scholarly journals ROS-responsive biomimetic nanoparticles for potential application in targeted anti-atherosclerosis

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Dan Tang ◽  
Yi Wang ◽  
Andy Wijaya ◽  
Boyan Liu ◽  
Ali Maruf ◽  
...  
Keyword(s):  
Drug Release ◽  
Potential Application ◽  
Critical Role ◽  
Potential Candidate ◽  
Biomimetic Nanoparticles ◽  
Negative Surface ◽  
Negative Surface Charge ◽  
High Reactive Oxygen Species

Abstract The development of nanomedicines provides new opportunities for the treatment of atherosclerosis (AS) due to their great advantages such as the improved drug solubility, enhanced bioavailability and reduced side effects. Despite these advantages, nanomedicines are still facing some challenges. The problems remain in the short circulation life, lack of specific targeting and poor drug release controllability. In order to overcome the shortages of conventional nanomedicines, the combination of biomimetic strategy with smart nanoagents has been proposed. In light with the high reactive oxygen species (ROS) level in AS microenvironment and the fact that macrophages play a critical role in the pathogenesis of AS, we fabricated ROS-responsive biomimetic nanoparticles (NPs), which camouflaged macrophage membrane (MM) on ROS-responsive NPs loaded with rapamycin (RNPs) for potential application in AS therapy. The resulting ROS-responsive biomimetic NPs (MM/RNPs) exhibited favorable hydrodynamic size with negative surface charge, retained the functional proteins from MM, and showed ROS-responsive drug release. Because of the biomimetic camouflaging on surface, MM/RNPs could effectively escape from macrophages uptake and target to inflammatory endothelial cells. Meanwhile, MM/RNPs could inhibit the proliferation of macrophages and smooth muscle cells in vitro. Furthermore, the MM-coated NPs were found to be nontoxic in both cytotoxicity assay and in vivo toxicity evaluation. Consequently, these results demonstrated that MM/RNPs could be a potential candidate of drug delivery system for safe and effective anti-AS applications.

scholarly journals Nanogels of Succinylated Glycol Chitosan-Succinyl Prednisolone Conjugate: Preparation, In Vitro Characteristics and Therapeutic Potential

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 333 ◽  
Author(s):  
Zhou ◽  
Ichikawa ◽  
Ikeuchi-Takahashi ◽  
Hattori ◽  
Onishi
Keyword(s):  
Therapeutic Potential ◽  
Trinitrobenzene Sulfonic Acid ◽  
Glycol Chitosan ◽  
In Vivo Evaluation ◽  
Drug Effectiveness ◽  
Thymus Atrophy ◽  
Negative Surface ◽  
Negative Surface Charge

A novel anionic nanogel system was prepared using succinylated glycol chitosan-succinyl prednisolone conjugate (S-GCh-SP). The nanogel, named NG(S), was evaluated in vitro and in vivo. S-GCh-SP formed a nanogel via the aggregation of hydrophobic prednisolone (PD) moieties and the introduced succinyl groups contributed to the negative surface charge of the nanogel. The resultant NG(S) had a PD content of 13.7% (w/w), was ca. 400 nm in size and had a -potential of −28 mV. NG(S) released PD very slowly at gastric pH and faster but gradually at small intestinal pH. Although NG(S) was easily taken up by the macrophage-like cell line Raw 264.7, it did not decrease cell viability, suggesting that the toxicity of the nanogel was very low. The in vivo evaluation was performed using rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis. NG(S) and PD alone were not very effective at 5 mg PD eq./kg. However, NG(S) at 10 mg PD eq./kg markedly suppressed colonic damage, whereas PD alone did not. Furthermore, thymus atrophy was less with NG(S) than with PD alone. These results demonstrated that NG(S) is very safe, promotes drug effectiveness and has low toxicity. NG(S) has potential as a drug delivery system for the treatment of ulcerative colitis.

Surface charge of insect haemocytes, examined using cell electrophoresis and cationized ferritin-binding

1985 ◽  
Vol 75 (1) ◽  
pp. 207-214
Author(s):  
G. Takle ◽  
A.M. Lackie
Keyword(s):  
Surface Charge ◽  
Periplaneta Americana ◽  
Schistocerca Gregaria ◽  
Cationized Ferritin ◽  
Cell Electrophoresis ◽  
Insect Haemocytes ◽  
Negative Surface ◽  
Negative Surface Charge

Differences in the negative surface charge of haemocytes from Periplaneta americana and Schistocerca gregaria have been revealed using cell electrophoresis and cationized ferritin-binding. Although haemocyte populations from both insect species exhibit ranges of negative surface charge, both techniques show that Schistocerca haemocytes are significantly more negative than Periplaneta haemocytes. The results may help to explain why Schistocerca haemocytes adhere poorly to negative substrata, both in vitro and in vivo, and suggest that an electrostatic mechanism may be involved, at least in part, in adhesion of insect haemocytes to substrata.

