Uricase alkaline enzymosomes with enhanced stabilities and anti-hyperuricemia effects induced by favorable microenvironmental changes

Zhou, Yunli; Zhang, Mi; He, Dongyi; Hu, Xueyuan; Xiong, Hua; Wu, Jianyong; Zhu, Biyue; Zhang, Jingqing

doi:10.1038/srep20136

Cited by 29 publications

(14 citation statements)

References 49 publications

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“…An enzyme with diverse applications in medicine and industry ranging from therapeutics and diagnosis to biosensors technology, namely urate oxidase, has been the subject of most research studies (Arora et al 2014;Cammalleri and Malaguarnera 2007;Kant et al 2016;Pasut et al 2008;Sherman et al 2008;Zhou et al 2016). The major drawback in protein utilization is mainly its conformational and kinetic stability weakness (De Laet et al 2016).…”

Section: Discussionmentioning

confidence: 99%

Recombinant production of Aspergillus Flavus uricase and investigation of its thermal stability in the presence of raffinose and lactose

Imani

Shahmohamadnejad

2017

3 Biotech

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Aspergillus flavus uricase (Rasburicase) with a molecular mass of 135 kDa is currently used for the treatment of gout and hyperuricemia occurring in tumor lysis syndrome. To characterize the effects of raffinose and lactose osmolytes on the uricase structure, its coding sequence was cloned, expressed in E. coli BL21, and purified by Ni-NTA agarose affinity chromatography. Thermal inactivation studies at 40 °C showed that nearly 15% of UOX activity was preserved, while the presence of raffinose and lactose reduced its activity to 35 and 45% of its original activity, respectively. Investigation of UOX thermal stability at 40 °C in the course of time showed that the enzyme relatively lost almost 60% of its original activity after 40 min, whereas more than 50% of UOX activity is preserved in the presence of lactose. Estimation of thermal inactivation rate constant, k , showed that the UOX k and UOX k in the presence of raffinose was unchanged (0.018 min), whereas for the presence of lactose, it was 0.015 min. Half-life and T analysis showed that UOX half-life is almost 38 min and addition of raffinose did not change the half-life, whereas the presence of lactose had remarkable impact on UOX half-life (46 min). The presence of raffinose increased UOX T to a lesser extent, whereas lactose notably enhanced the T from 27 to 37 °C. Overall, our findings show that lactose has protective effects on UOX stability, while for raffinose, it is relatively compromised.

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Section: Discussionmentioning

confidence: 99%

Recombinant production of Aspergillus Flavus uricase and investigation of its thermal stability in the presence of raffinose and lactose

Imani

Shahmohamadnejad

2017

3 Biotech

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“…The higher bioavailability was related to higher absorption, higher concentration over time, and lower clearance. The superior pharmacokinetic properties of EFEN definitely favored the production of therapeutic effects (Zhou et al., 2016 ). EFEN could be maintained in the tumor area via injection.…”

Section: Resultsmentioning

confidence: 99%

Improved delivery of natural alkaloids into lung cancer through woody oil-based emulsive nanosystems

Zhao

Liu

et al. 2018

Drug Delivery

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Most antitumor ingredients found in nature have poor solubility. These ingredients are expected to have much better absorption and higher bioavailability than synthetic antitumor agents. Woody oil emulsive nanosystems carrying poorly soluble natural alkaloids were fabricated (evodiamine (EA) carried by fructus bruceae oil-based emulsive nanosystems, or EFEN). Fructus bruceae oil has two excipient-like properties (oil phase and stabilizer) that contribute to the formulation and one drug-like property (antitumor effects) that synergizes with the antitumor effect of EA. The properties of EFEN were compared with free EA, a blank nanoemulsion, an EA-loaded emulsive nanosystem, and a fructus bruceae oil-loaded emulsive nanosystem. For the first time, this suggests that increases in the sensitivity of lung cancer cells to poorly soluble natural alkaloids can be achieved by delivering drugs using woody oil-based emulsive nanosystems. In this study, woody oil-based emulsive nanosystems efficiently deliver poorly soluble natural alkaloids.

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“…Phase II biotransformation (combination reaction) combines the polar groups produced by phase I with endogenous components in the body through covalent bonds. 23,44 The produced combination, possessing high polarity, is easy to dissolve in water and discharge from the body. Renal clearance is mainly controlled by membrane transport proteins and is an important elimination pathway for antiviral agents.…”

Section: Metabolic Enzyme Reaction and Metabolite Of Avdsmentioning

confidence: 99%

Antiviral Drug Delivery System for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics

Chen¹,

Wang²,

Song³

et al. 2021

IJN

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Antiviral drugs (AvDs) are the primary resource in the global battle against viruses, including the recent fight against corona virus disease 2019 . Most AvDs require multiple medications, and their use frequently leads to drug resistance, since they have poor oral bioavailability and low efficacy due to their low solubility/low permeability. Characterizing the in vivo metabolism and pharmacokinetic characteristics of AvDs may help to solve the problems associated with AvDs and enhance their efficacy. In this review of AvDs, we systematically investigated their structure-based metabolic reactions and related enzymes, their cellular pharmacology, and the effects of metabolism on AvD pharmacodynamics and pharmacokinetics. We further assessed how delivery systems achieve better metabolism and pharmacology of AvDs. This review suggests that suitable nanosystems may help to achieve better pharmacological activity and pharmacokinetic behavior of AvDs by altering drug metabolism through the utilization of advanced nanotechnology and appropriate administration routes. Notably, such AvDs as ribavirin, remdesivir, favipiravir, chloroquine, lopinavir and ritonavir have been confirmed to bind to the severe acute respiratory syndrome-like coronavirus (SARS-CoV-2) receptor and thus may represent anti-COVID-19 treatments. Elucidating the metabolic and pharmacokinetic characteristics of AvDs may help pharmacologists to identify new formulations with high bioavailability and efficacy and help physicians to better treat virus-related diseases, including COVID-19.

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Uricase alkaline enzymosomes with enhanced stabilities and anti-hyperuricemia effects induced by favorable microenvironmental changes

Cited by 29 publications

References 49 publications

Recombinant production of Aspergillus Flavus uricase and investigation of its thermal stability in the presence of raffinose and lactose

Recombinant production of Aspergillus Flavus uricase and investigation of its thermal stability in the presence of raffinose and lactose

Improved delivery of natural alkaloids into lung cancer through woody oil-based emulsive nanosystems

Antiviral Drug Delivery System for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics

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