Construction of gambogic acid HPMA Copolymer Coupling drug system and study on anti-tumor activity

2021 ◽  
Vol 18 ◽  
Author(s):  
Xinghua Zhao ◽  
Shi Ding ◽  
Shengnan Li ◽  
Yang Wang ◽  
Mingjun Jiang ◽  
...  
Keyword(s):  
High Selectivity ◽  
High Efficiency ◽  
Gambogic Acid ◽  
Polymer Micelle ◽  
Hpma Copolymer ◽  
Dual Targeting ◽  
New Ideas ◽  
Low Toxicity

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.

scholarly journals A Novel Sulfonated Derivative of β-Cyclodextrin Effectively Inhibits Influenza A Virus Infection in vitro and in vivo

Acta Naturae ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 20-30 ◽  
Author(s):  
E. P. Goncharova ◽  
Y. A. Kostyro ◽  
A. V. Ivanov ◽  
M. A. Zenkova
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
High Efficiency ◽  
Influenza Infection ◽  
Lethal Infection ◽  
Novel Drugs ◽  
Infected Cells ◽  
Low Toxicity

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.

Applications of ROS-Induced Zr-MOFs Platform in Multimodal Synergistic Therapy

2021 ◽  
Vol 21 ◽  
Author(s):  
Qiongjie Ding ◽  
Yiwei Liu ◽  
Chuncheng Shi ◽  
Jifei Xiao ◽  
Wei Dai ◽  
...  
Keyword(s):  
Drug Delivery ◽  
High Efficiency ◽  
Tumor Therapy ◽  
Antitumor Effects ◽  
Metal Organic ◽  
Low Toxicity ◽  
Therapeutic Mechanisms ◽  
Biological Performance

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.

scholarly journals OPPORTUNITIES OF CONTACT LITHOLYSIS IN THE TREATMENT OF GALLSTONE DISEASE

2014 ◽  
Vol 13 (1) ◽  
pp. 110-115
Author(s):  
Ye. V. Razmakhnin ◽  
S. L. Lobanov ◽  
O. G. Konovalova
Keyword(s):  
High Efficiency ◽  
Gallstone Disease ◽  
Common Bile Duct Stones ◽  
Duodenal Papilla ◽  
Major Duodenal Papilla ◽  
High K ◽  
Low Toxicity ◽  
And Control

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.

scholarly journals Construction of hollow polydopamine nanoparticle based drug sustainable release system and its application in bone regeneration

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Lu Wang ◽  
Shuwei Liu ◽  
Chunxia Ren ◽  
Siyuan Xiang ◽  
Daowei Li ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Defect ◽  
Load Capacity ◽  
Good Prospect ◽  
Alizarin Red ◽  
Drug Load ◽  
Load Rate ◽  
Low Toxicity

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.

scholarly journals A novel dephosphorylation targeting chimera selectively promoting tau removal in tauopathies

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jie Zheng ◽  
Na Tian ◽  
Fei Liu ◽  
Yidian Zhang ◽  
Jingfen Su ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Protein Phosphatase ◽  
High Efficiency ◽  
Microtubule Assembly ◽  
Hyperphosphorylated Tau ◽  
Phosphatase 2A ◽  
Dependent Learning ◽  
The Brain

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.

Evaluation of Paclitaxel Nanocrystals In Vitro and In Vivo

Drug Research ◽  
2017 ◽  
Vol 68 (04) ◽  
pp. 205-212 ◽  
Author(s):  
Wanqing Li ◽  
Zhiguo Li ◽  
Lisha Wei ◽  
Aiping Zheng
Keyword(s):  
Drug Concentration ◽  
Antitumor Effects ◽  
High Drug ◽  
High Drug Concentration ◽  
Low Toxicity ◽  
Nanoparticle Drug Delivery ◽  
Antitumor Evaluation ◽  
Mcf 7

