scholarly journals Utilization of Gelling Polymer to Formulate Nanoparticles Loaded with Epalrestat-Cyclodextrin Inclusion Complex: Formulation, Characterization, In-Silico Modelling and In-Vivo Toxicity Evaluation

Polymers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 4350
Author(s):  
Zunaira Alvi ◽  
Muhammad Akhtar ◽  
Nisar U. Rahman ◽  
Khaled M. Hosny ◽  
Amal M. Sindi ◽  
...  
Keyword(s):  
In Silico ◽  
Sodium Tripolyphosphate ◽  
Polymeric Nanoparticles ◽  
Chitosan Nanoparticles ◽  
Chemical Properties ◽  
Aqueous Solubility ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Cross Linker

Epalrestat (EPL) is an aldose reductase inhibitor with poor aqueous solubility that affects its therapeutic efficacy. The research study was designed to prepare epalrestat-cyclodextrins (EPL-CDs) inclusion complexes to enhance the aqueous solubility by using beta-cyclodextrin (β-CD) and sulfobutyl ether₇ β-CD (SBE7 β-CD). Furthermore, polymeric nanoparticles (PNPs) of EPL-CDs were developed using chitosan (CS) and sodium tripolyphosphate (sTPP). The EPL-CDs complexed formulations were then loaded into chitosan nanoparticles (CS NPs) and further characterized for different physico-chemical properties, thermal stability, drug-excipient compatibility and acute oral toxicity studies. In-silico molecular docking of cross-linker with SBE7 β-CD was also carried out to determine the binding site of the CDs with the cross-linker. The sizes of the prepared NPs were laid in the range of 241.5–348.4 nm, with polydispersity index (PDI) ranging from 0.302–0.578. The surface morphology of the NPs was found to be non-porous, smooth, and spherical. The cumulative percentage of drug release from EPL-CDs loaded CS NPs was found to be higher (75–88%) than that of the pure drug (25%). Acute oral toxicity on animal models showed a biochemical, histological profile with no harmful impact at the cellular level. It is concluded that epalrestat-cyclodextrin chitosan nanoparticles (EPL-CDs-CS NPs) with improved solubility are safe for oral administration since no toxicity was reported on vital organs in rabbits.

scholarly journals A New Symmetrical Thiazolidinedione Derivative: In Silico Design, Synthesis, and In Vivo Evaluation on a Streptozotocin- Induced Rat Model of Diabetes

Processes ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1294
Author(s):  
Samuel Álvarez-Almazán ◽  
Gabriel Navarrete-Vázquez ◽  
Itzia Irene Padilla-Martínez ◽  
José Correa-Basurto ◽  
Diana Alemán-González-Duhart ◽  
...  
Keyword(s):  
Rat Model ◽  
In Silico ◽  
Female Rats ◽  
Therapeutic Effects ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
In Vivo Evaluation ◽  
Docking Simulations ◽  
Ppar Γ

By activating PPAR-γ, thiazolidinediones normalize glucose levels in animal models of type 2 diabetes and in patients with this pathology. The aim of the present study was to analyze 219 new derivatives in silico and select the best for synthesis, to be evaluated for acute oral toxicity in female rats and for control of diabetes-related parameters in a rat model of streptozotocin-induced diabetes. The best compound was chosen based on pharmacokinetic, pharmacodynamic, and toxicological parameters obtained in silico and binding orientation observed by docking simulations on PPAR-γ. Compound 1G was synthesized by a quick and easy Knoevenagel condensation. Acute oral toxicity was found at a dose greater than 2000 mg/Kg. Compound 1G apparently produces therapeutic effects similar to those of pioglitazone, decreasing glycaemia and triglyceride levels in diabetic animals, without liver damage. Moreover, it did not cause a significant weight gain and tended to reduce polydipsia and polyphagia, while diminishing systemic inflammation related to TNF-α and IL-6. It lowered the level of endogenous antioxidant molecules such as reduced glutathione and glutathione reductase. In conclusion, 1G may be a candidate for further testing as an euglycemic agent capable of preventing the complications of diabetes.

Ruthenium Complexes for 1- and 2-Photon Photodynamic Therapy: From In Silico Prediction to In Vivo Applications

2020 ◽  
Author(s):  
Johannes Karges ◽  
Shi Kuang ◽  
Federica Maschietto ◽  
Olivier Blacque ◽  
Ilaria Ciofini ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
In Silico ◽  
Aqueous Solubility ◽  
The Body ◽  
Photon Absorption ◽  
Multicellular Tumor Spheroids ◽  
Spectral Window ◽  
Photon Excitation ◽  
Polypyridine Complexes

<div>The use of photodynamic therapy (PDT) against cancer has received increasing attention overthe recent years. However, the application of the currently approved photosensitizers (PSs) is somehow limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E’)-4,4´-bisstyryl 2,2´-bipyridine ligands showed impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While non-toxic in the dark, these compounds were found phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and be able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2 Photon excitation.</div>

