scholarly journals Fabrication and Biological Assessment of Antidiabetic α-Mangostin Loaded Nanosponges: In Vitro, In Vivo, and In Silico Studies

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6633
Author(s):  
Faisal Usman ◽  
Hamid Saeed Shah ◽  
Sumera Zaib ◽  
Sirikhwan Manee ◽  
Jahanzeb Mudassir ◽  
...  
Keyword(s):  
Microvascular Complications ◽  
Treatment Strategies ◽  
Biological Assessment ◽  
In Vivo Studies ◽  
Hydrodynamic Diameter ◽  
Scanning Calorimetry ◽  
Ligand Complex ◽  
In Silico Studies

Type 2 diabetes mellitus has been a major health issue with increasing morbidity and mortality due to macrovascular and microvascular complications. The urgent need for improved methods to control hyperglycemic complications reiterates the development of innovative preventive and therapeutic treatment strategies. In this perspective, xanthone compounds in the pericarp of the mangosteen fruit, especially α-mangostin (MGN), have been recognized to restore damaged pancreatic β-cells for optimal insulin release. Therefore, taking advantage of the robust use of nanotechnology for targeted drug delivery, we herein report the preparation of MGN loaded nanosponges for anti-diabetic therapeutic applications. The nanosponges were prepared by quasi-emulsion solvent evaporation method. Physico-chemical characterization of formulated nanosponges with satisfactory outcomes was performed with Fourier transform infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Zeta potential, hydrodynamic diameter, entrapment efficiency, drug release properties, and stability studies at stress conditions were also tested. Molecular docking analysis revealed significant interactions of α-glucosidase and MGN in a protein-ligand complex. The maximum inhibition by nanosponges against α-glucosidase was observed to be 0.9352 ± 0.0856 µM, 3.11-fold higher than acarbose. In vivo studies were conducted on diabetic rats and plasma glucose levels were estimated by HPLC. Collectively, our findings suggest that MGN-loaded nanosponges may be beneficial in the treatment of diabetes since they prolong the antidiabetic response in plasma and improve patient compliance by slowly releasing MGN and requiring less frequent doses, respectively.

Recent In Vitro and In Silico Advances in the Understanding of Intranasal Drug Delivery

2020 ◽  
Vol 26 ◽  
Author(s):  
John Chen ◽  
Andrew Martin ◽  
Warren H. Finlay
Keyword(s):  
Drug Delivery ◽  
In Silico ◽  
Local Drug Delivery ◽  
In Vivo Studies ◽  
Intranasal Drug Delivery ◽  
Nasal Sprays ◽  
In Silico Studies ◽  
Drug Delivery Devices

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Because of the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: To perform a summary of advances in understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers are able to more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on Possible Correlation

2018 ◽  
Vol 21 (3) ◽  
pp. 215-221
Author(s):  
Haroon Khan ◽  
Muhammad Zafar ◽  
Helena Den-Haan ◽  
Horacio Perez-Sanchez ◽  
Mohammad Amjad Kamal
Keyword(s):  
In Silico ◽  
Docking Studies ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Chronic Obstructive ◽  
Lipoxygenase Inhibitors ◽  
Lipoxygenase Inhibition ◽  
In Silico Studies

Aim and Objective: Lipoxygenase (LOX) enzymes play an important role in the pathophysiology of several inflammatory and allergic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are believed to be an ideal approach in the treatment of diseases caused by its over-expression. In this regard, several synthetic and natural agents are under investigation worldwide. Alkaloids are the most thoroughly investigated class of natural compounds with outstanding past in clinically useful drugs. In this article, we have discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with possible correlation in in silico studies. Materials and Methods: Molecular docking studies were performed using MOE (Molecular Operating Environment) software. Among the ten reported LOX alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed excellent docking scores and receptor sensitivity. Result and Conclusion: These compounds already exhibited in vitro lipoxygenase inhibition and the MOE results strongly correlated with the experimental results. On the basis of these in vitro assays and computer aided results, we suggest that these compounds need further detail in vivo studies and clinical trial for the discovery of new more effective and safe lipoxygenase inhibitors. In conclusion, these results might be useful in the design of new and potential lipoxygenase (LOX) inhibitors.

scholarly journals Melt-Cast Films Significantly Enhance Triamcinolone Acetonide Delivery to the Deeper Ocular Tissues

Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 158
Author(s):  
Akshaya Tatke ◽  
Narendar Dudhipala ◽  
Karthik Janga ◽  
Bhavik Soneta ◽  
Bharathi Avula ◽  
...  
Keyword(s):  
Triamcinolone Acetonide ◽  
Polymer Matrix ◽  
Rabbit Model ◽  
In Vivo Studies ◽  
Invasive Technique ◽  
Content Uniformity ◽  
Scanning Calorimetry ◽  
Ocular Tissues

