scholarly journals Toxicity, Pharmacokinetics, And Antitumor Activity Study of a Novel Long-Acting Paclitaxel Nanodrug Delivery System Constructed On a Curcumin Derivative Carrier

2021 ◽  
Author(s):  
chao Pi ◽  
Mingtang Zeng ◽  
Jingwen Ma ◽  
Pu Guo ◽  
Hongping Shen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Delivery System ◽  
Average Particle Size ◽  
Average Particle ◽  
Cytotoxicity Test ◽  
Nanodrug Delivery ◽  
Cumulative Toxicity ◽  
Curcumin Derivative

Abstract Purpose/Background: Paclitaxel (PTX) has been widely used in the clinic to treat breast cancer. However, its poor water solubility and intolerable toxicity greatly reduce the efficacy and medication safety. In this paper, a curcumin derivative (CUD) synthesized by the research group was used as a carrier to prepare a new type of PTX nanodrug delivery system (CUD-PTX-LN), thereby improving the safety of PTX medication and enhancing the anti-tumor effect.Methods: CUD-PTX-LN was prepared by solid dispersion technology and the dialysis method was adopted to investigate the release behavior of CUD-PTX-LN in vitro. Meanwhile, the dynamic process of nanoparticles in vivo was analyzed by pharmacokinetic experiments. Hemolysis experiment, acute toxicity and cumulative toxicity were conducted in mice to evaluate the safety of CUD-PTX-LN. Subsequently, the anti-tumor activity of CUD-PTX-LN was investigated using in vitro and in vivo breast cancer cell models.Results: The average particle size, PDI, and Zeta potential of CUD-PTX-LN were 238.5 ± 4.79 nm, 0.225 ± 0.011 and -33.8 ± 1.26 mV, respectively. CUD-PTX-LN had an encapsulation efficiency (%EE) of 94.20 ± 0.49% and an achievable drug loading (%DL) of 10.98 ± 0.31%. This nanoparticle was stable for up to half a year when the lyophilized powder was stored at room temperature. Cytotoxicity test on MCF-7 cells demonstrated the stronger cytotoxic activity of nanoparticles in comparison to free PTX. CUD-PTX-LN significantly prolonged the half-life and retention time of PTX. The area under the curve (AUC) of CUD-PTX-LN was 14.72 mg/L × h, which was 6 times that of the free PTX group (2.38 mg/L × h). In anti-tumor experiments in vivo, CUD-PTX-LN possessed the advantages of improving the antitumor efficacy and reducing the toxic side effects of drugs. Importantly, CUD-PTX-LN is safer than free PTX in terms of assessing hemolytic, acute and cumulative toxicity.Conclusion: A novel PTX nanodrug delivery system constructed based on CUD as a carrier holds great potential in improving breast cancer treatment.

Enhanced oral bioavailability of nisoldipine-piperine-loaded poly-lactic-co-glycolic acid nanoparticles

2017 ◽  
Vol 6 (6) ◽  
pp. 517-526 ◽  
Author(s):  
Permender Rathee ◽  
Anjoo Kamboj ◽  
Shabir Sidhu
Keyword(s):  
Oral Bioavailability ◽  
Drug Loading ◽  
Average Particle Size ◽  
Entrapment Efficiency ◽  
Pharmacokinetic Interaction ◽  
Precipitation Method ◽  
Pharmacokinetic Studies ◽  
Average Particle

AbstractBackground:Piperine helps in the improvement of bioavailability through pharmacokinetic interaction by modulating metabolism when administered with other drugs. Nisoldipine is a substrate for cytochrome P4503A4 enzymes. The study was undertaken to assess the influence of piperine on the pharmacokinetics and pharmacodynamics of nisoldipine nanoparticles in rats.Methods:Optimization studies of nanoparticles were performed using Taguchi L9 orthogonal array, and the nanoparticles were formulated by the precipitation method. The influence of piperine and nanoparticles was evaluated by means of in vivo kinetic and dynamic studies by oral administration in rats.Results:The entrapment efficiency, drug loading, ζ potential, and average particle size of optimized nisoldipine-piperine nanoparticles was 89.77±1.06%, 13.6±0.56%, −26.5 mV, and 132±7.21 nm, respectively. The in vitro release in 0.1 n HCl and 6.8 pH phosphate buffer was 96.9±0.48% and 98.3±0.26%, respectively. Pharmacokinetic studies showed a 4.9-fold increase in oral bioavailability and a >28.376±1.32% reduction in systemic blood pressure by using nanoparticles as compared to control (nisoldipine suspension) in Wistar rats.Conclusion:The results revealed that piperine being an inhibitor of cytochrome P4503A4 enzymes enhanced the bioavailability of nisoldipine by 4.9-fold in nanoparticles.

