scholarly journals Matrix metalloproteinase 2/9-triggered-release micelles for inhaled drug delivery to treat lung cancer: preparation and in vitro/in vivo studies

2018 ◽  
Vol Volume 13 ◽  
pp. 4641-4659 ◽  
Author(s):  
Xiaofei Wang ◽  
Qinyue Chen ◽  
Xiaoyan Zhang ◽  
Xiaoqing Ren ◽  
Xiulei Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Matrix Metalloproteinase ◽  
In Vivo Studies ◽  
Matrix Metalloproteinase 2 ◽  
Triggered Release ◽  
Inhaled Drug Delivery

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.

Self-assembled drug delivery systems. Part 6: In vitro/in vivo studies of anticancer N-octadecanoyl gemcitabine nanoassemblies

2012 ◽  
Vol 430 (1-2) ◽  
pp. 276-281 ◽  
Author(s):  
Yiguang Jin ◽  
Yanju Lian ◽  
Lina Du ◽  
Shuangmiao Wang ◽  
Chang Su ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
In Vivo Studies ◽  
Self Assembled

Novel Self-Micro Emulsifying Drug Delivery System for safe intra muscular delivery with improved pharmacodynamics and pharmacokinetics

2021 ◽  
Vol 18 ◽  
Author(s):  
Subheet Kumar Jain ◽  
Neha Panchal ◽  
Amrinder Singh ◽  
Shubham Thakur ◽  
Navid Reza Shahtaghi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Inflammatory Diseases ◽  
Diclofenac Sodium ◽  
Physical Stability ◽  
In Vivo Studies ◽  
High Concentration

Background: Diclofenac sodium (DS) injection is widely used in the management of acute or chronic pain and inflammatory diseases. It incorporates 20 % w/v Transcutol-P as a solubilizer to make the stable injectable formulation. However, the use of Transcutol-P in high concentration leads to adverse effects such as severe nephrotoxicity, etc. Some advancements resulted in the formulation of an aqueous based injectable but that too used benzyl alcohol reported to be toxic for human use. Objective: To develop an injectable self-micro emulsifying drug delivery system (SMEDDS) as a novel carrier of DS for prompt release with better safety and efficacy. Methods: A solubility study was performed with different surfactants and co-surfactants. The conventional stirring method was employed for the formulation of SMEDDS. Detailed in vitro characterization was done for different quality control parameters. In vivo studies were performed using Wistar rats for pharmacokinetic evaluation, toxicological analysis, and analgesic activity. Results: The optimized formulation exhibited good physical stability, ideal globule size (156±0.4 nm), quick release, better therapeutics, and safety, increase in LD50 (221.9 mg/kg) to that of the commercial counterpart (109.9 mg/kg). Further, pre-treatment with optimized formulation reduced the carrageenan-induced rat paw oedema by 88±1.2 % after 4 h, compared to 77±1.6 % inhibition with commercial DS formulation. Moreover, optimized formulation significantly (p<0.05) inhibited the pain sensation in the acetic-acid induced writhing test in mice compared to its commercial equivalent with a better pharmacokinetic profile. Conclusion: The above findings confirmed that liquid SMEDDS could be a successful carrier for the safe and effective delivery of DS

Polymeric/Inorganic Multifunctional Nanoparticles for Simultaneous Drug Delivery and Visualization

2010 ◽  
Vol 1257 ◽  
Author(s):  
Andrea Fornara ◽  
Alberto Recalenda ◽  
Jian Qin ◽  
Abhilash Sugunan ◽  
Fei Ye ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Fluorescence Microscopy ◽  
Contrast Agents ◽  
Gold Nanorods ◽  
In Vitro Cytotoxicity ◽  
In Vivo Studies ◽  
Multifunctional Nanoparticles ◽  
Cytotoxicity Studies

AbstractNanoparticles consisting of different biocompatible materials are attracting a lot of interest in the biomedical area as useful tools for drug delivery, photo-therapy and contrast enhancement agents in MRI, fluorescence and confocal microscopy. This work mainly focuses on the synthesis of polymeric/inorganic multifunctional nanoparticles (PIMN) based on biocompatible di-block copolymer poly(L,L-lactide-co-ethylene glycol) (PLLA-PEG) via an emulsion-evaporation method. Besides containing a hydrophobic drug (Indomethacin), these polymeric nanoparticles incorporate different visualization agents such as superparamagnetic iron oxide nanoparticles (SPION) and fluorescent Quantum Dots (QDs) that are used as contrast agents for Magnetic Resonance Imaging (MRI) and fluorescence microscopy together. Gold Nanorods are also incorporated in such nanostructures to allow simultaneous visualization and photodynamic therapy. MRI studies are performed with different loading of SPION into PIMN, showing an enhancement in T2 contrast superior to commercial contrast agents. Core-shell QDs absorption and emission spectra are recorded before and after their loading into PIMN. With these polymeric/inorganic multifunctional nanoparticles, both MRI visualization and confocal fluorescence microscopy studies can be performed. Gold nanorods are also synthesized and incorporated into PIMN without changing their longitudinal absorption peak usable for lased excitation and phototherapy. In-vitro cytotoxicity studies have also been performed to confirm the low cytotoxicity of PIMN for further in-vivo studies.

scholarly journals Lidocaine Alleviates Sepsis-Induced Acute Lung Injury in Mice by Suppressing Tissue Factor and Matrix Metalloproteinase-2/9

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Binbin Zheng ◽  
Hongbo Yang ◽  
Jianan Zhang ◽  
Xueli Wang ◽  
Hao Sun ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Matrix Metalloproteinase ◽  
Gelatin Zymography ◽  
Neutrophil Infiltration ◽  
Negative Regulator ◽  
Matrix Metalloproteinase 2 ◽  
Cytokine Signaling

