Encapsulation of Ellagic Acid in Di-Block Copolymeric Micelle for Non-Small Cell Lung Cancer Therapy

2021 ◽  
Vol 13 (1) ◽  
pp. 66-72
Author(s):  
Serag Eldin I. Elbehairi ◽  
Mohammad Y. Alfaifi ◽  
Ali A. Shati ◽  
Usama A. Fahmy ◽  
Bapi Gorain ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Ellagic Acid ◽  
Polymeric Micelles ◽  
A549 Cells ◽  
Entrapment Efficiency ◽  
Aqueous Solubility ◽  
Polymeric Micelle ◽  
Lung Adenocarcinoma Cell Line ◽  
Lung Cancer Therapy ◽  
Poly Ethylene

Ellagic acid (EA) is an anticancer agent as evidenced in numerous pre-clinical studies. The clinical application of EA is limited because of its poor aqueous solubility and bioavailability. The present study was designed to formulate polymeric micelles of the drug using poly(L-lactide-co-glycolide)-poly (ethylene glycol) (PLGA-PEG) di-block copolymer. The particle size and entrapment efficiency of EA by the polymeric micelle were found to be dependent on the concentration of polymer. Consequently, optimized micellar formulations with 82 ± 7.1 nm size and 45.32 ± 5.43% drug entrapment were further evaluated for cytotoxicity, cell cycle arrest, and apoptotic potential in the human lung adenocarcinoma cell line, A549. EA was toxic to A549 cells, and this cytotoxicity was significantly increased when EA was delivered using a micellar formulation. Flow cytometry analysis revealed a superior G1 phase arresting potential of the optimized EA-loaded PLGA-PEG micelles (PLGA-PEG-EA-F3), with a concomitant increased apoptotic potential. Further investigation of the mechanism of apoptosis showed a significant overexpression of caspase-3 in A549 cells when treated with PLGA-PEG-EA-F3 compared to free EA. Thus, it can be concluded that the PLGA-PEG polymeric micellar platform for EA could be a potential tool to treat lung cancer.

scholarly journals Synthesis, Characterization, and Evaluation of Radical Scavenging Ability of Ellagic Acid-Loaded Nanogels

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Gautam Behl ◽  
Monal Sharma ◽  
Saurabh Dahiya ◽  
Aruna Chhikara ◽  
Madhu Chopra
Keyword(s):  
Ellagic Acid ◽  
Encapsulation Efficiency ◽  
Drug Loading ◽  
Radical Scavenging ◽  
Aqueous Solubility ◽  
Loading Level ◽  
Human Cervical Cancer Cell ◽  
Poly Ethylene ◽  
Radical Scavenging Ability ◽  
Acid Loading

Ellagic acid (EA), a potential antioxidant phytochemical has low aqueous solubility and bioavailability. In this paper, encapsulation of ellagic acid has been carried out into the biodegradable disulfide crosslinked poly (ethylene glycol) PEO-based nanogels synthesized via AGET (activator generated electron transfer) ATRP (atom transfer radical polymerization), and their radical scavenging ability was evaluated. The encapsulation of the EA was carried out at two drug loading percentages, that is, 10 and 20 wt.% of the nanogels. 1,1-Diphenyl-2-picryldrazyl (DPPH) assay was utilized in order to assess the radical scavenging ability of the ellagic acid-loaded nanogels. A drug-loading level of about 2.5 wt.% was achieved with encapsulation efficiency of about 25% at 10 wt.% of the EA w.r.t nanogels, which was found to increase to about 4.7 wt.% with decreased encapsulation efficiency of 23.5% as EA content was increased to 20wt.% of the nanogels. Ellagic acid loading was found to be accompanied with increase in the size of the nanogels from144.6±39.52 nm for neat nanogels to217.8±105.5and633±160.1 nm at 2.5 and 4.7 wt.% drug loading level. The nanogels were found to be capable of scavenging radicals and biocompatible on human cervical cancer cell lines (HeLa cells) at appropriate concentrations.

scholarly journals Permeability of Ciprofloxacin-Loaded Polymeric Micelles Including Ginsenoside as P-glycoprotein Inhibitor through a Caco-2 Cells Monolayer as an Intestinal Absorption Model

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1904 ◽  
Author(s):  
Behzad Sharif Makhmal Zadeh ◽  
Golbarg Esfahani ◽  
Anayatollah Salimi
Keyword(s):  
Particle Size ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Aqueous Solubility ◽  
Polymeric Micelle ◽  
Maximum Effect ◽  
Drug Permeability ◽  
Intestinal Membrane ◽  
Full Factorial ◽  
Dose Dependent