200 Developing exosomes as a mediator for CRISPR/Cas-9 delivery

2019 ◽  
Vol 31 (1) ◽  
pp. 225
Author(s):  
N. Gupta ◽  
K. Polkoff ◽  
L. Qiao ◽  
K. Cheng ◽  
J. Piedrahita
Keyword(s):  
Delivery System ◽  
Average Particle Size ◽  
Cell Uptake ◽  
Proteinase K ◽  
Target Cells ◽  
Average Particle ◽  
Loading Efficiency ◽  
Fetal Fibroblasts ◽  
In Vivo Delivery

CRISPR/Cas systems present a powerful gene-editing tool with the potential for widespread therapeutic use; however, current methods of in vivo delivery such as adeno-associated viruses (AAV) may stimulate an immune response, creating the need for an alternative for delivery of CRISPR/Cas9. Exosomes are small vesicles that are released by cells and serve as a delivery system for RNA, proteins, and various molecules to other cells. The focus of this project was to use exosomes as a delivery system for Cas9, exploiting their high uptake by target cells and their ability to avoid the immune system in vivo. Porcine fetal fibroblasts (PFF) were grown to 80% confluency; after 48h, exosomes were isolated and concentrated from conditioned media by filtration with a 0.22-μm filter followed by 100-kDa molecular weight cutoff filter. Transmission electron microscopy, Western blotting for presence of CD81, and an uptake assay for exosomes stained with the lipophilic dye DiI (Invitrogen/Thermo Fisher Scientific, Waltham, MA, USA) were used to characterise isolated exosomes, and average particle size was evaluated by NanoSight (Salisbury, United Kingdom). After characterisation, exosomes were loaded with Cas9 (PNA Bio, Newbury Park, CA, USA) using sonication, incubation with saponin, or extrusion. For each method of loading, 1.0×1011 exosomes and 500ng of Cas9 were used. For sonication, exosomes and Cas9 were sonicated 4 times: 4s on/2s off, left on ice for 2min, and then repeated for 4 more cycles. Loaded exosomes were then incubated at 37°C for 20min. For incubation with saponin, 100μL of 0.6% saponin solution was made in PBS, mixed with exosomes and Cas9, and then incubated on a shaker at 800 rpm for 20min. For extrusion, exosomes and Cas9 were extruded (Avanti Polar Lipids, Alabaster, AL, USA) 10, 15, or 20 times through a 0.22-μm filter. To evaluate efficiency of Cas9 loading into exosomes, loaded exosome samples were split in half, with one-half receiving a proteinase K digest (100μg mL−1) to remove free Cas9 and the other receiving no treatment. Proteinase K-treated and untreated samples were then compared side by side on Western blot staining for Cas9. ImageJ software (National Institutes for Health, Bethesda, MD, USA) was used to quantify band intensity and loading efficiency. With optimal conditions, our preliminary results show loading efficiency for sonication and saponin to be 16.7 and 19.2%, respectively, whereas loading by extrusion was undetectable. For CRISPR/Cas targeting, transgenic PFF carrying one copy of H2B-GFP were used to test delivery of ribonucleotide protein complex (RNP). To verify efficiency of the guide (g)RNA targeting green fluorescent protein (GFP), cells were nucleofected with Cas9 and gRNA. The DNA was extracted, PCR amplified, and sequenced (Eton Bioscience, San Diego, CA, USA) and then evaluated for indels with TIDE, resulting in a 53.2% cleavage efficiency. Next, exosomes will be loaded with RNP to knockout GFP in H2B-GFP cells, and targeting efficiency will be evaluated by flow cytometry and TIDE. We hypothesise that based on loading efficiency and target cell uptake, exosomes will present a safe and efficient method for in vitro and in vivo delivery of Cas9. The financial support of the Comparative Medicine Institute is gratefully acknowledged.