AbstractWe created a novel paclitaxel (PTX) nanoparticle drug delivery system and compared this to acommercial injection preparation to evaluate the antitumor effects for both formulations in vivo and in vitro.PTXnanocrystals were 194.9 nm with potential of −29.6 mV. Cytotoxicity tests indicated that both formulations had similar effects and cytotoxicity was dose- and time-dependent.Pharmacodynamics indicated that the drug concentration at the tumor was greater with PTX nanocrystals compared to commercial injection (P<0.01) and that drug accumulated more and for a longer duration. In vivo antitumor evaluation indicated significant antitumor effects and low toxicity of PTX nanocrystals. Moreover, bioimaging indicated that the PTX retention time in MCF-7-bearing mice was longer, especially at the tumor site, and this high drug concentration was maintained for a long time.Overall, PTX nanocrystalsare feasible and superior to traditional injection formulation chemotherapy.

scholarly journals Recombinogenic Flap Ligation Pathway for Intrinsic Repair of Topoisomerase IB-Induced Double-Strand Breaks

2000 ◽  
Vol 20 (21) ◽  
pp. 8059-8068 ◽  
Author(s):  
Chonghui Cheng ◽  
Stewart Shuman
Keyword(s):  
High Efficiency ◽  
Strand Break ◽  
Strand Transfer ◽  
Strand Breaks ◽  
Genomic Deletions ◽  
Topoisomerase Ib ◽  
Dna Strand ◽  
Recombination Pathway

ABSTRACT Topoisomerase IB catalyzes recombinogenic DNA strand transfer reactions in vitro and in vivo. Here we characterize a new pathway of topoisomerase-mediated DNA ligation in vitro (flap ligation) in which vaccinia virus topoisomerase bound to a blunt-end DNA joins the covalently held strand to a 5′ resected end of a duplex DNA containing a 3′ tail. The joining reaction occurs with high efficiency when the sequence of the 3′ tail is complementary to that of the scissile strand immediately 5′ of the cleavage site. A 6-nucleotide segment of complementarity suffices for efficient flap ligation. Invasion of the flap into the duplex apparently occurs while topoisomerase remains bound to DNA, thereby implying a conformational flexibility of the topoisomerase clamp around the DNA target site. The 3′ flap acceptor DNA mimics a processed end in the double-strand-break-repair recombination pathway. Our findings suggest that topoisomerase-induced breaks may be rectified by flap ligation, with ensuing genomic deletions or translocations.

scholarly journals Exploring heteroaromatic rings as a replacement for the labile amide of antiplasmodial pantothenamides

2020 ◽  
Author(s):  
Jinming Guan ◽  
Christina Spry ◽  
Erick T. Tjhin ◽  
Penghui Yang ◽  
Tanakorn Kittikool ◽  
...  
Keyword(s):  
Contact Time ◽  
High Selectivity ◽  
Amide Group ◽  
Antiplasmodial Activity ◽  
Time Data ◽  
Facile Synthesis ◽  
Isoxazole Derivative ◽  
Nanomolar Range

ABSTRACTThe Plasmodium parasites that cause malaria are adept at developing resistance to antimalarial drugs, necessitating the search for new antiplasmodials. Although several amide analogs of pantothenate (pantothenamides) show potent antiplasmodial activity, hydrolysis by pantetheinases (or vanins) present in blood rapidly inactivates them. We report herein the facile synthesis and biological activity of a small library of pantothenamide analogs in which the labile amide group is replaced with a variety of heteroaromatic rings. Several of the new analogs display antiplasmodial activity in the nanomolar range against P. falciparum and/or P. knowlesi in the presence of pantetheinase. A previously reported triazole and an isoxazole derivative presented here were further characterized and found to possess high selectivity indices, medium or high Caco-2 permeability, and medium or low microsomal clearance in vitro. Although we show here that the two compounds fail to suppress proliferation of P. berghei in vivo, pharmacokinetic and contact time data presented provide a benchmark for the compound profile required to achieve antiplasmodial activity in mice and should facilitate lead optimization.

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