Delivering an effective drug load to the posterior section of the ocular tissues, while using a non-invasive technique, has always been a challenge. In this regard, the goal of the present study was to develop sustained release triamcinolone acetonide (TA) loaded polymeric matrix films for ocular delivery. The TA-films were prepared in two different polymer matrices, with drug loadings of 10% and 20% w/w, and they were evaluated for ocular distribution in vivo in a conscious rabbit model. A 4% w/v TA suspension (TA-C) was used as a control for in vitro and in vivo studies. The TA-films, prepared with melt-cast technology, used polyethylene oxide (PEO) and Soluplus® as the polymer matrix. The films were evaluated with respect to assay, content uniformity, excipient interaction, and permeability across isolated rabbit sclera. The distribution of TA in the ocular tissues, post topical administration, was determined in New Zealand male albino rabbits as a function of dose, and was compared against TA-C. The assay of the 10% and 20% w/w film was in the range from 70–79% and 92–94% for the Soluplus® and PEO films, respectively, and content uniformity was in the range of 95–103% for both the films. The assay of the TA from Soluplus® films was less compared with the PEO films and showed an interaction with TA, as revealed by Differential Scanning Calorimetry (DSC). Hence, Soluplus® films were not selected for further studies. No interaction was observed between the drug and PEO polymer matrix. The enhancement of trans-scleral flux and permeability of TA was about 1.16 and 1.33-folds, respectively, from the 10% w/w PEO and 3.5 and 2.12-folds, respectively, from the 20% w/w PEO films, as compared with TA-C formulations. The in vivo studies demonstrate that significantly higher TA levels were observed in the anterior and posterior segments of the eye at the end of 6h with the PEO films. Therefore, the PEO based polymeric films were able to deliver TA into the back of the eye efficiently and for prolonged periods.

scholarly journals A Mini Review on Antidiabetic Properties of Fermented Foods

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1973 ◽  
Author(s):  
Bhagavathi Sivamaruthi ◽  
Periyanaina Kesika ◽  
Mani Prasanth ◽  
Chaiyavat Chaiyasut
Keyword(s):  
Functional Properties ◽  
Antioxidant Properties ◽  
Treatment Strategies ◽  
In Vivo Studies ◽  
Fermented Foods ◽  
Gastrointestinal Health ◽  
Randomized Controlled Clinical Trials ◽  
The Government

In general, fermented foods (FFs) are considered as functional foods. Since the awareness about the health benefits of FFs has increased, the consumption of FF also improved significantly in recent decades. Diabetes is one of the leading threats of the health span of an individual. The present manuscript details the general methods of the production of FFs, and the results of various studies (in vitro, in vivo, and clinical studies) on the antidiabetic properties of FFs. The fermentation method and the active microbes involved in the process play a crucial role in the functional properties of FFs. Several in vitro and in vivo studies have been reported on the health-promoting properties of FFs, such as anti-inflammation, anticancer, antioxidant properties, improved cognitive function and gastrointestinal health, and the reduced presence of metabolic disorders. The studies on the functional properties of FFs by randomized controlled clinical trials using human volunteers are very limited for several reasons, including ethical reasons, safety concerns, approval from the government, etc. Several scientific teams are working on the development of complementary and alternative medicines to improve the treatment strategies for hyperglycemia.

scholarly journals Anti-Hyperglycaemic Evaluation of Buddleia indica Leaves Using In Vitro, In Vivo and In Silico Studies and Its Correlation with the Major Phytoconstituents

Plants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2351
Author(s):  
Sameh S. Elhady ◽  
Fadia S. Youssef ◽  
Abdulrahman M. Alahdal ◽  
Diena M. Almasri ◽  
Mohamed L. Ashour
Keyword(s):  
Active Sites ◽  
Biological Activities ◽  
Serum Insulin ◽  
Ethyl Acetate Fraction ◽  
In Vivo Studies ◽  
Stress Markers ◽  
In Silico Studies ◽  
Streptozotocin Induced Diabetes

