葡萄糖氧化酶介导的智能响应胰岛素递送的研究进展

杨静如; 马俞宏; 黄德春; 钱红亮; 陈维

doi:10.11665/j.issn.1000-5048.20210603

葡萄糖氧化酶介导的智能响应胰岛素递送的研究进展

中国药科大学工学院制药工程教研室，南京 211198

基金项目: 国家自然科学基金资助项目（No.51973233）

计量
- 文章访问数: 289
- HTML全文浏览量: 27
- PDF下载量: 739
出版历程
- 收稿日期: 2021-08-07
- 修回日期: 2021-10-25
- 刊出日期: 2021-12-24

Progress of intelligent-responsive insulin delivery mediated by glucose oxidase

Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 211198, China

Funds: This study was supported by the National Natural Science Foundation of China (No.51973233)

摘要

摘要: 外源性胰岛素的递送对于1型和晚期2型糖尿病的治疗至关重要。传统的注射式给药易引发低血糖，而智能胰岛素系统具有安全、长效、高响应性等优点。葡萄糖氧化酶（glucose oxidase，GOx）能够消耗O₂，催化葡萄糖生成葡萄糖酸和H₂O₂，因此GOx系统的O₂水平、H₂O₂含量及pH大小与系统中的葡萄糖水平密切相关。本文总结了近年关于GOx在闭环胰岛素递送系统中的应用，按照机制分为pH响应、缺氧响应、H₂O₂响应的单一响应及多重响应，并探讨了GOx在未来应用方面所面临的机遇与挑战。
- 葡萄糖氧化酶 /
- 葡萄糖响应 /
- 胰岛素递送 /
- 糖尿病治疗 /
- 进展
Abstract: The delivery of exogenous insulin is very important for the treatment of type 1 and advanced type 2 diabetes.Traditional injectable administration is prone to cause hypoglycemia, while the intelligent insulin system has the advantages of safety, long-term effectiveness, and high responsiveness.Glucose oxidase (GOx) can consume O₂ and catalyze glucose to produce gluconic acid and H₂O₂.Therefore, the O₂ level, H₂O₂ content and pH of GOx system are closely related to the glucose level in the system.This review introduces the application of GOx in closed-loop insulin delivery systems at home and abroad in recent years, which can be divided into single response and multiple response of pH-response, hypoxia-response, and H₂O₂-response according to the mechanism.It also discusses the opportunities and challenge facing by the application of GOx in the future.
- glucose oxidase /
- glucose response /
- insulin delivery /
- diabetes treatment /
- advances

HTML全文

参考文献(63)