A smart ATP-responsive chemotherapy drug-free delivery system using a DNA nanostructure for synergistic treatment of breast cancer in vitro and in vivo

2020 ◽  
Vol 28 (7-8) ◽  
pp. 852-859 ◽  
Author(s):  
Khalil Abnous ◽  
Noor Mohammad Danesh ◽  
Mohammad Ramezani ◽  
Mona Alibolandi ◽  
Amirhossein Bahreyni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Delivery System ◽  
Chemotherapy Drug ◽  
Dna Nanostructure ◽  
Drug Free

scholarly journals Erythrocyte Membrane-Coated Arsenic Trioxide-Loaded Sodium Alginate Nanoparticles for Tumor Therapy

Pharmaceutics ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 21 ◽  
Author(s):  
Yumei Lian ◽  
Xuerui Wang ◽  
Pengcheng Guo ◽  
Yichen Li ◽  
Faisal Raza ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Sodium Alginate ◽  
Primary Liver Cancer ◽  
Tumor Therapy ◽  
Average Particle Size ◽  
In Vivo Studies ◽  
Average Particle ◽  
Promising Alternative

Arsenic trioxide (ATO) has a significant effect on the treatment of acute promyelocytic leukemia (APL) and advanced primary liver cancer, but it still faces severe side effects. Considering these problems, red blood cell membrane-camouflaged ATO-loaded sodium alginate nanoparticles (RBCM-SA-ATO-NPs, RSANs) were developed to relieve the toxicity of ATO while maintaining its efficacy. ATO-loaded sodium alginate nanoparticles (SA-ATO-NPs, SANs) were prepared by the ion crosslinking method, and then RBCM was extruded onto the surface to obtain RSANs. The average particle size of RSANs was found to be 163.2 nm with a complete shell-core bilayer structure, and the average encapsulation efficiency was 14.31%. Compared with SANs, RAW 264.7 macrophages reduced the phagocytosis of RSANs by 51%, and the in vitro cumulative release rate of RSANs was 95% at 84 h, which revealed a prominent sustained release. Furthermore, it demonstrated that RSANs had lower cytotoxicity as compared to normal 293 cells and exhibited anti-tumor effects on both NB4 cells and 7721 cells. In vivo studies further showed that ATO could cause mild lesions of main organs while RSANs could reduce the toxicity and improve the anti-tumor effects. In brief, the developed RSANs system provides a promising alternative for ATO treatment safely and effectively.

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>

scholarly journals ETHYLCELLULOSE FLOATING MICROSPHERES OF ANTIDIABETIC AGENT: IN VITRO AND IN VIVO EVALUATION

2016 ◽  
Vol 9 (1) ◽  
pp. 44 ◽  
Author(s):  
Seema Kohli ◽  
Megha Sharma ◽  
Abhisek Pal
Keyword(s):  
Average Particle Size ◽  
Insulin Dependent Diabetes Mellitus ◽  
Treated Group ◽  
Antidiabetic Activity ◽  
Dependent Diabetes Mellitus ◽  
Average Particle ◽  
In Vivo Evaluation ◽  
Gastro Retentive

Objective: To develop and evaluate floating type gastro-retentive dosage form, appropriate for controlled release of repaglinide (RG) having a narrow therapeutic window.Methods: Repaglinide loaded microspheres (MS) using biological macromolecule ethylcellulose (EC) was prepared by a solvent diffusion-evaporation technique using polyvinyl alcohol (PVA) emulsifier. Compatibility of drug and polymer was studied by Fourier-transform infrared spectroscopy (FTIR). During formulation, various process optimisation parameters studied were stirring speed, the concentration of drug, polymer and emulsifier. Characterization and in vitro evaluation was performed. In vivo antidiabetic activity was performed on alloxan induced diabetic rats followed by histopathological screening.Results: The average particle size was in the range of 174-243 µm. Yield, entrapment and buoyancy of microspheres were 68.4­­-79.8, 58.6-73.1 and 71.8-84.1% respectively. 65.1% release of drug from optimised formulation was obtained which follows first-order kinetics (r2 = 0.989). Optimised formulation treated group shows significant (p<0.01) decrease in glucose level of blood as compared to pure drug treated group during the later hours of study with satisfactory results of histology.Conclusion: The investigation revealed the promising potential of gastro retentive microspheres for delivering RG for the treatment of non-insulin dependent diabetes mellitus (NIDDM).

Hepatocellular Carcinoma Targeting and Pharmacodynamics of Paclitaxel Nanoliposomes Modified by Glycyrrhetinic Acid and Ferric Tetroxide

2021 ◽  
Vol 21 ◽  
Author(s):  
Ling Zhao ◽  
Leyi Liang ◽  
Mimi Guo ◽  
Ming Li ◽  
Xuesong Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Delivery ◽  
Average Particle Size ◽  
In Vitro Release ◽  
Glycyrrhetinic Acid ◽  
Migration And Invasion ◽  
Average Particle ◽  
Hcc Cells

