Cit/CuS@Fe3O4-based and enzyme-responsive magnetic nanoparticles for tumor chemotherapy, photothermal, and photodynamic therapy

2016 ◽  
Vol 31 (7) ◽  
pp. 1010-1025 ◽  
Author(s):  
Xiali Zhu ◽  
Heqing Huang ◽  
Yingjie Zhang ◽  
Huijuan Zhang ◽  
Lin Hou ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Magnetic Nanoparticles ◽  
Drug Release ◽  
Degradation Mechanism ◽  
Great Promise ◽  
The Subject ◽  
The Individual ◽  
Mcf 7

Safe and efficient drug delivery in a controllable fashion, especially remote and repeatable switch of on-demand drug release, is the subject of widespread attention. A kind of magnetic nanoparticles (DOX-Cit/CuS@Fe3O4-NPs) simultaneously consisted of Cit/CuS@Fe3O4 and doxorubicin (DOX) was presented. The drug release from DOX-Cit/CuS@Fe3O4-NPs could be successfully triggered by the presence of gelatinase, showing great promise for tumor-targeted drug release through an enzymatic degradation mechanism. Compared with free DOX, DOX-Cit/CuS@Fe3O4-NPs could not only specially deliver Cit/CuS@Fe3O4 and DOX into MCF-7 cells, but also could greatly improve the quantity of ROS produced in MCF-7 cells under of 980 nm laser irradiation. DOX-Cit/CuS@Fe3O4-NPs also had highly selective accumulation at tumor tissue of S180 tumor-bearing mice, which were along with a magnet near the tumor site. Furthermore, when combined with NIR laser irridation, DOX-Cit/CuS@Fe3O4-NPs showed a higher antitumor efficacy than the individual therapies in vitro and in vivo. This study showed that DOX-Cit/CuS@Fe3O4-NPs could be used as a platform for tumor chemotherapy, photothermal and photodynamic therapy.

scholarly journals Synthesis and high antiproliferative activity of dehydroabietylamine pyridine derivatives in vitro and in vivo

2020 ◽  
Vol 477 (12) ◽  
pp. 2383-2399
Author(s):  
Fengyi Zhao ◽  
Wen Lu ◽  
Yuanyuan Xu ◽  
Li Xu ◽  
Jingjing Zhang ◽  
...  
Keyword(s):  
Umbilical Vein ◽  
A549 Cells ◽  
Great Promise ◽  
Pyridine Derivatives ◽  
Inhibition Rate ◽  
Low Toxicity ◽  
A549 Lung ◽  
Mcf 7

Several bioactive dehydroabietylamine Schiff-bases (L1−L4), amides (L5−L11) and complex CuL3(NO3)2, Cu(L5)3, Co(L6)2Cl2 had been synthesized successfully for developing more efficient but lower toxic antiproliferative compounds. Their antiproliferative activities to Hela (cervix), HepG2 (liver), MCF-7 (breast), A549 (lung) and HUVEC (umbilical vein, normal cell) were investigated in vitro. The toxicity of all compounds was less than dehydroabietylamine (L0). For HepG2 cells, L1, L2 and L3 had higher anti-HepG2 activity, especially L1 (0.52 µM) had highest anti-HepG2 activity but low toxicity. For MCF-7 cells, L1, L2, L3 and L4 had higher anti-MCF-7 activity, especially L3(0.49 µM) had highest anti-MCF-7 activity but low toxicity. For A549 cells, L2 and L3 had higher anti-A549 activity. Furthermore, L1 and L3 may be the great promise antiproliferative drugs with nontoxic side effects, due to the high anti-HepG2 and anti-MCF-7 inhibition rate in vivo, 65% and 61%, respectively. L1, L2 and L3 could induce apoptosis through intercalating into DNA.

scholarly journals Intracellular tracking of drug release from pH-sensitive polymeric nanoparticles via FRET for synergistic chemo-photodynamic therapy

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Chen Du ◽  
Yan Liang ◽  
Qingming Ma ◽  
Qianwen Sun ◽  
Jinghui Qi ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Drug Release ◽  
Real Time ◽  
Polymeric Nanoparticles ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Resonance Energy Transfer ◽  
Resonance Energy

Abstract Background Synergistic therapy of tumor is a promising way in curing cancer and in order to achieve effective tumor therapy with real-time drug release monitoring, dynamic cellular imaging and antitumor activity. Results In this work, a polymeric nanoparticle with Forster resonance energy transfer (FRET) effect and chemo-photodynamic properties was fabricated as the drug vehicle. An amphiphilic polymer of cyclo(RGDfCSH) (cRGD)-poly(ethylene glycol) (PEG)-Poly(l-histidine) (PH)-poly(ε-caprolactone) (PCL)-Protoporphyrin (Por)-acting as both a photosensitizer for photodynamic therapy (PDT) and absorption of acceptor in FRET was synthesized and self-assembled into polymeric nanoparticles with epirubicin (EPI)-acting as an antitumor drug for chemotherapy and fluorescence of donor in FRET. Spherical EPI-loaded nanoparticles with the average size of 150 ± 2.4 nm was procured with negatively charged surface, pH sensitivity and high drug loading content (14.9 ± 1.5%). The cellular uptake of EPI-loaded cRGD-PEG-PH-PCL-Por was monitored in real time by the FRET effect between EPI and cRGD-PEG-PH-PCL-Por. The polymeric nanoparticles combined PDT and chemotherapy showed significant anticancer activity both in vitro (IC50 = 0.47 μg/mL) and better therapeutic efficacy than that of free EPI in vivo. Conclusions This work provided a versatile strategy to fabricate nanoassemblies for intracellular tracking of drug release and synergistic chemo-photodynamic therapy.