Acute lung injury (ALI) is one of the fatal symptoms of sepsis. However, there were no effective clinical treatments. TF accumulation-induced fibrin deposit formations and coagulation abnormalities in pulmonary vessels contribute to the lethality of ALI. Suppressor of cytokine signaling 3 (SOCS3) acts as an endogenous negative regulator of the TLR4/TF pathway. We hypothesized that inducing SOCS3 expression using lidocaine to suppress the TLR4/TF pathway may alleviate ALI. Hematoxylin and eosin (H&E), B-mode ultrasound, and flow cytometry were used to measure the pathological damage of mice. Gelatin zymography was used to measure matrix metalloproteinase-2/9 (MMP-2/9) activities. Western blot was used to assay the expression of protein levels. Here, we show that lidocaine could increase the survival rate of ALI mice and ameliorate the lung injury of ALI mice including reducing the edema, neutrophil infiltration, and pulmonary thrombosis formation and increasing blood flow velocity. Moreover, in vitro and in vivo, lidocaine could increase the expression of p-AMPK and SOCS3 and subsequently decrease the expression of p-ASK1, p-p38, TF, and the activity of MMP-2/9. Taken together, our study demonstrated that lidocaine could inhibit the TLR4/ASK1/TF pathway to alleviate ALI via activating AMPK-SOCS3 axis.

scholarly journals STRUCTURE-BASED MULTITARGETED MOLECULAR DOCKING ANALYSIS OF PYRAZOLE-CONDENSED HETEROCYCLICS AGAINST LUNG CANCER

2021 ◽  
pp. 157-169
Author(s):  
JAINEY P. JAMES ◽  
AISWARYA T. C. ◽  
SNEH PRIYA ◽  
DIVYA JYOTHI ◽  
SHESHAGIRI R. DIXIT
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Binding Mode ◽  
Pharmacophore Modeling ◽  
In Vivo Studies ◽  
Spectral Studies ◽  
Pyrazole Derivatives ◽  
Anticancer Activities

Objective: The significant drawbacks of chemotherapy are that it destroys healthy cells, resulting in adverse effects. Hence, there is a need to adopt new techniques to develop cancer-specific chemicals that target the molecular pathways in a non-toxic fashion. This study aims to screen pyrazole-condensed heterocyclics for their anticancer activities and analyse their enzyme inhibitory potentials EGFR, ALK, VEGFR and TNKS receptors. Methods: The structures of the compounds were confirmed by IR, NMR and Mass spectral studies. The in silico techniques applied in this study were molecular docking and pharmacophore modeling to analyse the protein-ligand interactions, as they have a significant role in drug discovery. Drug-likeness properties were assessed by the Lipinski rule of five and ADMET properties. Anticancer activity was performed by in vitro MTT assay on lung cancer cell lines. Results: The results confirm that all the synthesised pyrazole derivatives interacted well with the selected targets showing docking scores above-5 kcal/mol. Pyrazole 2e interacted well with all the four lung cancer targets with its stable binding mode and was found to be potent as per the in vitro reports, followed by compounds 3d and 2d. Pharmacophore modeling exposed the responsible features responsible for the anticancer action. ADMET properties reported that all the compounds were found to have properties within the standard limit. The activity spectra of the pyrazoles predicted that pyrazolopyridines (2a-2e) are more effective against specific receptors such as EGFR, ALK and Tankyrase. Conclusion: Thus, this study suggests that the synthesised pyrazole derivatives can be further investigated to validate their enzyme inhibitory potentials by in vivo studies.

Redox Sensitive Polysaccharide Based Nanoparticles for Improved Cancer Treatment: A Comprehensive Review

2018 ◽  
Vol 24 (28) ◽  
pp. 3303-3319 ◽  
Author(s):  
Erfaneh Ghassami ◽  
Jaleh Varshosaz ◽  
Somayeh Taymouri
Keyword(s):  
Drug Delivery ◽  
Cancer Treatment ◽  
Drug Delivery Systems ◽  
Chemical Properties ◽  
Delivery Systems ◽  
Exchange Reactions ◽  
Triggered Release ◽  
Redox Responsive

Background: Among the numerous bio-responsive polymeric drug delivery systems developed recently, redox-triggered release of molecular payloads have gained great deal of attention, especially in the field of anticancer drug delivery. In most cases, these systems rely on disulfide bonds located either in the matrix crosslinks, or in auxiliary chains to achieve stimuli-responsive drug release. These bonds keep their stability in extracellular environments, yet, rapidly break by thiol–disulfide exchange reactions in the cytosol, due to the presence of greater levels of glutathione. Polysaccharides are macromolecules with low cost, natural abundance, biocompatibility, biodegradability, appropriate physical and chemical properties, and presence of numerous functional groups which facilitate chemical or physical cross-linking. Methods: With regards to the remarkable advantages of polysaccharides, in the current study, various polysaccharide-based redox-responsive drug delivery systems are reviewed. In most cases the in vitro/in vivo effects of the developed system were also evaluated. Results: Considering the hypoxic and reducing nature of the tumor microenvironment, with several folds higher glutathione levels than the systemic tissues, redox-sensitive polymeric systems could be implemented for tumorspecific drug delivery and the results of the previous researches in this field indicated satisfactory achievements. Conclusion: According to the reviewed papers, the efficiency of diverse redox-responsive polysaccharide-based nanoparticles with therapeutic payloads in cancer chemotherapy could be concluded. Nevertheless, more comprehensive studies are required to understand the exact intracellular and systemic fate of these nano-carriers, as well as their clinical efficacy for cancer treatment.

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