scholarly journals Preparation, Characterization, and Pharmacological Investigation of Withaferin-A Loaded Nanosponges for Cancer Therapy; In Vitro, In Vivo and Molecular Docking Studies

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6990
Author(s):  
Hamid Saeed Shah ◽  
Usman Nasrullah ◽  
Sumera Zaib ◽  
Faisal Usman ◽  
Ajmal Khan ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Tumour Volume ◽  
Docking Studies ◽  
Withaferin A ◽  
Target Cells ◽  
Scanning Calorimetry ◽  
Dapi Staining ◽  
Anticancer Efficacy

The rapidly growing global burden of cancer poses a major challenge to public health and demands a robust approach to access promising anticancer therapeutics. In parallel, nanotechnology approaches with various pharmacological properties offer efficacious clinical outcomes. The use of new artificial variants of nanosponges (NS) as a transporter of chemotherapeutic drugs to target cells has emerged as a very promising tool. Therefore, in this research, ethylcellulose (EC) NS were prepared using the ultrasonication assisted-emulsion solvent evaporation technique. Withaferin-A (WFA), an active ingredient in Withania somnifera, has been implanted into the nanospongic framework with enhanced anticancer properties. Inside the polymeric structure, WFA was efficiently entrapped (85 ± 11%). The drug (WFA) was found to be stable within polymeric nanosponges, as demonstrated by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies. The WFA-NS had a diameter of 117 ± 4 nm and zeta potential of −39.02 ± 5.71 mV with a polydispersity index (PDI) of 0.419 ± 0.073. In addition, scanning electron microscopy (SEM) revealed the porous surface texture of WFA-NS. In vitro anticancer activity (SRB assay) results showed that WFA–NS exhibited almost twice the anticancer efficacy against MCF-7 cells (IC50 = 1.57 ± 0.091 µM), as quantified by flow cytometry and comet tests. Moreover, fluorescence microscopy with DAPI staining and analysis of DNA fragmentation revealed apoptosis as a mechanism of cancer cell death. The anticancer activity of WFA-NS was further determined in vivo and results were compared to cisplatin. The anticancer activity of WFA-NS was further investigated in vivo, and the data were consistent to those obtained with cisplatin. At Day 10, WFA-NS (10 mg/kg) significantly reduced tumour volume to 72 ± 6%, which was comparable to cisplatin (10 mg/kg), which reduced tumour volume to 78 ± 8%. Finally, the outcomes of molecular modeling (in silico) also suggested that WFA established a stable connection with nanosponges, generating persistent hydrophobic contacts (polar and nonpolar) and helping with the attractive delayed-release features of the formulation. Collectively, all the findings support the use of WFA in nanosponges as a prototype for cancer treatment, and opened up new avenues for increasing the efficacy of natural product-derived medications.

scholarly journals Analysis Of Anticancer Activity And Its Molecular Interaction Mechanism Of Withanone, An Active Ingredient Of Withania Somnifera Using Molecular Docking

2021 ◽  
Vol 11 (6) ◽  
pp. 35-41
Author(s):  
Ben Raj ◽  
Madhan Shankar S. R.
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Withania Somnifera ◽  
Interaction Mechanism ◽  
B Cell Lymphoma ◽  
Withaferin A ◽  
Ligand Interaction ◽  
Anticancer Efficacy

Withania somnifera is an annual evergreen shrub from the Solanaceae family, commonly known as Indian ginseng or Ashwagandha. The plant is mainly found in Asia and Africa regions. In the traditional Indian medicinal system ayurveda, Withania somnifera is used as a rejuvenator and sold in many countries as a dietary supplement. Withanolides are the major phytochemical constituent group found in the Withania somnifera, among which withaferin A and withanone, are considered to be major withanolides, which believed to be involved in majority of biological activity of Withania somnifera. Various studies including both in vitro and in vivo have reported regarding the anticancer potential of Withania somnifera. Along with the anticancer activity of W.somnifera, the anticancer efficacy of one of its major ingredients Withaferin A is also studied previously. This study aimed to analyse the anticancer potential of another major Withanolide present in W. Somnifera, Withanone. The study used Molecular Docking method to find the molecular binding affinity of Withanone towards various cancer proteins. The four major cancer proteins were B-cell lymphoma- extra large (Bcl-xL), Cellular FLICE (c-FLIP), Glutathione Reductase (GR) and Glutathione S- Transferases (GST). The protein structure obtained from the protein data bank and the structure of the molecule obtained from pubchem were modified and prepared for Docking studies with the help of MGL Tools. The protein ligand interaction study was conducted using the software, Autodock vina. The already known anticancer standard, 5-FluoroUracil is used as standard for comparison. Output obtained from the study is visualised using molecular visualiser tool, Pymol. Like the Withaferin A, Withanone also exhibited promising anticancer activity while studied using molecular docking methods.