scholarly journals Protection Induced By Ginsenoside Rb1 in Alzheimer’s Disease Model is Associated With Redressing The Neuronal Hyperexcitability Which is Regulated By Nav1.2 and Nav1.6

2021 ◽  
Author(s):  
shan li ◽  
Min-Nan Lu ◽  
Qian Wang ◽  
Yun Yuan ◽  
Xiao-Min Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuroprotective Effect ◽  
Critical Role ◽  
Potential Candidate ◽  
Protective Effects ◽  
Ginsenoside Rb1 ◽  
Patch Clamp Recording

Abstract Background: Alzheimer’s disease (AD), a neurodegenerative disease showing multiple complex pathomechanism alterations, has affected the normal life of many old people. It is urgent to find an effective medicine for AD. Ginsenoside Rb1 (Rb1) is the main component of panax notoginseng saponins, a famous Chinese herbal medicine, and is expected to be a useful drug in the treatment of AD. This study mainly explored the potential effects of Rb1 in model of AD in vivo and in vitro, and investigated the possible mechanisms. Materials and methods: We studied the neuroprotective effect of Rb1 in transgenic mouse animal model and cell AD model in vitro. The cognitive function of APP/PS1 mice was measured in Morris water maze and Novel Object Recognition. Electrophysiological patch clamp recording and electrophysiology were used to nerve excitability. Further, the expression of proteins of Nav1.2 and Nav1.6 were used by Western blot. Results: We found that Rb1 treatment significantly improved the cognitive and memory loss, and reversed the hyperexcitability by altering the expressions of Nav1.2 and Nav1.6 of APP/PS1 mice. Further, Rb1 improved the hyperexcitability induced by Aβ1-42-injured neurons, which might be associated with alteration of the expressions of Nav1.2 and Nav1.6. As we expect, Rb1 attenuated Aβ1-42-induced injury in primary neurons. Conclusion: Our data showed that Rb1 played a critical role in improvement of the cognitive deficit and abnormal excitability of AD by regulating Nav1.2 and Nav1.6 expressions. Thus, Rb1 shows protective effects on AD models and may be a potential candidate for AD treatment.

Poly I:C-based rHBVvac therapeutic vaccine eliminates HBV via generation of HBV-specific CD8+ effector memory T cells

Gut ◽  
2019 ◽  
Vol 68 (11) ◽  
pp. 2032-2043 ◽  
Author(s):  
Hua-Jun Zhao ◽  
Qiu-Ju Han ◽  
Guan Wang ◽  
Ang Lin ◽  
Dong-Qing Xu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Critical Role ◽  
Therapeutic Vaccine ◽  
Poly I:C ◽  
Effector Memory ◽  
Potential Candidate

ObjectiveChronic hepatitis B (CHB) virus infection is a global health problem. Finding a cure for CHB remains a challenging task.DesignIn this study, poly I:C was employed as an adjuvant for HBV therapeutic vaccine (referred to as pHBV-vaccine) and the feasibility and efficiency of pHBV-vaccine in CHB treatment were evaluated in HBV-carrier mice.ResultsWe found that pHBV-vaccine decreased HBsAg and HBV DNA efficiently and safely in HBV-carrier mice. Further investigation showed that pHBV-vaccine promoted maturation and antigen presentation ability of dendritic cells in vivo and in vitro. This vaccine successfully restored the exhaustion of antigen-specific CD8+ T cells and partly broke the immune tolerance established in HBV-carrier mice. pHBV-vaccine also enhanced the proliferation and polyfunctionality of HBV-specific CD11ahi CD8αlo cells. Importantly, we observed that T cell activation molecule KLRG1 was only expressed on HBV specific CD11ahi CD8αlo cells. Furthermore, pHBV-vaccine reduced the expression of Eomes and increased the serum IL-12 levels, which in turn promoted the generation of effector memory short-lived effector cells (SLECs) to exhibit a critical role in HBV clearance. SLECs induced by pHBV-vaccine might play a crucial role in protecting from HBV reinfection.ConclusionsFindings from this study provide a new basis for the development of therapeutic pHBV-vaccine, which might be a potential candidate for clinical CHB therapy.

