scholarly journals 161. Development of a Novel Low Toxicity and High Efficiency PEI-Based Nanopolymer for Gene Delivery In Vitro and In Vivo

2009 ◽  
Vol 17 ◽  
pp. S64 ◽  
Acta Naturae ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 20-30 ◽  
Author(s):  
E. P. Goncharova ◽  
Y. A. Kostyro ◽  
A. V. Ivanov ◽  
M. A. Zenkova

The development of novel drugs against the influenza virus with high efficiency and low toxicity is an urgent and important task. Previous reports have demonstrated that compounds based on sulfo derivatives of oligo- and polysaccharides possess high antiviral activity. In this study, we have examined the ability of a novel sulfonated derivative of -cyclodextrin (KS-6469) to inhibit the influenza virus A/WSN/33 (H1N1) infection in vitro and in vivo. The antiviral potential of KS-6469 against the influenza virus was evaluated in Madin-Darby Canine Kidney epithelial cells treated with serially diluted KS-6469. We found out that KS-6469 completely inhibited viral reproduction after treatment of the infected cells with the compound for 48 h. Our data show that double intranasal treatment of mice with KS-6469 fully protected the animals from a lethal infection and significantly decreased the viral titers in the lungs of the infected animals. Thus, the novel sulfonated -cyclodextrin derivative KS-6469 is a promising candidate for the development of antiviral drugs for preventing and treating the influenza infection.


Author(s):  
Qiongjie Ding ◽  
Yiwei Liu ◽  
Chuncheng Shi ◽  
Jifei Xiao ◽  
Wei Dai ◽  
...  

Background: Metal-organic frameworks (MOFs) exhibited the adjustable aperture, high load capacities, tailorable structures, and excellent biocompatibilities that have used to be as drug delivery carries in cancer therapy. Until now, Zr-MOFs in particular combine optimal stability towards hydrolysis and postsynthetic modification with low toxicity, and are widely studied for its excellent biological performance. Introduction: This review comprises the exploration of Zr-MOFs as drug delivery devices (DDSs) with focus on various new methods, including chemotherapy (CT), photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy(SDT), radiotherapy, immunotherapy, gene therapy and related combined therapies, which all generate reactive oxygen species (ROS) to achieve the high efficiency of tumor therapy. Conclusion: We described and summarized these pertinent examples of the therapeutic mechanisms and highlight the antitumor effects of their biological application both in vitro and in vivo. The perspectives on their future applications and analogous challenge of the Zr-MOFs materials are given.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 171 ◽  
Author(s):  
Xiaoshuang Guo ◽  
Zihan Yuan ◽  
Yang Xu ◽  
Xiaotian Zhao ◽  
Zhiwei Fang ◽  
...  

Peripheral arterial disease (PAD) is often characterized by continued reduction in blood flow supply to limbs. Advanced therapeutic strategies like gene therapy could potentially be applied to limb ischemia therapy. However, developing a gene delivery system with low toxicity and high efficiency remains a great challenge. In this study, a one-pot construction was used to integrate vector synthesis and polyplex fabrication simultaneously in a simple and robust manner. We fabricated an interpenetrating gene delivery network through the physical interaction between low-molecular-weight polyethylenimine (PEI 1.8 kDa) and plasmid DNA (pDNA) and the chemical bonding between PEI and glutaraldehyde (GA), which was named the glutaraldehydelinked-branched PEI (GPEI) polyplex. The final GPEI polyplex system was pH-responsive and biodegradable due to the imine linkage and it could successfully deliver desired vascular endothelial growth factor (VEGF) pDNA. Compared with PEI (25 kDa)/pDNA polyplexes, GPEI polyplexes showed lower cytotoxicity and higher transfection efficiency both in vitro and in vivo. In addition, we demonstrated that GPEI polyplexes could efficiently promote the formation of new capillaries in vivo, which may provide a practicable strategy for clinical hindlimb ischemia therapy in the future.


2021 ◽  
Vol 18 ◽  
Author(s):  
Xinghua Zhao ◽  
Shi Ding ◽  
Shengnan Li ◽  
Yang Wang ◽  
Mingjun Jiang ◽  
...  

Purpose: An active-passive dual-targeting gambogic acid HPMA Copolymer Coupling drug system with high efficiency, low toxicity and high selectivity was constructed. Methods: The gambogic acid HPMA copolymer coupling drug system was constructed and its structure was characterized. The cytotoxicity of gambogic acid HPMA copolymer was detected by MTT assay. The pharmacokinetics of gambogic acid HPMA copolymer was evaluated in mice. Targetability of gambogic acid HPMA copolymer was evaluated by tissue distribution experiment. The in vitro antitumor activity of gambogic acid HPMA copolymer was evaluated by pharmacodynamics experiment in mice. Results : Two copolymers of gambogic acid HPMA were successfully prepared. The copolymers showed reduced cytotoxicity and a certain sustained release effect and targeting property. In vivo pharmacodynamic experiments also showed better anti-tumor effects than GA. Discussion: In this study, gambogic acid was combined with HPMA polymer and the targeting molecule D-galactose/folic acid to form a polymer micelle with high efficiency, low toxicity and high selectivity for active-passive dual targeting. The construction of the drug system provides new ideas for future formulation research and development.


Drug Delivery ◽  
2017 ◽  
Vol 25 (1) ◽  
pp. 122-131 ◽  
Author(s):  
Linjiang Song ◽  
Xiuqi Liang ◽  
Suleixin Yang ◽  
Ning Wang ◽  
Tao He ◽  
...  