scholarly journals pH-responsive delivery vehicle based on RGD-modified polydopamine-paclitaxel-loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nanoparticles for targeted therapy in hepatocellular carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mingfang Wu ◽  
Chen Zhong ◽  
Qian Zhang ◽  
Lu Wang ◽  
Lingling Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Scanning Calorimetry ◽  
Anticancer Efficacy ◽  
Coated Nanoparticles ◽  
Transmission Electron ◽  
Sensitive Coating ◽  
Arginine Glycine Aspartic Acid ◽  
The Michael Addition

AbstractA limitation of current anticancer nanocarriers is the contradiction between multiple functions and favorable biocompatibility. Thus, we aimed to develop a compatible drug delivery system loaded with paclitaxel (PTX) for hepatocellular carcinoma (HCC) therapy. A basic backbone, PTX-loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) PHBV nanoparticle (PHBV-PTX-NPs), was prepared by emulsion solvent evaporation. As a gatekeeper, the pH-sensitive coating was formed by self-polymerization of dopamine (PDA). The HCC-targeted arginine-glycine-aspartic acid (RGD)-peptide and PDA-coated nanoparticles (NPs) were combined through the Michael addition. Subsequently, the physicochemical properties of RGD-PDA-PHBV-PTX-NPs were characterized by dynamic light scattering-autosizer, transmission electron microscope, fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetry and X-ray spectroscopy. As expected, the RGD-PDA-PHBV-PTX-NPs showed robust anticancer efficacy in a xenograft mouse model. More importantly, they exhibited lower toxicity than PTX to normal hepatocytes and mouse in vitro and in vivo, respectively. Taken together, these results indicate that the RGD-PDA-PHBV-PTX-NPs are potentially beneficial for easing conflict between multifunction and biocompatible characters of nanocarriers.

scholarly journals 6-SHOGAOL RICH GINGER OLEORESIN LOADED MIXED MICELLES ENHANCES IN VITRO CYTOTOXICITY ON MCF-7 CELLS AND IN VIVO ANTICANCER ACTIVITY AGAINST DAL CELLS

2018 ◽  
Vol 10 (1) ◽  
pp. 160 ◽  
Author(s):  
Kiran Kemkar ◽  
Sathiyanarayanan L. ◽  
Arulmozhi Sathiyanarayanan ◽  
Kakasaheb Mahadik
Keyword(s):  
Anticancer Activity ◽  
Mixed Micelles ◽  
In Vitro Release ◽  
In Vitro Cytotoxicity ◽  
Synergistic Activity ◽  
Scanning Calorimetry ◽  
Soya Lecithin ◽  
Assembly Method

Objective: Ginger oleoresin (GO) plays an important role on the attenuation of complications associated to the cancer which is attributed to 6-shogaol (6-SGL). The major challenge in using 6-SGL for therapeutic applications is its poor aqueous solubility, low stability in GI and low bioavailability. Considering the potent anticancer nature of 6-SGL and its synergistic activity with other constituents in GO, there is a need to develop a suitable drug delivery system.Methods: Thus in the present study, 6-SGL rich GO (6-SRGO) was incorporated into mixed micelles using phospholipid (Soya Lecithin) as a carrier. The prepared 6-SRGO loaded mixed micelles (6-SRGO-LMM) were characterized physically and chemically using Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and further evaluated for stability study, in vitro release study, in vitro cytotoxicity study and in vivo anticancer activity in comparison with 6-SRGO.Results: The composition such as, drug content (86.27±1.56), encapsulation efficiency (81.55±1.05) and particle size (356.11±4.07) were optimized using 32 factorial design. FTIR and DSC study confirm that the 6-SGL from 6-SRGO was entrapped in the core of phospholipid by self-assembly method to form mixed micelles. The 6-SRGO-LMM exhibited significant in vitro (GI50-23.2 μg/ml) and in vivo anticancer activity in comparison with 6-SRGO.Conclusion: We have developed and investigated mixed micelles composed of phospholipids (soya lecithin S80) and SCH as an effective nanocarrier for the delivery of a natural lipophilic anticancer bioactive 6-SGL from 6-SRGO.