Study on the Slow-release Mometasone Furoate Injection of PLGA for the Treatment of Knee Arthritis

2020 ◽  
Vol 17 ◽  
Author(s):  
Yutong Liang ◽  
Jiaojiao Zhang ◽  
Xinghua Zhao ◽  
Ming Wang ◽  
Shi Ding ◽  
...  
Keyword(s):  
Drug Release ◽  
Encapsulation Efficiency ◽  
Safety Evaluation ◽  
Mometasone Furoate ◽  
Pharmacokinetic Data ◽  
Potential Candidate ◽  
Water Emulsion

Purpose: The purpose of this study is to develop a new PLGA based formulation for microspheres, which aims to release mometasone furoate for one month, so as to improve compliance. Methods: The microspheres containing mometasone furoate were prepared by oil in water emulsion and solvent evaporation. The microspheres were characterized by surface morphology, shape, size and encapsulation efficiency. The release in vitro was studied in 37°C phosphate buffer, and in vivo, pharmacodynamics and preliminary safety evaluation were conducted in male Sprague Dawley rats. Results: The morphology results show that the microspheres have smooth surface, spherical shape and the average diameter of 2.320-5.679μm. The encapsulation efficiency of the microspheres loaded with mometasone furoate is in the range of 53.1% to 95.2%, and the encapsulation efficiency of the microspheres can be greatly affected by the proportion of oil phase to water phase and other formulation parameters. In vitro release kinetics revealed that drug release from microspheres was through non Fick's diffusion and PLGA polymer erosion. Pharmacokinetic data showed that the initial release of microspheres was small and then sustained. The results of pharmacodynamic study fully proved the effectiveness and long-term effect of mometasone furoate microspheres. The results of in vivo safety evaluation showed that the preparation system had good in vivo safety. Conclusion: This study shows that the microspheres prepared in this study have sufficient ability of stable drug release at least 35 days, with good efficacy and high safety. In addition, mometasone furoate can be used as a potential candidate drug for 35 day long-term injection.

Preparation and Evaluation of Gemifloxacin Mesylate Floating Matrix Tablets in Healthy Human Volunteers

2017 ◽  
Vol 10 (1) ◽  
pp. 3623-3630
Author(s):  
Bhikshapathi D. V. R. N. ◽  
Haarika B ◽  
Jyothi Sri S ◽  
K Abbulu
Keyword(s):  
Drug Release ◽  
Sodium Bicarbonate ◽  
Polymer Concentration ◽  
Hydroxypropyl Methylcellulose ◽  
Matrix Tablets ◽  
Physical Parameters ◽  
Drug Bioavailability ◽  
Floating Tablets

The purpose of present investigation was to develop floating matrix tablets of gemifloxacin mesylate, which after oral administration could prolong the gastric residence time, increase the drug bioavailability and diminish the side effects of irritating drugs. Tablets containing drug, various viscosity grades of hydroxypropyl methylcellulose such as HPMC K4M and HPMC K15M as matrix forming agent, Sodium bicarbonate as gas-forming agent and different additives were tested for their usefulness in formulating gastric floating tablets by direct compression method. The physical parameters, in vitro buoyancy, release characteristics and in vivo radiographic study were investigated in this study. The gemifloxacin mesylate floating tablets were prepared using HPMC K4M polymer giving more sustained drug release than the tablet containing HPMC K15M. All these formulations showed floating lag time of 30 to 47 sec and total floating time more than 12 h. The drug release was decreased when polymer concentration increases and gas generating agent decreases. Formulation that contains maximum concen-tration of both HPMC K15M and sodium bicarbonate (F9) showing sufficiently sustained with 99.2% of drug release at 12 h. The drug release from optimized formulation follows Higuchi model that indicates the diffusion controlled release. The best formulation (F9) was selected based on in vitro characteristics and used in vivo radiographic studies by incorporating barium sulphate as a radio-opaque agent and the tablet remained in the stomach for about 6 h.   

Design and In vivo Evaluation of Palonosetron HCl Mouth Dissolving Films in the Management of Chemotherapy-Induced Vomiting

2017 ◽  
Vol 10 (6) ◽  
pp. 3929-3936
Author(s):  
Y. Srinivasa Rao ◽  
K. Adinarayana Reddy
Keyword(s):  
Drug Release ◽  
Patient Compliance ◽  
Onset Of Action ◽  
In Vivo Evaluation ◽  
Disintegration Time ◽  
In Vitro Drug Release ◽  
Surface Ph ◽  
Drug Content

Fast dissolving oral delivery systems are solid dosage forms, which disintegrate or dissolve within 1 minute in the mouth without drinking water or chewing. Mouth dissolving film (MDF) is a better alternate to oral disintegrating tablets due to its novelty, ease of use and the consequent patient compliance. The purpose of this work was to develop mouth dissolving oral films of palonosetron HCl, an antiemetic drug especially used in the prevention and treatment of chemotherapy-induced nausea and vomiting. In the present work, the films were prepared by using solvent casting method with various polymers HPMC E3, E5 & E15 as a film base synthetic polymer, propylene glycol as a plasticizer and maltodextrin and other polymers. Films were found to be satisfactory when evaluated for thickness, in vitro drug release, folding endurance, drug content and disintegration time. The surface pH of all the films was found to be neutral. The in vitro drug release of optimized formulation F29 was found to be 99.55 ± 6.3 7% in 7 min. The optimized formulation F29 also showed satisfactory surface pH, drug content (99.38 ± 0.08 %), disintegration time of 8 seconds and good stability. FTIR data revealed that no interaction takes place between the drug and polymers used in the optimized formulation. In vitro and in vivo evaluation of the films confirmed their potential as an innovative dosage form to improve delivery and quick onset of action of Palonosetron Hydrochloride. Therefore, the mouth dissolving film of palonosetron is potentially useful for the treatment of emesis disease where quick onset of action is desired, also improved patient compliance.