[1]	. J China Pharm Univ （中国药科大学学报），2011，42（2）：97-106.
[2]	van Dieren S，Beulens JWJ，van der Schouw YT，et al. The global burden of diabetes and its complications：an emerging pandemic［J］. Eur J Cardiovasc Prev Rehabilitation，2010，17（Suppl 1）：S3-S8.
[3]	Frizziero L，Calciati A，Torresin T，et al. Diabetic macular edema treated with 577-nm subthreshold micropulse laser：a real-life，long-term study［J］. J Pers Med，2021，11（5）：405.
[4]	Ma RJ，Shi LQ. Phenylboronic acid-based glucose-responsive polymeric nanoparticles：synthesis and applications in drug delivery［J］. Polym Chem，2014，5（5）：1503-1518.
[5]	Li CY，Huang WL，Qian H. Advances in the research of long-acting strategy of insulin and GLP-1 analogs［J］. J China Pharm Univ （中国药科大学学报），2018，49（6）：660-670.
[6]	Chai ZH，Dong HY，Sun XY，et al. Development of glucose oxidase-immobilized alginate nanoparticles for enhanced glucose-triggered insulin delivery in diabetic mice［J］. Int J Biol Macromol，2020，159：640-647.
[7]	Mo R，Jiang TY，Di J，et al. Emerging micro- and nanotechnology based synthetic approaches for insulin delivery［J］. Chem Soc Rev，2014，43（10）：3595-3629.
[8]	Wang J，Wang Z，Yu J，et al. Glucose-responsive insulin and delivery systems：innovation and translation［J］. Adv Mater，2020，32（13）：e1902004.
[9]	Ravaine V，Ancla C，Catargi B. Chemically controlled closed-loop insulin delivery［J］. J Control Release，2008，132（1）：2-11.
[10]	Wu Q，Wang L，Yu H，et al. Organization of glucose-responsive systems and their properties［J］. Chem Rev，2011，111（12）：7855-7875.
[11]	Zhao L，Wang L，Zhang Y，et al. Glucose oxidase-based glucose-sensitive drug delivery for diabetes treatment［J］. Polymers （Basel），2017，9（7）. DOI：10.3390/polym9070255.
[12]	Zhang M，Song CC，Du FS，et al. Supersensitive oxidation-responsive biodegradable PEG hydrogels for glucose-triggered insulin delivery［J］. ACS Appl Mater Interfaces，2017，9（31）：25905-25914.
[13]	Dong Y，Wang W，Veiseh O，et al. Injectable and glucose-responsive hydrogels based on boronic acid-glucose complexation［J］. Langmuir，2016，32（34）：8743-8747.
[14]	Liu XY，Li C，Lv J，et al. Glucose and H₂O₂ dual-responsive polymeric micelles for the self-regulated release of insulin［J］. ACS Appl Bio Mater，2020，3（3）：1598-1606.
[15]	Gordijo CR，Koulajian K，Shuhendler AJ，et al. Nanotechnology-enabled closed loop insulin delivery device：in vitro and in vivo evaluation of glucose-regulated insulin release for diabetes control［J］. Adv Funct Mater，2011，21（1）：73-82.
[16]	Wu Z，Zhang S，Zhang X，et al. Phenylboronic acid grafted chitosan as a glucose-sensitive vehicle for controlled insulin release［J］. J Pharm Sci，2011，100（6）：2278-2286.
[17]	Gu Z，Dang TT，Ma M，et al. Glucose-responsive microgels integrated with enzyme nanocapsules for closed-loop insulin delivery［J］. ACS Nano，2013，7（8）：6758-6766.
[18]	Anirudhan TS，Nair AS，Nair SS. Enzyme coated beta-cyclodextrin for effective adsorption and glucose-responsive closed-loop insulin delivery［J］. Int J Biol Macromol，2016，91：818-827.
[19]	Kim MY，Kim J. Chitosan microgels embedded with catalase nanozyme-loaded mesocellular silica foam for glucose-responsive drug delivery［J］. ACS Biomater Sci Eng，2017，3（4）：572-578.
[20]	Di J，Yu JC，Ye YQ，et al. Engineering synthetic insulin-secreting cells using hyaluronic acid microgels integrated with glucose-responsive nanoparticles［J］. Cell Mol Bioeng，2015，8（3）：445-454.
[21]	Fu Y，Liu W，Wang LY，et al. Erythrocyte-membrane-camouflaged nanoplatform for intravenous glucose-responsive insulin delivery［J］. Adv Funct Mater，2018，28（41）：1802250.
[22]	Mohammadpour F，Hadizadeh F，Tafaghodi M，et al. Preparation，in vitro and in vivo evaluation of PLGA/chitosan based nano-complex as a novel insulin delivery formulation［J］. Int J Pharm，2019，572：118710.