The low oral bioavailability of ciprofloxacin is associated with two distinct challenges: its low aqueous solubility and efflux by p-glycoproteins (P-gp) in the intestinal membrane. Several studies were conducted in order to improve its solubility and permeability through the gastrointestinal membrane. In this study, in a full factorial design study, eight polymeric micelles were prepared and their characteristics, including particle size, loading and release rate were evaluated. Polymeric micelles demonstrated particle sizes below 190 nm and 27–88% loading efficiency. Drug release was affected by drug solubility, polymeric micelle erosion and swelling in simulated gastrointestinal fluids. An optimized polymeric micelle was prepared based on appropriate characteristics such as high drug loading and low particle size; and was used for a permeation study on Caco-2 cells. Optimized polymeric micelles with and without ginsenoside and ginsenoside alone enhanced drug permeability through Caco-2 cells significantly in the absorptive direction. The effect of ginsenoside was dose dependent and the maximum effect was seen in 0.23 mg/mL concentration. Results showed that P-gp may not be responsible for ciprofloxacin secretion into the gut. The main mechanism of ciprofloxacin transport through Caco-2 cells in both directions is active diffusion and P-gp has inhibitory effects on ciprofloxacin permeability in the absorptive direction that was blocked by ginsenoside and micelles without ginsenoside.

Recent advances in lung cancer therapy based on nanomaterials: a review

2021 ◽  
Vol 28 ◽  
Author(s):  
Leila Gholami ◽  
Jalil Rouhani Ivari ◽  
Niloofar Khandan Nasab ◽  
Reza Kazemi Oskuee ◽  
Thozhukat Sathyapalan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Cause Of Death ◽  
Polymeric Micelles ◽  
Industrialized Countries ◽  
Cancer Treatments ◽  
New Horizons ◽  
Recent Advances ◽  
Lung Cancer Therapy

: Lung cancer is one of the commonest cancers with a significant mortality rate for both genders, particularly in men. Lung cancer is recognized as one of the leading cause of death worldwide, which threatens the lives of over 1.6 million people every day.. Although cancer is the leading cause of death in industrialized countries, conventional anticancer medications are unlikely to increase patients' life expectancy and quality of life significantly. In recent years, there are significant advances in the development and application of nanotechnology in cancer treatment. The superiority of nanostructured approaches is that they act more selectively than traditional agents. This progress led to the development of a novel field of cancer treatment known as nanomedicine. Various formulations based on nanocarriers, including lipids, polymers, liposomes, nanoparticles and dendrimers have opened new horizons in lung cancer therapy. The application and expansion of nano-agents lead to an exciting and challenging research era in pharmaceutical science, especially for the delivery of emerging anti-cancer agents. The objective of this review is to discuss the recent advances in three types of nanoparticle formulations for lung cancer treatments modalities including liposomes, polymeric micelles, and dendrimers for efficient drug delivery. Afterward, we have summarized the promising clinical data on nanomaterials based therapeutic apperoches in ongoing clinical studies.

scholarly journals Polymeric micelle as a nanocarrier for delivery of therapeutic agents: A comprehensive review

2020 ◽  
Vol 10 (1-s) ◽  
pp. 191-195
Author(s):  
Roshani D. Agrawal ◽  
Amol A. Tatode ◽  
Nilesh R. Rarokar ◽  
Milind J. Umekar
Keyword(s):  
Drug Delivery ◽  
Ethylene Glycol ◽  
Polymeric Micelles ◽  
Molecular Geometry ◽  
Polymeric Micelle ◽  
Therapeutic Agents ◽  
Vinyl Pyrrolidone ◽  
Poly Ethylene Glycol ◽  
Isopropyl Acrylamide ◽  
Poly Ethylene

For selective and effective drug delivery of therapeutic agent nanocarriers are the most effective agents. Micelles are an aggregate of surfactant molecules that dispersed in a liquid colloid. Micelles have a variety of shapes such as spheres, rods, vesicles, tubules, and lamellae. The shape and size of a micelle are a function of the molecular geometry of its surfactant molecules and solution conditions such as surfactant concentration, temperature, pH, and ionic strength. Poly Ethylene Glycol (PEG) is the most commonly used hydrophilic segment of micelles for drug delivery. Besides PEG, other polymers including poly (N-vinyl pyrrolidone) (PVP) and poly (N-isopropyl acrylamide) (pNIPAM) have also been used as hydrophilic portion of micelles. In this review we all discus about the polymeric micelles (PMs) as a nanocarriers for delivery of therapeutic agents. Keywords: Polymeric Micelles, Colloids, Nanocarriers, Drug Delivery, Poly Ethylene Glycol(PEG)

scholarly journals Copolymeric Micelles Overcome the Oral Delivery Challenges of Amphotericin B

2020 ◽  
Vol 13 (6) ◽  
pp. 121
Author(s):  
Pataranapa Nimtrakul ◽  
Desmond B. Williams ◽  
Waree Tiyaboonchai ◽  
Clive A. Prestidge
Keyword(s):  
Amphotericin B ◽  
Oral Delivery ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Aqueous Solubility ◽  
Fold Increase ◽  
Free Drug ◽  
Absorption Studies