Sub-acute oral toxicity and in vivo antioxidant properties of Oxalis cernua

2020 ◽  
Vol 133 ◽  
pp. 91-97
Author(s):  
Meriama Belghoul ◽  
Abderrahmane Baghiani ◽  
Seddik Khennouf ◽  
Lekhmici Arrar
Keyword(s):  
Antioxidant Properties ◽  
Acute Oral Toxicity ◽  
Oral Toxicity

scholarly journals Ionically Cross-Linked Chitosan Nanoparticles for Sustained Delivery of Docetaxel: Fabrication, Post-Formulation and Acute Oral Toxicity Evaluation

2019 ◽  
Vol Volume 14 ◽  
pp. 10035-10046 ◽  
Author(s):  
Muhammad Ahmad Mahmood ◽  
Asadullah Madni ◽  
Mubashar Rehman ◽  
Muhammad Abdur Rahim ◽  
Abdul Jabar
Keyword(s):  
Chitosan Nanoparticles ◽  
Sustained Delivery ◽  
Acute Oral Toxicity ◽  
Toxicity Evaluation ◽  
Oral Toxicity

scholarly journals How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 675 ◽  
Author(s):  
Mariana Amaral ◽  
Ana Sofia Martins ◽  
José Catarino ◽  
Pedro Faísca ◽  
Pradeep Kumar ◽  
...  
Keyword(s):  
In Silico ◽  
Ex Vivo ◽  
Polymeric Nanoparticles ◽  
Spherical Shape ◽  
Diabetic Rats ◽  
Laser Scattering ◽  
In Vivo Models ◽  
Mean Size

Currently, insulin can only be administered through the subcutaneous route. Due to the flaws associated with this route, it is of interest to orally deliver this drug. However, insulin delivered orally has several barriers to overcome as it is degraded by the stomach’s low pH, enzymatic content, and poor absorption in the gastrointestinal tract. Polymers with marine source like chitosan are commonly used in nanotechnology and drug delivery due to their biocompatibility and special features. This work focuses on the preparation and characterization of mucoadhesive insulin-loaded polymeric nanoparticles. Results showed a suitable mean size for oral administration (<600 nm by dynamic laser scattering), spherical shape, encapsulation efficiency (59.8%), and high recovery yield (80.6%). Circular dichroism spectroscopy demonstrated that protein retained its secondary structure after encapsulation. Moreover, the mucoadhesive potential of the nanoparticles was assessed in silico and the results, corroborated with ex-vivo experiments, showed that using chitosan strongly increases mucoadhesion. Besides, in vitro and in vivo safety assessment of the final formulation were performed, showing no toxicity. Lastly, the insulin-loaded nanoparticles were effective in reducing diabetic rats’ glycemia. Overall, the coating of insulin-loaded nanoparticles with chitosan represents a potentially safe and promising approach to protect insulin and enhance peroral delivery.

scholarly journals In Vivo Wound Healing Activity of Abrus cantoniensis Extract

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Qi Zeng ◽  
Hui Xie ◽  
Hongjin Song ◽  
Fayu Nie ◽  
Jiahua Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chemical Constituents ◽  
Blood Stasis ◽  
Acute Oral Toxicity ◽  
Test Results ◽  
Dermal Toxicity ◽  
Oral Toxicity ◽  
Incision Wound ◽  
Wound Healing Activity

Abrus cantoniensis (Leguminosae sp.) is a traditionally used remedy for treating rheumatism, blood stasis, and internal injuries. In order to reveal a new insight of the utilization of the plant, solvent extraction by ethyl acetate (EA) was performed in order to evaluate the plant extracts’ in vivo excision and incision-wound potentials with models. The contents of the EA fraction, wound healing activity, acute oral toxicity, and acute dermal toxicity were studied. As a result, the main chemical constituents of the EA fraction were alkaloids, flavonoids, and steroids. The acute oral toxicity test results and assessment of skin hypoallergenicity showed that the plant extract was safe at LD50 as high as 5000 mg/kg. Both excision and incision model tests results indicated that the EA fraction of A. cantoniensis showed a significant wound healing capacity at a concentration of 5% (v/w) (p<0.01) as observed by the increased wound contraction, decreased epithelialization time, and increased hydroxyproline content compared to the ones of the controls. The present study showed that the EA fraction of A. cantoniensis possesses potential wound healing activities and provided recent results for the use of A. cantoniensis for wound curing.

scholarly journals A sub-acute oral toxicity analysis and comparative in vivo anti-diabetic activity of zinc oxide, cerium oxide, silver nanoparticles, and Momordica charantia in streptozotocin-induced diabetic Wistar rats