Aims: Research on developing targeted delivery of anticancer drugs for the treatment of hepatocellular carcinoma (HCC) is ongoing. This study aimed at synthesizing nanoliposomes modified by glycyrrhetinic acid (GA) and ferric tetroxide (Fe3O4) for targeted delivery of paclitaxel for selective and specific therapy of HCC. Objective: During this project, GA and Fe3O4 were used to jointly modify the active targeting and magnetic orientation of paclitaxel nanoliposomes for enhanced targeting of HCC to improve the efficacy, while reducing the systemic toxicity and side effects of the drug. Methods: In this study, liposomes were prepared to utilize a thin film dispersion method, in which the average particle size of GA/Fe3O4-PTX-LP was 148.9 ± 2.3 nm, and the average Zeta potential was -23.2 ± 3 mV. Based on the TEM characterization, GA/Fe3O4-PTX-LP is a closed particle with bilayer membranes. In vitro release assessments of the drug indicated that the release of GA/Fe3O4-PTX-LP was sustained. Results: In vitro cell tests have demonstrated that GA/Fe3O 4-PTX-LP can inhibit the proliferation, affect the morphology, migration and invasion, and interfere with the cycle of HCC cells. Uptake tests have confirmed that GA/Fe3O4-PTX-LP can promote the uptake of the drug in HCC cells. Conclusion: In vivo targeting experiments have shown that GA/Fe3O4-PTX-LP has a strong ability to target tumors. In vivo antitumor assessments have proven that GA/Fe3O4-PTX-LP can inhibit tumor growth without obvious toxicity. This project provides a promising nano-targeted drug delivery system for the treatment of HCC.

Thioaptamer-conjugated CD44-targeted delivery system for the treatment of breast cancer in vitro and in vivo

2015 ◽  
Vol 24 (4) ◽  
pp. 359-371 ◽  
Author(s):  
Wei Fan ◽  
Xiang Wang ◽  
Baoyue Ding ◽  
Haimin Cai ◽  
Xudong Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Delivery System ◽  
Targeted Delivery ◽  
Targeted Delivery System

scholarly journals Preparation and Characterization of Paclitaxel Palmitate Albumin Nanoparticles With High Loading Efficacy: an in Vitro and in Vivo Anti-tumor Study in Mouse Models

2020 ◽  
Author(s):  
Hang Chen ◽  
Sifan Huang ◽  
Heyi Wang ◽  
Xinmei Chen ◽  
Haiyan Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Drug Loading ◽  
The Body ◽  
Albumin Nanoparticles ◽  
Loading System

Abstract Background: Combination of the prodrug technique with an albumin nanodrug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives. Results: In this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the NabTM technology of paclitaxel palmitate (PTX-PA). Our experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin NPs (Nab-PTX-PA) remained in the tumor for a longer time post injection. Compared with saline and Abraxane® (nanoparticle albumin-bound (nab)-paclitaxel), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organsand more importantly it inhibited tumor cell proliferation more effectively as compared with commercial Abraxane®.Conclusions: This carrier strategy for small molecule drugs is based on naturally evolved interactions between LCFAs(Long Chain Fatty Acids) and HSA(human serum albumin), demonstrated here for PTX. Nab-PTX-PA shows higher maximum tolerated doses and increased efficacy in vivo in breast cancer models, as compared to Abraxane for FDA-approved clinical formulations. This novel injectable Nab-PTX-PA platform has great potential as an effective drug delivery system in the treatment of breast cancer.

Construction of long-circulation EpCAM targeted drug delivery system and its application in the diagnosis and treatment of breast cancer

2020 ◽  
pp. 088532822096513
Author(s):  
Chao Song ◽  
Chao Gao ◽  
Jing Zhao ◽  
Zhenxin Wang
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Targeted Drug Delivery ◽  
Drug Carrier ◽  
Average Particle Size ◽  
Average Particle ◽  
Tumor Focus ◽  
Targeted Drug

Docetaxel (DOX) is usually one of drugs used for breast cancer treatment. The key of targeted drug delivery therapy is to deliver effective drugs directly and safely to the tumor focus via an efficient targeting drug carrier with immunogenicity. In this study, Long-circulating targeted drug carrying microspheres (DOX-PEG-EpCAM-MNs) entrapping DOX were constructed. In addition, both cytotoxicity and magnetic resonance imaging (MRI) analyses were performed to establish a mouse model and further complete corresponding performance analysis.The results showed that the average particle size of DOX-PEG-EpCAM-MNs was 139.3 ± 1.6 nm. Morphological analysis proves that they are spherical and uniformly dispersed. The Corresponding entrapment rate and drug carrying capacity are 82.43% and 7.16% respectively. Additionally, MRI shows that they have the capability to track tumor cells within 5 days. This study established a safe and efficient breast cancer cells targeted long-circulating drug delivery system.

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