrition (PN) and other drugs increases the risk of the interaction between drug and PN admixtures that can cause embolization of small blood vessels, resulting in potentially fatal consequences, including pulmonary embolism, or liver and retina vascular damage. The present study aimed to determine the compatibility between ciprofloxacin (CF) and eighteen compounded PN admixtures in order to assess the possibility of their co-administration via Y-sites. Methods: CF and PN admixtures were mixed at two volume ratios (1:1 and 2:1) and potential interactions were examined using visual inspection, and measurements of pH, osmolality particle size, and zeta potential. The analyses were conducted immediately after sample preparation and after four hours of storage. Results: The compatibility tests showed that the addition of the CF to the PN admixtures did not cause any color change or sign of destabilization in the fat emulsion. However, precipitation was observed in formulations containing higher CF concentrations and, in the case of lower CF concentrations, in formulations containing magnesium and calcium ions at a molar ratio of 2:1. Conclusions: The administration of CF and PN admixtures via the Y-site should be avoided or performed only with PN admixtures for which compatibility has been confirmed and the CF concentration in samples is 1 mg/mL at a molar ratio of magnesium to calcium ions of 1:1.

Incorporation of micro/nanoparticles of PCL with essential oil of Cymbopogon nardus in bacterial cellulose

2018 ◽  
Vol 1 (2) ◽  
pp. 37
Author(s):  
Aline Krindges ◽  
Vanusca Dalosto Jahno ◽  
Fernando Morisso
Keyword(s):  
Particle Size ◽  
Particulate Matter ◽  
Essential Oil ◽  
Zeta Potential ◽  
Bacterial Cellulose ◽  
Culture Medium ◽  
Static Culture ◽  
Cymbopogon Nardus ◽  
Cellulose Membranes

Incorporation studies of particles in different substrates with herbal assets growing. The objective of this work was the preparation and characterization of micro/nanoparticles containing cymbopogon nardus essential oil; and the incorporation of them on bacterial cellulose. For the development of the membranes was used the static culture medium and for the preparation of micro/nanoparticles was used the nanoprecipitation methodology. The incorporation of micro/nanoparticles was performed on samples of bacterial cellulose in wet and dry form. For the characterization of micro/nanoparticles were carried out analysis of SEM, zeta potential and particle size. For the verification of the incorporation of particulate matter in cellulose, analyses were conducted of SEM and FTIR. The results showed that it is possible the production and incorporation of micro/nanoparticles containing essential oil in bacterial cellulose membranes in wet form with ethanol.

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