Buddleia indica Lam. is an ornamental evergreen shrub with few reports concerning its phytoconstituents and biological activities. Herein, the antihyperglycaemic activity of B. indica leaves methanol extract (BIT) was evaluated for the first time using in vitro and in vivo studies. Molecular modelling was performed for its major phytoconstituents that were further subjected to ADME/TOPAKT (absorption, distribution, metabolism, excretion and toxicity) prediction. BIT revealed considerable reduction in glucose concentration by 9.93% at 50 μg/mL using 3T3-L1 adipocyte culture. It displayed substantial inhibition versus α-glucosidase and α-amylase with IC50 205.2 and 385.06 μg/mL, respectively. In vivo antihyperglycaemic activity of BIT and the ethyl acetate fraction (BIE) was performed using streptozotocin-induced diabetes in rat model. BIT and BIE effectively ameliorate oxidative stress markers in addition to reducing serum blood glucose by 56.08 and 54.00%, respectively, and are associated with a substantial increase in serum insulin by 4.1 and 12.7%, respectively. This can be attributed to its richness with polyphenolic compounds comprising flavonoids, phenolic acids, phenyl propanoids and iridoids. Molecular docking showed that verbascoside and kaempferol displayed the highest fitting within human α-amylase (HA) and human α-glucosidase (HG) active sites, respectively. They showed reasonable pharmacokinetic, pharmacodynamic and toxicity properties, as revealed by ADME/TOPKAT study.

New Benzodioxole-based Pyrazoline Derivatives: Synthesis and Anticandidal, In silico ADME, Molecular Docking Studies

2018 ◽  
Vol 16 (1) ◽  
pp. 82-92 ◽  
Author(s):  
Ahmet Özdemir ◽  
Belgin Sever ◽  
Mehlika Dilek Altıntop
Keyword(s):  
In Silico ◽  
Fungal Infections ◽  
Computational Study ◽  
Docking Studies ◽  
In Vivo Studies ◽  
Heme Group ◽  
In Silico Studies ◽  
Nih 3T3

Background: Azoles are commonly used in the treatment and prevention of fungal infections. They suppress fungal growth by acting on the heme group of lanosterol 14α-demethylase enzyme (CYP51), thus blocking the biosynthesis of ergosterol. </P><P> Objectives: Due to the importance of pyrazolines in the field of antifungal drug design, we aimed to design and synthesize new pyrazoline-based anticandidal agents. Methods: New pyrazoline derivatives were synthesized via the reaction of 1-(chloroacetyl)-3-(2- thienyl)-5-(1,3-benzodioxol-5-yl)-2-pyrazoline with aryl thiols. These compounds were evaluated for their in vitro antifungal effects on Candida species. Docking studies were performed to predict the affinity of the most effective anticandidal agents to substrate binding site of CYP51. Furthermore, MTT assay was performed to determine the cytotoxic effects of the compounds on NIH/3T3 mouse embryonic fibroblast cell line. A computational study for the prediction of ADME properties of all compounds was also carried out. Results: Compounds 5, 8, 10 and 12 were found as the most potent anticandidal agents against Candida albicans and Candida glabrata in this series with the same MIC values of ketoconazole and they also exhibited low toxicity against NIH/3T3 cells. Docking results indicated that all these compounds showed good binding affinity into the active site of CYP51. In particular, chloro substituted compounds 8 and 12 bind to CYP51 through direct coordination with the heme group. According to in silico studies, compound 8 only violated one parameter of Lipinski’s rule of five, making it a potential orally bioavailable agent. Conclusion: Compound 8 was defined as a promising candidate for further in vitro and in vivo studies.

scholarly journals Autophagy and salivary gland cancer: A putative target for salivary gland tumors

Tumor Biology ◽  
2020 ◽  
Vol 42 (12) ◽  
pp. 101042832098056
Author(s):  
Evangelos Koustas ◽  
Panagiotis Sarantis ◽  
Margarita Theodorakidou ◽  
Michalis V Karamouzis ◽  
Stamatios Theocharis
Keyword(s):  
Salivary Gland ◽  
Current Knowledge ◽  
Treatment Options ◽  
Treatment Strategies ◽  
In Vivo Studies ◽  
Salivary Gland Cancer ◽  
Number Of Patients ◽  
Salivary Gland Carcinomas

Salivary gland carcinomas are a group of heterogeneous tumors of different histological subtypes, presenting relatively low incidence but the entire variable of types. Although novel treatment options for salivary gland carcinomas patients’ outcomes have improved, the treatment of this type of cancer is still not standardized. In addition, a significant number of patients, with a lack of optimal treatment strategies, have reduced survival. In the last two decades, a plethora of evidence pointed to the importance of autophagy, an essential catabolic process of cytoplasmatic component digestion, in cancer. In vitro and in vivo studies highlight the importance of autophagy in salivary gland carcinomas development as a tumor suppressor or promoter mechanism. Despite the potential of autophagy in salivary gland carcinomas development, no therapies are currently available that specifically focus on autophagy modulation in salivary gland carcinomas. In this review, we summarize current knowledge and clinical trials in regard to the interplay between autophagy and the development of salivary gland carcinomas. Autophagy manipulation may be a putative therapeutic strategy for salivary gland carcinomas patients.

scholarly journals Epigenetic roles of PIWI proteins and piRNAs in lung cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hadis Fathizadeh ◽  
Zatollah Asemi
Keyword(s):  
Lung Cancer ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
High Mobility ◽  
P Element ◽  
In Vivo Studies ◽  
Cancer Pathogenesis ◽  
Non Coding Rnas