Formulation and In Vivo Evaluation of Mucoadhesive Micro-spheres of Rebamipide, a Mucoprotective Drug for GIT Disorders

2018 ◽  
Vol 11 (3) ◽  
pp. 4089-4097
Author(s):  
Bhikshapathi D. V. R. N. ◽  
Kanteepan P
Keyword(s):  
Drug Release ◽  
Entrapment Efficiency ◽  
In Vivo Studies ◽  
Amino Acid Derivative ◽  
Release Mechanism ◽  
In Vivo Evaluation ◽  
In Vitro Drug Release ◽  
Percentage Yield

Rebamipide, an amino acid derivative of 2-(1H)-quinolinone, is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. The current research study aimed to develop novel gastro-retentive mucoadhesive microspheres of rebamipide using ionotropic gelation technique. Studies of micromeritic properties confirmed that microspheres were free flowing with good packability. The in vitro drug release showed the sustained release of rebamipide up to 99.23 ± 0.13% within 12 h whereas marketed product displayed the drug release of 95.15 ± 0.23% within 1 h. The release mechanism from microspheres followed the zero-order and Korsmeyer-Peppas (R2 = 0.915, 0.969), respectively. The optimized M12 formulation displayed optimum features, such as entrapment efficiency 97%, particle size 61.94 ± 0.11 µm, percentage yield 98%, swelling index 95% and mucoadhesiveness was 97%. FTIR studies revealed no major incompatibility between drug and excipients. SEM confirmed the particles were of spherical in shape. Optimized formulation (M12) were stable at 40°C ± 2°C/75% RH ± 5% RH for 6 months. In vivo studies were performed and kinetic parameters like Cmax, Tmax, AUC0-t, AUC0-∞, t1/2, and Kel  were calculated. The marketed product Cmax (3.15 ± 0.05 ng/mL) was higher than optimized formulation (2.58 ± 0.03 ng/mL). The optimized formulation AUC0-t (15.25 ± 1.14 ng.hr/mL), AUC0-∞ (19.42 ± 1.24 ng.hr/mL) was significantly higher than that of marketed product AUC0-t (10.21 ± 1.26 ng.hr/mL) and AUC0-∞ (13.15 ± 0.05 ng.hr/mL). These results indicate an optimized formulation bioavailability of 2.5-fold greater than marketed product.  

Synthesis, Characterization and in vivo Evaluation of PEGylated PPI Dendrimer for Safe and Prolonged Delivery of Insulin

2019 ◽  
Vol 9 (3) ◽  
pp. 248-263 ◽  
Author(s):  
Ashish K. Parashar ◽  
Preeti Patel ◽  
Arun K. Gupta ◽  
Neetesh K. Jain ◽  
Balak Das Kurmi
Keyword(s):  
Blood Glucose ◽  
Drug Release ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Albino Rats ◽  
Sustained Delivery ◽  
In Vivo Evaluation ◽  
Hemolytic Toxicity

Background: The present study was aimed at developing and exploring the use of PEGylated Poly (propyleneimine) dendrimers for the delivery of an anti-diabetic drug, insulin. Methods: For this study, 4.0G PPI dendrimer was synthesized by successive Michael addition and exhaustive amidation reactions, using ethylenediamine as the core and acrylonitrile as the propagating agent. Two different activated PEG moieties were employed for PEGylation of PPI dendrimers. Various physicochemical and physiological parameters UV, IR, NMR, TEM, DSC, drug entrapment, drug release, hemolytic toxicity and blood glucose level studies of both PEGylated and non- PEGylated dendritic systems were determined and compared. Results: PEGylation of PPI dendrimers caused increased solubilization of insulin in the dendritic framework as well as in PEG layers, reduced drug release and hemolytic toxicity as well as increased therapeutic efficacy with reduced side effects of insulin. These systems were found to be suitable for sustained delivery of insulin by in vitro and blood glucose-level studies in albino rats, without producing any significant hematological disturbances. Conclusion: Thus, surface modification of PPI dendrimers with PEG molecules has been found to be a suitable approach to utilize it as a safe and effective nano-carrier for drug delivery.

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