Classified as a Biopharmaceutical Classification System (BCS) class IV drug, amphotericin B (AmB) has low aqueous solubility and low permeability leading to low oral bioavailability. To improve these limitations, this study investigated the potential of AmB-loaded polymeric micelles (AmB-PM) to increase intestinal absorption. AmB-PM were prepared with polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol copolymer (Soluplus®) as a polymeric carrier and used a modified solvent diffusion and microfluidics (NanoAssemblr®) method. AmB-PM have a mean particle size of ~80 nm and are mono-disperse with a polydispersity index <0.2. The entrapment efficiency of AmB was up to 95% and achieved with a high drug loading up to ~20% (w/w) with a total amount of incorporated drug of 1.08 ± 0.01 mg/mL. Importantly, compared to free drug, AmB-PM protected AmB from degradation in an acidic (simulated gastric) environment. Viability studies in Caco-2 cells confirmed the safety/low toxicity of AmB-PM. In vitro cellular absorption studies confirmed that AmB-PM increased AmB uptake in Caco-2 cells 6-fold more than free AmB (i.e., 25% compared with 4% within 30 min). Furthermore, the permeability of AmB across Caco-2 monolayers was significantly faster (2-fold) and more pronounced for AmB-PM in comparison to free drug (3.5-fold increase). Thus, the developed AmB-PM show promise as a novel oral delivery system for AmB and justifies further investigation.

Diterpene 16-hydroxycleroda-3,13-dien-15,16-olide emerges non-canonical autophagic cell death in doxorubicin-resistant lung cancer

2020 ◽  
Author(s):  
Wei-Jun Chiu ◽  
Shian-Ren Lin ◽  
Chia-Jen Wu ◽  
Chun-Shu Lin ◽  
Prabhakar Busa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
A549 Cells ◽  
Mouse Lung ◽  
Small Cell Lung ◽  
Drug Discovery And Development ◽  
Investigation Methods ◽  
Anti Cancer ◽  
M Phase ◽  
Lung Cancer Therapy ◽  
Xenograft Mice

Abstract Background: The antitumor activity of HCD has been reported in numerous types of cancers. Moreover, the antitumor of HCD could also be applied in non-small-cell lung cancer (NSCLC) cells and further act on doxorubicin-resistant (Dox-R) of NSCLC cells. The underlying anti-cancer mechanism of HCD on Dox-R versus Dox-sensitive (Dox-S) of A549 cells was under this investigation. Methods: Cytotoxicity of HCD against two cell lines (Dox-S and Dox-R) were determined via MTT assay, flow cytometry, and Western blot; and further examination of its anti-cancer efficacy in A549-bearing xenograft mice via orthotopic intratrachea (IT) inoculation. Result: Regardless sensitive and resistant to Dox, HCD could arrest both Dox-S and Dox-R cells at G 2 /M phase without altering the sub-G 1 cycle along with increasing cleaved-PARP. HCD downregulated the mTOR/Akt/PI3K-p85 and PI 3 K-ClassIII/Beclin-1 and upregulated p62/LC3-I/II expressions, further confirmed the cell autophagy after HCD-induced. Morphological observations of the mouse lung sections illustrated that fewer cancer cells accumulated around the trachea while there were less neoplastic activities found in HCD orthotopic treatment mice without liver, kidney and spleen toxicity. Conclusion: HCD exhibited the chemotherapeutic potential for lung cancer in Dox-resistant cells, suggesting natural autophagic inducer HCD provides a promising clue of new drug discovery and development for lung cancer therapy.

scholarly journals Improved Pharmacokinetics of Icariin (ICA) within Formulation of PEG-PLLA/PDLA-PNIPAM Polymeric Micelles

Pharmaceutics ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 51 ◽  
Author(s):  
Lu-Ying Han ◽  
Yun-Long Wu ◽  
Chun-Yan Zhu ◽  
Cai-Sheng Wu ◽  
Chun-Rong Yang
Keyword(s):  
Lactic Acid ◽  
Polymeric Micelles ◽  
Polymeric Micelle ◽  
Pluronic F127 ◽  
In Vivo Experiments ◽  
Poly Ethylene ◽  
Metabolites Production ◽  
New Formulation