ANTICANCER ACTIVITY OF DOXORUBICIN CONJUGATES WITH DENDRITIC POLYMERS OF SECOND GENERATION AND VECTOR PROTEIN IN MODEL SYSTEMS IN VITRO AND IN VIVO

2018 ◽  
Vol 64 (1) ◽  
pp. 131-137
Author(s):  
Irina Zamulaeva ◽  
Yevgeniy Severin ◽  
Irina Kondrasheva ◽  
Olga Zhunina ◽  
Sergey Makarenko ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Second Generation ◽  
Model Systems ◽  
Target Cells ◽  
Dendritic Polymers ◽  
Normal Tissues ◽  
P Glycoprotein ◽  
Mcf 7

Anticancer activity of doxorubicin (Dox), its conjugates with the second generation dendritic polymer (G2-Dox) and vector protein (recombinant third domain of alpha-fetoprotein - 3D-G2-Dox were studied in vitro and in vivo within the framework of the development of selective transport system of anticancer drugs to the target cells. The objects of the study were MCF-7 and MCF-7/MDR1 breast cancer cells, differing in chemosensitivity as well as mouse melanoma line B16. Anticancer activity of G2-Dox and 3D-G2-Dox was demonstrated in vivo (for B16 melanoma) and in vitro (for chemoresistant MCF-7/MDR1 cells, expressing P-glycoprotein). The effectiveness of anticancer action of G2-Dox and 3D-G2-Dox did not differ from that for free Dox. However for chemosensitive line MCF-7 free Dox proved to be more effective drug. It is important that the conjugates, and particularly 3D-G2-Dox, accumulated much weaker than the free Dox in normal cells isolated from bone marrow, spleen and liver of mice. The findings suggest that the main benefit from the possible use of such conjugates can be associated with reduced toxic effect of Dox on normal tissues and organs.

Long-Circulating, Temperature-Sensitive and EGFR-Targeted Liposomes for Drugs Delivery

2007 ◽  
Vol 342-343 ◽  
pp. 537-540 ◽  
Author(s):  
Sun Kyung Lim ◽  
Heon Joo Park ◽  
Eun Kyung Choi ◽  
Jin Seok Kim
Keyword(s):  
Growth Factor Receptor ◽  
Carcinoma Cells ◽  
Molar Ratio ◽  
Target Cells ◽  
Temperature Sensitive ◽  
Scanning Calorimetry ◽  
Epidermal Growth ◽  
Vitro Development

Effectiveness of epidermal growth factor receptor(EGFR)-targeted, long circulating and temperature-sensitive liposomes(TSLs) is described using sterically stabilized gemcitabine-loaded liposomes in vitro. Development of long-circulating formulation of TSLs with the EGFR antibody attached was designed to expect an increase in binding and drug delivery efficiency to the target cells such as non-small cell lung cancer cells(A549) and human pancreatic carcinoma cells(PANC- 1). New TSLs were prepared using DPPC:DMPC:DSPC(4:1:1 molar ratio) by the REV method. Differential scanning calorimetry of TSLs showed the phase-transition around 402. Release of a self-quenching fluorescent probe, calcein, from TSLs was studied for evaluation of temperaturesensitivity. Anti-proliferation effect of gemcitabine-loaded TSLs and antibody-conjugated TSLs in A549 and PANC-1 were higher than free drug. We conclude that sterically stabilized immunoliposomes exhibited good stability, ability to recognize target cells, and higher potency. Further studies, including in vivo animal study, are under investigation.

scholarly journals Mild Hyperthermia Responsive Liposomes for Enhanced In Vitro and In Vivo Anticancer Efficacy of Doxorubicin against Hepatocellular Carcinoma

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1310
Author(s):  
Muhammad Abdur Rahim ◽  
Asadullah Madni ◽  
Nayab Tahir ◽  
Nasrullah Jan ◽  
Hassan Shah ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Colloidal Stability ◽  
Drug Loading ◽  
In Vitro Cytotoxicity ◽  
Fickian Diffusion ◽  
Scanning Calorimetry ◽  
Mild Hyperthermia ◽  
Anticancer Efficacy