[23]	Gu Z，Aimetti AA，Wang Q，et al. Injectable nano-network for glucose-mediated insulin delivery［J］. ACS Nano，2013，7（5）：4194-4201.
[24]	Zhao L，Xiao C，Wang L，et al. Glucose-sensitive polymer nanoparticles for self-regulated drug delivery［J］. Chem Commun （Camb），2016，52（49）：7633-7652.
[25]	Zhou X，Wu H，Long R，et al. Oral delivery of insulin with intelligent glucose-responsive switch for blood glucose regulation［J］. J Nanobiotechnology，2020，18（1）：96.
[26]	Tai W，Mo R，Di J，et al. Bio-inspired synthetic nanovesicles for glucose-responsive release of insulin［J］. Biomacromolecules，2014，15（10）：3495-3502.
[27]	Zhou K，Wang Y，Huang X，et al. Tunable，ultrasensitive pH-responsive nanoparticles targeting specific endocytic organelles in living cells［J］. Angew Chem Int Ed Engl，2011，50（27）：6109-6114.
[28]	Luo FQ，Chen GJ，Xu W，et al. Microneedle-array patch with pH-sensitive formulation for glucose-responsive insulin delivery［J］. Nano Res，2021，14（8）：2689-2696.
[29]	Tong ZZ，Zhou JY，Huang RS，et al. Dual-responsive supramolecular self-assembly of inclusion complex of an azobenzene-ended poly（ε-caprolactone） with a water-soluble pillar［6］Arene and its application in controlled drug release［J］. J Polym Sci Part A：Polym Chem，2017，55（15）：2477-2482.
[30]	Zuo M，Qian W，Xu Z，et al. Multiresponsive supramolecular theranostic nanoplatform based on pillar［5］Arene and diphenylboronic acid derivatives for integrated glucose sensing and insulin delivery［J］. Small，2018，14（38）：e1801942.
[31]	Lin YH，Hu W，Bai XW，et al. Glucose- and pH-responsive supramolecular polymer vesicles based on host-guest interaction for transcutaneous delivery of insulin［J］. ACS Appl Bio Mater，2020，3（9）：6376-6383.
[32]	Ma RJ，Sun XC，Liu XJ，et al. Complex micelles with glucose-responsive shells for self-regulated release of glibenclamide［J］. Aust J Chem，2014，67（1）：127.
[33]	Gaballa H，Theato P. Glucose-responsive polymeric micelles via boronic acid-diol complexation for insulin delivery at neutral pH［J］. Biomacromolecules，2019，20（2）：871-881.
[34]	Li X，Shang H，Wu W，et al. Glucose-responsive micelles for controlled insulin release based on transformation from amphiphilic to double hydrophilic［J］. J Nanosci Nanotechnol，2016，16（6）：5457-5463.
[35]	Chen Y，Li P，Modica JA，et al. Acid-resistant mesoporous metal-organic framework toward oral insulin delivery：protein encapsulation，protection，and release［J］. J Am Chem Soc，2018，140（17）：5678-5681.
[36]	Zhang C，Hong S，Liu MD，et al. pH-sensitive MOF integrated with glucose oxidase for glucose-responsive insulin delivery［J］. J Control Release，2020，320：159-167.
[37]	Yang XX，Feng P，Cao J，et al. Composition-engineered metal-organic framework-based microneedles for glucose-mediated transdermal insulin delivery［J］. ACS Appl Mater Interfaces，2020，12（12）：13613-13621.
[38]	Jamwal S，Ram B，Ranote S，et al. New glucose oxidase-immobilized stimuli-responsive dextran nanoparticles for insulin delivery［J］. Int J Biol Macromol，2019，123：968-978.
[39]	Zhang G，Ji Y，Li X，et al. Polymer-covalent organic frameworks composites for glucose and pH dual-responsive insulin delivery in mice［J］. Adv Healthc Mater，2020，9（14）：e2000221.
[40]	Chen WH，Luo GF，Vázquez-González M，et al. Glucose-responsive metal-organic-framework nanoparticles act as "Smart" sense-and-treat carriers ［J］. ACS Nano，2018，12（8）：7538-7545.
[41]	Patel A，Sant S. Hypoxic tumor microenvironment：opportunities to develop targeted therapies［J］. Biotechnol Adv，2016，34（5）：803-812.
[42]	Thambi T，Deepagan VG，Yoon HY，et al. Hypoxia-responsive polymeric nanoparticles for tumor-targeted drug delivery［J］. Biomaterials，2014，35（5）：1735-1743.
[43]	Yu JC，Qian CG，Zhang YQ，et al. Hypoxia and H₂O₂ dual-sensitive vesicles for enhanced glucose-responsive insulin delivery［J］. Nano Lett，2017，17（2）：733-739.