AbstractLung cancer is one of very important malignancies which are related to high mobility and mortality in the world. Despite several efforts for improving diagnosis and treatment strategies of lung cancer, finding and developing new and effective therapeutic and diagnostic are needed. A variety of internal and external factors could be involved in lung cancer pathogenesis. Among internal factors, epigenetic mechanisms have been emerged as very important players in the lung cancer. Non-coding RNAs is known as one of epigenetic regulators which exert their effects on a sequence of cellular and molecular mechanisms. P-element induced wimpy testis (PIWI)-interacting RNAs (piRNAs or piR) is one of small non-coding RNAs that the deregulation of these molecules is associated with initiation and progression of different cancers such as lung cancer. Several activities are related to PIWI/piRNA pathway such as suppression of transposons and mobile genetic elements. In vitro and in vivo studies demonstrated the upregulation or downregulation of PIWI proteins and piRNAs could lead to the increasing of cell proliferation, apoptosis reduction and promoting tumor growth in the lung cancer. Hence, PIWI proteins and piRNA could be introduced as new diagnostic and therapeutic biomarkers in the lung cancer therapy. Herein, we have focused on PIWI proteins and piRNA functions and their impact on the progression of lung cancer.

An Insight into the Discovery of Potent Antifilarial Leads Against Lymphatic Filariasis

2020 ◽  
Vol 21 (7) ◽  
pp. 657-680
Author(s):  
Pone Kamdem Boniface ◽  
Ferreira Igne Elizabeth
Keyword(s):  
Lymphatic Filariasis ◽  
In Vivo Studies ◽  
Protein Targets ◽  
Scientific Databases ◽  
Naturally Occurring ◽  
In Silico Studies ◽  
Antifilarial Activity ◽  
Insight Into

Background and Objectives: Lymphatic filariasis is a neglected tropical disease caused by infection with filarial worms that are transmitted through mosquito bites. Globally, 120 million people are infected, with nearly 40 million people disfigured and disabled by complications such as severe swelling of the legs (elephantiasis) or scrotum (hydrocele). Current treatments (ivermectin, diethylcarbamazine) have limited effects on adult parasites and produce side effects; therefore, there is an urgent to search for new antifilarial agents. Numerous studies on the antifilarial activity of pure molecules have been reported accross the recent literature. The present study describes the current standings of potent antifilarial compounds against lymphatic filariasis. Methods: A literature search was conducted for naturally occurring and synthetic antifilarial compounds by referencing textbooks and scientific databases (SciFinder, PubMed, Science Direct, Wiley, ACS, SciELO, Google Scholar, and Springer, among others) from their inception until September 2019. Results: Numerous compounds have been reported to exhibit antifilarial acitivity in adult and microfilariae forms of the parasites responsible for lymphatic filariasis. In silico studies of active antifilarial compounds (ligands) showed molecular interactions over the protein targets (trehalose-6-phosphate phosphatase, thymidylate synthase, among others) of lymphatic filariasis, and supported the in vitro results. Conclusion: With reference to in vitro antifilarial studies, there is evidence that natural and synthetic products can serve as basic scaffolds for the development of antifilarial agents. The optimization of the most potent antifilarial compounds can be further performed, followed by their in vivo studies.

scholarly journals Pathogenesis of Keratinocyte Carcinomas and the Therapeutic Potential of Medicinal Plants and Phytochemicals

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1979
Author(s):  
Andrea Jess Josiah ◽  
Danielle Twilley ◽  
Sreejarani Kesavan Pillai ◽  
Suprakas Sinha Ray ◽  
Namrita Lall
Keyword(s):  
Cell Carcinoma ◽  
Therapeutic Potential ◽  
Treatment Strategies ◽  
In Vivo Studies ◽  
Contributing Factors ◽  
Alternative Approach ◽  
Transdermal Drug Delivery Systems ◽  
Novel Treatment Strategies

Keratinocyte carcinoma (KC) is a form of skin cancer that develops in keratinocytes, which are the predominant cells present in the epidermis layer of the skin. Keratinocyte carcinoma comprises two sub-types, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This review provides a holistic literature assessment of the origin, diagnosis methods, contributing factors, and current topical treatments of KC. Additionally, it explores the increase in KC cases that occurred globally over the past ten years. One of the principal concepts highlighted in this article is the adverse effects linked to conventional treatment methods of KC and how novel treatment strategies that combine phytochemistry and transdermal drug delivery systems offer an alternative approach for treatment. However, more in vitro and in vivo studies are required to fully assess the efficacy, mechanism of action, and safety profile of these phytochemical based transdermal chemotherapeutics.

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