RSC Advances ◽  
2017 ◽  
Vol 7 (59) ◽  
pp. 37158-37167 ◽  
Author(s):  
Kalakotla Shanker ◽  
Jayarambabu Naradala ◽  
G. Krishna Mohan ◽  
G. S. Kumar ◽  
P. L. Pravallika
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Silver Nanoparticles ◽  
Wistar Rats ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Toxicity Analysis ◽  
P Type

Type 2 diabetes mellitus (T2DM) is one of the most threatening, non-communicable ailments worldwide.

scholarly journals Chitosan Nanoparticles at the Biological Interface: Implications for Drug Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1686
Author(s):  
Noorjahan Aibani ◽  
Raj Rai ◽  
Parth Patel ◽  
Grace Cuddihy ◽  
Ellen K. Wasan
Keyword(s):  
Drug Delivery ◽  
Cellular Uptake ◽  
Chitosan Nanoparticles ◽  
Chemical Properties ◽  
Protein Corona ◽  
Systemic Circulation ◽  
Systemic Delivery ◽  
Toxicological Evaluation ◽  
Wide Range

The unique properties of chitosan make it a useful choice for various nanoparticulate drug delivery applications. Although chitosan is biocompatible and enables cellular uptake, its interactions at cellular and systemic levels need to be studied in more depth. This review focuses on the various physical and chemical properties of chitosan that affect its performance in biological systems. We aim to analyze recent research studying interactions of chitosan nanoparticles (NPs) upon their cellular uptake and their journey through the various compartments of the cell. The positive charge of chitosan enables it to efficiently attach to cells, increasing the probability of cellular uptake. Chitosan NPs are taken up by cells via different pathways and escape endosomal degradation due to the proton sponge effect. Furthermore, we have reviewed the interaction of chitosan NPs upon in vivo administration. Chitosan NPs are immediately surrounded by a serum protein corona in systemic circulation upon intravenous administration, and their biodistribution is mainly to the liver and spleen indicating RES uptake. However, the evasion of RES system as well as the targeting ability and bioavailability of chitosan NPs can be improved by utilizing specific routes of administration and covalent modifications of surface properties. Ongoing clinical trials of chitosan formulations for therapeutic applications are paving the way for the introduction of chitosan into the pharmaceutical market and for their toxicological evaluation. Chitosan provides specific biophysical properties for effective and tunable cellular uptake and systemic delivery for a wide range of applications.

scholarly journals Control of Anthracnose Disease (Colletotrichum gloeosporioides) Using Nano Chitosan Hydrolyzed by Chitinase Derived from Burkholderia cepacia Isolate E76

2018 ◽  
Vol 13 (2) ◽  
pp. 111 ◽  
Author(s):  
Yadi Suryadi ◽  
Tri Puji Priyatno ◽  
I Made Samudra ◽  
Dwi Ningsih Susilowati ◽  
Tuti Septi Sriharyani ◽  
...  
Keyword(s):  
Burkholderia Cepacia ◽  
Colletotrichum Gloeosporioides ◽  
Sodium Tripolyphosphate ◽  
Average Particle Size ◽  
Chitosan Nanoparticles ◽  
Average Particle ◽  
Coating Application ◽  
Anthracnose Disease

<p>Anthracnose (Colletotrichum gloeosporioides) is one of the important diseases of fruit crops that need to be controlled. This study was aimed to obtain the best formula of hydrolyzed nano chitosan and its potensial in controlling anthracnose. The hydrolyzed chitosan was prepared using chitinase enzyme extracted from Burkholderia cepacia isolate E76. Chitosan nanoparticles were synthesized using ionic gelation method by reacting hydrolyzed chitosan (0.2%) with Sodium tripolyphosphate (STPP) (0.1%) as cross-linking agent using 30&amp;ndash;60 minutes stirring condition. The bioactivity of the nano chitosan formula was tested to C. gloeosporioides under in vitro and in vivo assays. The specific enzymatic activity of the purified chitinase was higher (0.19 U/mg) than that of crude enzyme (supernatant) with the purity increased by 3.8 times. Of the four formula tested, Formula A (hydrolyzed chitosan to STPP volume ratio of 5 : 1 with 60 minutes stirring condition) was found good in terms of physical characteristic of the particle. The formula nano chitosan particle had the spherical-like shape with an average particle size of 126.2+3.8 nm, polydispersity index (PI) of 0.4+0.02, and zeta potential (ZP) value of 27.8+0.2 mV. Nano chitosan had an inhibitory activity to C. gloeosporioides in vitro up to 85.7%. Moreover, it could inhibit 61.2% of C. gloeosporioides spores germination. It was shown that nano chitosan was also effective to reduce anthracnose disease severity in vivo when applied as a preventive measure on chili and papaya fruits. This study could be used as a reference for further fruit coating application using nano chitosan as a promising postharvest biocontrol agent to C. gloeosporioides.</p>

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