[44]	Yu JC，Zhang YQ，Ye YQ，et al. Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery［J］. Proc Natl Acad Sci USA，2015，112（27）：8260-8265.
[45]	Thambi T，Deepagan VG，Yoon HY，et al. Hypoxia-responsive polymeric nanoparticles for tumor-targeted drug delivery［J］. Biomaterials，2014，35（5）：1735-1743.
[46]	Matsumoto A，Ishii T，Nishida J，et al. A synthetic approach toward a self-regulated insulin delivery system［J］. Angew Chem Int Ed Engl，2012，51（9）：2124-2128.
[47]	Bratlie KM，York RL，Invernale MA，et al. Materials for diabetes therapeutics［J］. Adv Healthc Mater，2012，1（3）：267-284.
[48]	Ye YQ，Yu JC，Wang C，et al.Microneedles integrated with pancreatic cells and synthetic glucose-signal amplifiers for smart insulin delivery ［J］. Adv Mater，2016，28（16）：3115-3121.
[49]	Yao Y，Zhao LY，Yang JJ，et al. Glucose-responsive vehicles containing phenylborate ester for controlled insulin release at neutral pH［J］. Biomacromolecules，2012，13（6）：1837-1844.
[50]	Wang J，Ye Y，Yu J，et al. Core-shell microneedle gel for self-regulated insulin delivery［J］. ACS Nano，2018，12（3）：2466-2473.
[51]	Huang Q，Wang L，Yu H，et al. Advances in phenylboronic acid-based closed-loop smart drug delivery system for diabetic therapy［J］. J Control Release，2019，305：50-64.
[52]	Hu XL，Yu JC，Qian CG，et al. H₂O₂-responsive vesicles integrated with transcutaneous patches for glucose-mediated insulin delivery［J］. ACS Nano，2017，11（1）：613-620.
[53]	Hei MY，Wu HJ，Fu Y，et al. Phenylboronic acid functionalized silica nanoparticles with enlarged ordered mesopores for efficient insulin loading and controlled release［J］. J Drug Deliv Sci Technol，2019，51：320-326.
[54]	Xu B，Jiang G，Yu W，et al. H₂O₂-Responsive mesoporous silica nanoparticles integrated with microneedle patches for the glucose-monitored transdermal delivery of insulin［J］. J Mater Chem B，2017，5（41）：8200-8208.
[55]	Yoshida K，Awaji K，Shimizu S，et al. Preparation of microparticles capable of glucose-induced insulin release under physiological conditions［J］. Polymers，2018，10（10）：1164.
[56]	Tong ZZ，Zhou JY，Zhong JX，et al. Glucose- and H₂O₂-responsive polymeric vesicles integrated with microneedle patches for glucose-sensitive transcutaneous delivery of insulin in diabetic rats［J］. ACS Appl Mater Interfaces，2018，10（23）：20014-20024.
[57]	Wang YX，Fan YT，Zhang MH，et al. Glycopolypeptide nanocarriers based on dynamic covalent bonds for glucose dual-responsiveness and self-regulated release of insulin in diabetic rats［J］. Biomacromolecules，2020，21（4）：1507-1515.
[58]	Hou L，Zheng YZ，Wang YC，et al. Self-regulated carboxyphenylboronic acid-modified mesoporous silica nanoparticles with “touch switch” releasing property for insulin delivery［J］. ACS Appl Mater Interfaces，2018，10（26）：21927-21938.
[59]	Zhang Y，Wang J，Yu J，et al. Bioresponsive microneedles with a sheath structure for H₂O₂ and pH cascade-triggered insulin delivery［J］. Small，2018，14（14）：e1704181.
[60]	Liu F，Bai L，Zhang H，et al. Smart H₂O₂-responsive drug delivery system made by halloysite nanotubes and carbohydrate polymers［J］. ACS Appl Mater Interfaces，2017，9（37）：31626-31633.
[61]	Shen D，Yu HJ，Wang L，et al. Glucose-responsive hydrogel-based microneedles containing phenylborate ester bonds and N-isopropylacrylamide moieties and their transdermal drug delivery properties［J］. Eur Polym J，2021，148：110348.
[62]	Wang C，Ye YQ，Sun WJ，et al. Red blood cells for glucose-responsive insulin delivery［J］. Adv Mater，2017，29（18）：1606617.
[63]	Sokolovska J，Isajevs S，Baumane L，et al. Enhanced expression of xanthine oxidase and NO synthases causing the overproduction of NO in kidneys of diabetic animals can be reduced by 1，4-dihydropyridines［J］. Nitric Oxide，2013，31：S15.