The current study is aimed to fabricate doxorubicin (Dox) loaded mild temperature responsive liposomes (MTLs) by thin film hydration technique for enhanced in vitro and in vivo anticancer efficacy against hepatocellular carcinoma. The aforementioned Dox loaded MTLs were developed and optimized with extrusion and drug loading techniques. The optimized MTLs were in optimum size range (118.20 ± 2.81–187.13 ± 4.15 nm), colloidal stability (−13.27 ± 0.04 to −32.34 ± 0.15 mV), and enhanced entrapment of Dox (28.71 ± 2.01–79.24 ± 2.16). Furthermore, the optimized formulation (MTL1-E(AL)) embodied improved physicochemical stability deducted by Fourier transform infra-red (FTIR) spectroscopy and mild hyperthermia-based phase transition demonstrated from differential scanning calorimetry (DSC). An in vitro drug release study revealed mild hyperthermia assisted rapid in vitro Dox release from MTLs-E(AL) (T100% ≈ 1 h) by Korsmeyer–Peppas model based Fickian diffusion (n < 0.45). Likewise, an in vitro cytotoxicity study and lower IC50 values also symbolized mild hyperthermia (40.2 °C) based quick and improved cytotoxicity of MTL1-E(AL) in HepG2 and MCF-7 cells than Dox. The fluorescence microscopy also represented enhanced cellular internalization of MTL1-E(AL) at mild hyperthermia compared to the normothermia (37.2 °C). In addition, an in vivo animal study portrayed the safety, improved anticancer efficacy and healing of hepatocellular carcinoma (HCC) through MTL1-E(AL). In brief, the Dox loaded MTLs could be utilized as safe and effective therapeutic strategy against HCC.

Vitamin D as potential therapeutic anticancer agent

2018 ◽  
pp. 1-3
Keyword(s):  
Vitamin D ◽  
Anticancer Activity ◽  
Anticancer Agent ◽  
Antitumor Agents ◽  
Metastatic Potential ◽  
Anticancer Properties ◽  
Chemotherapy Agents

The role of vitamin D is implicated in carcinogenesis through numerous biological processes like induction of apoptosis, modulation of immune system inhibition of inflammation and cell proliferation and promotion of cell differentiation. Its use as additional adjuvant drug with cancer treatment may be novel combination for improved outcome of different cancers. Numerous preclinical, epidemiological and clinical studies support the role of vitamin D as an anticancer agent. Anticancer properties of vitamin D have been studied widely (both in vivo and in vitro) among various cancers and found to have promising results. There are considerable data that indicate synergistic potential of calcitriol and antitumor agents. Possible mechanisms for modulatory anticancer activity of vitamin D include its antiproliferative, prodifferentiating, and anti-angiogenic and apoptic properties. Calcitriol reduces invasiveness and metastatic potential of many cancer cells by inhibiting angiogenesis and regulating expression of the key molecules involved in invasion and metastasis. Anticancer activity of vitamin D is synergistic or additive with the antineoplastic actions of several drugs including cytotoxic chemotherapy agents like paclitaxel, docetaxel, platinum base compounds and mitoxantrone. Benefits of addition of vitamin D should be weighed against the risk of its toxicity.

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

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.

Mannose Conjugated Starch Nanoparticles for Preferential Targeting of Liver Cancer

2020 ◽  
Vol 17 ◽  
Author(s):  
Akhlesh Kumar Jain ◽  
Hitesh Sahu ◽  
Keerti Mishra ◽  
Suresh Thareja
Keyword(s):  
Side Effects ◽  
Liver Cancer ◽  
Entrapment Efficiency ◽  
Xrd Analysis ◽  
In Vitro Cytotoxicity ◽  
Physical Interaction ◽  
Scanning Calorimetry ◽  
Starch Nanoparticles

Aim: To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for site specific delivery. Background: Liver cancer is the third leading cause of death in world and fifth most often diagnosed cancer is the major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of drug in normal tissues. Objective: To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for effective treatment of liver cancer. Materials and methods: 5-FU loaded JFSSNPs were prepared and optimized formulation had higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. Potential of NPs were studied using in vitro cytotoxicity assay, in vivo kinetic studies and bio-distribution studies. Result and discussion: 5-Fluorouracil loaded NPs had particle size between 336 to 802nm with drug entrapment efficiency was between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of drug in amorphous form. DSC study suggests there was no physical interaction between 5- FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assist selective accumulation of 5-FU in the liver (vs other organs spleen, kidney, lungs and heart) compared to unconjugated one and plain drug. Conclusion: In vivo, bio-distribution and plasma profile studies resulted in significantly higher concentration of 5- Fluorouracil liver suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.

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