2014 ◽  
Vol 13 (1) ◽  
pp. 110-115
Author(s):  
Ye. V. Razmakhnin ◽  
S. L. Lobanov ◽  
O. G. Konovalova

For the treatment of calculouscholecystitis in patients with high-risk surgery in the treatment of choledocholithiasis in an effort to preserve the sphincter apparatus major duodenal papilla are encouraged to use the contact litholysis gallstones saxifragant mixture of octanoic acid – glycerol in a ratio of 1 : 1.The possibility of dissolution of stones in experiments in vitro (n = 51) and in vivo (n = 35), confirmed the low toxicity and high efficiency of the proposed technique. In vitro experiments, for more convenient evaluation was introduced conditional coefficient (K) that reflects the time lithodialysis in minutes per 1 mg of the stone weight. In experiments in vitro: K' = 5.76 (n = 51). It is noted that in the group of stones with low mineralization using saxifragant mixture K' = 4.50 (n = 15), with an average K' = 5.76 (n = 17), high K' = 6.88 (n = 19).In an in vivo experiment used 35 sexually mature rabbits after modeling cholelithiasischolecystitis was made through the introduction of a mixture of saxifragant rate of 0.2 ml/kg body weight once a day. Lowmineralized stones disappeared in all cases (after the double administration) medium mineralizedwhen administered for 3 days or more, the highly mineralized 4 – day of treatment. After treatment, histologically and biochemically, were found pronounced toxic effects of the drug.The clinic is possible to impose mikroholetsistostomy under ultrasound gui dance, irrigation lumen of the gall bladder, treatment of acute inflammation, followed by solvent solubility and control of stones with ultrasound studies, or using fistuloholangiografiyu. When choledocholithiasis, especially when residual common bile duct stones in an effort to preserve the sphincter apparatus ma jor duodenal papilla, possibly through the introduction of a mixture of saxifragant hepaticocholedochus established percutaneously transhepatic under ultrasound guidance, either through drainage nazobi liarny established endoscopically through major duodenal papilla. The advantages of this method compared to peers is less toxic solvent, speed lysing effect, the efficiency of the process calculi with different composition (cholesterol and pigment). Compared with the traditional methods of trea tment of gallstone disease differs minimally invasive and thus significantly reduces the risk of intra -and postoperative complications, both local and general, and significantly shorten the treatment of patients and their stay in hospital.


2020 ◽  
Vol 20 (11) ◽  
pp. 821-830
Author(s):  
Prasad Pofali ◽  
Adrita Mondal ◽  
Vaishali Londhe

Background: Current gene therapy vectors such as viral, non-viral, and bacterial vectors, which are used for cancer treatment, but there are certain safety concerns and stability issues of these conventional vectors. Exosomes are the vesicles of size 40-100 nm secreted from multivesicular bodies into the extracellular environment by most of the cell types in-vivo and in-vitro. As a natural nanocarrier, exosomes are immunologically inert, biocompatible, and can cross biological barriers like the blood-brain barrier, intestinal barrier, and placental barrier. Objective: This review focusses on the role of exosome as a carrier to efficiently deliver a gene for cancer treatment and diagnosis. The methods for loading of nucleic acids onto the exosomes, advantages of exosomes as a smart intercellular shuttle for gene delivery and therapeutic applications as a gene delivery vector for siRNA, miRNA and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and also the limitations of exosomes as a gene carrier are all reviewed in this article. Methods: Mostly, electroporation and chemical transfection are used to prepare gene loaded exosomes. Results: Exosome-mediated delivery is highly promising and advantageous in comparison to the current delivery methods for systemic gene therapy. Targeted exosomes, loaded with therapeutic nucleic acids, can efficiently promote the reduction of tumor proliferation without any adverse effects. Conclusion: In the near future, exosomes can become an efficient gene carrier for delivery and a biomarker for the diagnosis and treatment of cancer.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Lu Wang ◽  
Shuwei Liu ◽  
Chunxia Ren ◽  
Siyuan Xiang ◽  
Daowei Li ◽  
...  

AbstractNanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jie Zheng ◽  
Na Tian ◽  
Fei Liu ◽  
Yidian Zhang ◽  
Jingfen Su ◽  
...  

AbstractIntraneuronal accumulation of hyperphosphorylated tau is a hallmark pathology shown in over twenty neurodegenerative disorders, collectively termed as tauopathies, including the most common Alzheimer’s disease (AD). Therefore, selectively removing or reducing hyperphosphorylated tau is promising for therapies of AD and other tauopathies. Here, we designed and synthesized a novel DEPhosphorylation TArgeting Chimera (DEPTAC) to specifically facilitate the binding of tau to Bα-subunit-containing protein phosphatase 2A (PP2A-Bα), the most active tau phosphatase in the brain. The DEPTAC exhibited high efficiency in dephosphorylating tau at multiple AD-associated sites and preventing tau accumulation both in vitro and in vivo. Further studies revealed that DEPTAC significantly improved microtubule assembly, neurite plasticity, and hippocampus-dependent learning and memory in transgenic mice with inducible overexpression of truncated and neurotoxic human tau N368. Our data provide a strategy for selective removal of the hyperphosphorylated tau, which sheds new light for the targeted therapy of AD and related-tauopathies.


FEBS Letters ◽  
2001 ◽  
Vol 504 (3) ◽  
pp. 99-103 ◽  
Author(s):  
Kenneth Lundstrom ◽  
Christophe Schweitzer ◽  
Daniel Rotmann ◽  
Danielle Hermann ◽  
Edith M. Schneider ◽  
...  

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