Icariin (ICA) is a major flavonoid that contains the active compound Epimedii Folium. However, ICA’s pharmacokinetic characteristics remain unsatisfactory due to its low bioavailability, and hence limited drugability. In order to improve its pharmacokinetics and achieve prolonged blood circulation time, a novel polymeric micelle, made of the self-assembled micelle between poly (ethylene glycol)-poly (L-lactic acid) (PEG-PLLA) and poly (D-lactic acid)-poly(N-isopropylacrylamide) (PDLA-PNIPAM), was designed to encapsulate ICA. Our experimental results showed that this polymeric micelle formulation of ICA exhibited uniform nano-size distribution and high stability within 48 h. The new formulation also allowed sustained ICA release in an in vitro drug release study. Furthermore, in vivo experiments revealed that ICA bioavailability in the PEG-PLLA/PDLA-PNIPAM polymeric micelle formulation was significantly higher compared to ICA alone, or ICA in the traditional Pluronic F127 micelle formulation. Finally, we show that metabolite analysis confirmed that ICA within the PEG-PLLA/PDLA-PNIPAM polymeric micelle formulation provided better drug protection, reduced drug metabolites production, and decreased undesired first-pass effects. Overall, these data show that ICA within PEG-PLLA/PDLA-PNIPAM polymeric micelle formulation exhibit advantages, in terms of improved physicochemical properties, sustained release of ICA in vitro, and improved bioavailability of ICA in vivo, which represent a feasible approach for improving the drugability of pharmaceutical small molecules with low bioavailability or poor stability.

Formulation, characterisation and In vitro cytotoxic effect of Lens culinarisMedikus seeds extract loaded chitosan microspheres

2021 ◽  
Vol 14 ◽  
Author(s):  
Kripi Vohra ◽  
Meenu Mehta ◽  
Vandana Garg ◽  
Kamal Dua ◽  
Harish Dureja
Keyword(s):  
Lung Cancer ◽  
Particle Size ◽  
Drug Release ◽  
Cytotoxic Effect ◽  
A549 Cells ◽  
Ethanolic Extract ◽  
Entrapment Efficiency ◽  
Reference Drug ◽  
Chitosan Microspheres

Objective: The aim of present study was to formulate chitosan microspheres loaded with ethanolic extract of Lens culinaris Medikus (L.culinaris) seeds (ME) and to explore its anticancer potential against lung cancer (A549) cell line. Methods: Central composite design was applied to prepare and optimise the chitosan microspheres. The prepared microspheres were evaluated for its physicochemical characterisation, in-vitro drug release and anti-cancer potential in-vitro. Results: L.culinaris loaded chitosan microspheres were prepared successfully with suitable particle size, entrapment efficiency and drug release. The developed ME were spherical shaped with the particle size of 2.08 µm. The drug entrapment efficiency and cumulative drug release was found 1.58±0.02% and 81.95±0.35% respectively. Differential Scanning Colorimetry studies revealed no interaction between drugs and polymers used. The cytotoxic effect of the optimised formulation revealed a significant response as compared to the ethanolic extract of L.culinaris seeds (IC50: 22.56 μg/ml vs. 63.58 μg/ml), which was comparable to that of reference drug, doxorubicin (22 µg/ml). These observations demonstrate that the optimised microspheres are effective against lung cancer(A549) cells. Conclusion: The significant cytotoxic response of the developed microspheres may be attributed due to its low particle size, high entrapment efficiency and prolonged drug release profile.

Self-Assembly Cascade Reaction Platform for CD44 Positive Lung Cancer Therapy

2021 ◽  
Vol 17 (12) ◽  
pp. 2374-2381
Author(s):  
Haitao Miao ◽  
Xiaoxiao Zhu ◽  
Fei Yuan ◽  
Qing Su ◽  
Pei Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Therapy ◽  
Self Assembly ◽  
Tumor Tissue ◽  
A549 Cells ◽  
Cascade Reaction ◽  
Peroxidase Mimic ◽  
Lung Cancers ◽  
Prussian Blue Nanoparticles ◽  
Lung Cancer Therapy

Lung cancer, as one of the most fatal cancers around the world, is responsible for the death of millions every year. Among various types of lung cancers, the ones overexpressing CD44 is usually associated higher cell proliferation with poorer prognosis. Therefore, finding a way to effectively treat CD44 positive lung cancer is urgently needed. Here in this study, negatively charged ultrasmall prussian blue nanoparticles (UPBNPs) was firstly synthesized and adsorbed to polyethyleneimine (PEI) together with glucose oxidase (Gox). Afterwards, the PEI was further complexed with hyaluronic acid (HA) to give a cascade reaction platform (HP/UPB-Gox) for CD44 positive lung cancer therapy. The HP/UPB-Gox with HA shell was able to positively target CD44 overexpressed A549 cells. Upon arriving at the tumor tissue, the Gox catalyzed the glucose of tumor to create H2O2, which further served as the substrate of UPBNPs, a peroxidase mimic, to finally give highly toxic hydroxyl radical (OH) for cancer therapy. Therefore, the cascade reaction formed between UPBNPs and Gox was expected to realize effective treatment on CD44 overexpressed lung cancer.

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