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.  

A Novel Triazole Derivative Drug Presenting In Vitro and In Vivo Anticancer Properties

2018 ◽  
Vol 18 (17) ◽  
pp. 1483-1493
Author(s):  
Ricardo Imbroisi Filho ◽  
Daniel T.G. Gonzaga ◽  
Thainá M. Demaria ◽  
João G.B. Leandro ◽  
Dora C.S. Costa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Hepatic Function ◽  
Anticancer Properties ◽  
Mcf 7

Background: Cancer is a major cause of death worldwide, despite many different drugs available to treat the disease. This high mortality rate is largely due to the complexity of the disease, which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching for novel drugs that can target different and multiple aspects of cancer. Experimental: After a screening, we selected one novel molecule, out of ninety-four triazole derivatives, that strongly affects the viability and proliferation of the human breast cancer cell line MCF-7, with minimal effects on non-cancer cells. The drug, named DAN94, induced a dose-dependent decrease in MCF-7 cells viability, with an IC50 of 3.2 ± 0.2 µM. Additionally, DAN94 interfered with mitochondria metabolism promoting reactive oxygen species production, triggering apoptosis and arresting the cancer cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects are not observed when the drug was tested in the non-cancer cell line MCF10A. Using a mouse model with xenograft tumor implants, the drug preventing tumor growth presented no toxicity for the animal and without altering biochemical markers of hepatic function. Results and Conclusion: The novel drug DAN94 is selective for cancer cells, targeting the mitochondrial metabolism, which culminates in the cancer cell death. In the end, DAN94 has been shown to be a promising drug for controlling breast cancer with minimal undesirable effects.

Derivatives of Deoxypodophyllotoxin Induce Apoptosis Through Bcl-2/Bax Proteins Expression

2020 ◽  
Vol 20 ◽  
Author(s):  
Ya-Nan Li ◽  
Ni Ning ◽  
Lei Song ◽  
Yun Geng ◽  
Jun-Ting Fan ◽  
...  
Keyword(s):  
Annexin V ◽  
Mtt Method ◽  
Anthriscus Sylvestris ◽  
Anti Tumor Activity ◽  
Derivatives Of ◽  
Toxicity In Vitro ◽  
Ht 29 ◽  
Mcf 7

Background: Deoxypodophyllotoxin, isolated from theTraditional Chinese Medicine Anthriscus sylvestris, is well-known because of its significant antitumor activity with strong toxicity in vitro and in vivo. Objective: In this article, we synthesized a series of deoxypodophyllotoxin derivatives, and evaluated their antitumor effectiveness.Methods:The anti tumor activity of deoxypodophyllotoxin derivatives was investigated by the MTT method. Apoptosis percentage was measured by flow cytometer analysis using Annexin-V-FITC. Results: The derivatives revealed obvious cytotoxicity in the MTT assay by decreasing the number of late cancer cells. The decrease of Bcl-2/Bax could be observed in MCF-7, HepG2, HT-29 andMG-63 using Annexin V-FITC. The ratio of Bcl-2/Bax in the administration group was decreased, which was determined by the ELISA kit. Conclusion: The derivatives of deoxypodophyllotoxin could induce apoptosis in tumor cell lines by influencing Bcl-2/Bax.

Co-delivery of Doxorubicin and D-α-Tocopherol Polyethylene Glycol 1000 Succinate by Magnetic Nanoparticles

2018 ◽  
Vol 18 (8) ◽  
pp. 1138-1147 ◽  
Author(s):  
Esra Metin ◽  
Pelin Mutlu ◽  
Ufuk Gündüz
Keyword(s):  
Breast Cancer ◽  
Polyethylene Glycol ◽  
Magnetic Nanoparticles ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Drug Loading ◽  
Gravimetric Analysis ◽  
Polyethylene Glycol 1000 ◽  
Mcf 7

Background: Although conventional chemotherapy is the most common method for cancer treatment, it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given to body systemically, normal cells are also affected, just like cancer cells. However, in recent years, targeted drug delivery has been developed to overcome these drawbacks. Objective: The aim of this study was targeted co-delivery of doxorubicin (Dox) which is an anticancer agent and D-α-Tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS or simply TPGS) to breast cancer cells. For this purpose, Magnetic Nanoparticles (MNPs) were synthesized and coated with Oleic Acid (OA). Coated nanoparticles were encapsulated in Poly Lactic-co-Glycolic Acid (PLGA) and TPGS polymers and loaded with Dox. The Nanoparticles (NPs) were characterized by Fourier Transform Infrared (FTIR) spectroscopy, zetapotential analysis, Dynamic Light Scattering (DLS) analysis, Thermal Gravimetric Analysis (TGA) and Scanning Electron Microscope (SEM) analysis. Results: The results showed that NPs were spherical, superparamagnetic and in the desired range for use in drug targeting. The targetability of NPs was confirmed. Moreover, TPGS and Dox loading was shown by TGA and FTIR analyses. NPs were internalized by cells and the cytotoxic effect of drug loaded NPs on sensitive (MCF-7) and drug-resistant (MCF-7/Dox) cells were examined. It was seen that the presence of TPGS increased cytotoxicity significantly. TPGS also enhanced drug loading efficiency, release rate, cellular internalization. In MCF- 7/Dox cells, the drug resistance seems to be decreased when Dox is loaded onto TPGS containing NPs. Conclusion: This magnetic PLGA nanoparticle system is important for new generation targeted chemotherapy and could be used for breast cancer treatment after in vivo tests.

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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