Oral insulin delivery by carboxymethyl-β-cyclodextrin-grafted chitosan nanoparticles for improving diabetic treatment

Song, Mingming; Wang, Hui; Chen, Kuanmin; Zhang, Song; Yu, Lizhen; Elshazly, Ezzat H.; Ke, Lixia; Gong, Renmin

doi:10.1080/21691401.2018.1511575

Cited by 49 publications

(14 citation statements)

References 33 publications

(41 reference statements)

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“…When the medium was changed from pH 2.0 to pH 6.8 (simulated intestinal fluid, SIF), due to the pH sensitivity of AC‐NPs, the drug release rate significantly increased to about 48.3% within 2 h. In the following 8 h, the release slowly increased to 70.9%, which may be caused by the swelling and dissolution of alginate nanoparticles in PBS buffer. Previous studies have also confirmed that insulin release was delayed under simulated gastric fluid and showed significant release at pH 6.8 of simulated intestinal fluid 34–36 …”

Section: Resultsmentioning

confidence: 71%

Microparticles based on alginate/chitosan/casein three‐dimensional system for oral insulin delivery

Chen

Duan

et al. 2021

Polymers for Advanced Techs

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In the past, oral insulin has been developed to reduce the suffering of diabetic patients. However, the physiological barriers in gastrointestinal (GI) tract are the major challenges in oral delivery of insulin. In this study, a novel oral delivery system of insulin called NiM (NPs in MPs) has been developed to overcome the GI barriers, which based on a three‐dimensional system of biocompatible chitosan/alginate/casein. Alginate/chitosan nanoparticles (AC‐NPs) were firstly prepared by ionic pre‐gel method and complexation with polyelectrolytes. Then, they were subsequently coated with casein as a protective agent to form NiM, which could keep stability and physiological activity of insulin in gastric tract. The characterization of NiM showed stable hydrodynamic parameters, and the entrapment efficiency of insulin reached 51.1%. In vitro, only 13.5% of insulin was released in the simulated gastric fluid for the first 2 h. But about 57.4% of insulin was slowly released in the simulated intestinal fluid for 10 h. These results indicated that the coating of casein could increase stability of insulin in gastric tract and control release of insulin in intestinal tract. Furthermore, NiM provided a sustained and significant reduction of the blood glucose levels of diabetic mice. Overall, the results demonstrated that our formed NiM may be a promising oral delivery system of insulin for diabetic patients.

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Section: Resultsmentioning

confidence: 71%

Microparticles based on alginate/chitosan/casein three‐dimensional system for oral insulin delivery

Chen

Duan

et al. 2021

Polymers for Advanced Techs

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“…In diabetic disease, for a better function of oral insulin administration, Song et al, in 2018, fabricated carboxymethyl-β-cyclodextrin-grafted chitosan nanoparticles (insulin-CMCD-g-CS NPs) via the ionic crosslinking method. The result of the study demonstrated that the oral administration of insulin-loaded CMC-g-CS nanoparticles declined the level of blood sugar in the mice model [ 152 ]. In addition, CD-NSs were proposed as insulin carriers too [ 153 ].…”

Section: Cyclodextrin Monomers and Polymers As An Enhancer Of The Drug Effectmentioning

confidence: 99%

Cyclodextrin Monomers and Polymers for Drug Activity Enhancement

et al. 2021

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Cyclodextrins (CDs) and cyclodextrin (CD)-based polymers are well-known complexing agents. One of their distinctive features is to increase the quantity of a drug in a solution or improve its delivery. However, in certain instances, the activity of the solutions is increased not only due to the increase of the drug dose but also due to the drug complexation. Based on numerous studies reviewed, the drug appeared more active in a complex form. This review aims to summarize the performance of CDs and CD-based polymers as activity enhancers. Accordingly, the review is divided into two parts, i.e., the effect of CDs as active drugs and as enhancers in antimicrobials, antivirals, cardiovascular diseases, cancer, neuroprotective agents, and antioxidants.

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“…Chitosan and CD were integrated together to prepare carboxymethyl-β-CD-grafted CS nanoparticles (CMCD-g-CS nanoparticles) via ionic gelation method [ 113 , 115 ]. Song et al, have synthesised CMCD-g-CS by EDC-mediated esterification reaction, then TPP solution was gradually added into the insulin/CMCDg-CS solution for 1 h under continuous stirring.…”

Section: Chitosan Modificationmentioning

confidence: 99%

“…A greater extent and higher insulin released was attainable in SIF with a cumulative amount higher than 80% over 1.5 h dissolution, achieving bioavailability of 14.54%. Insulin-CMCD-g-CS nanoparticles were advocated to be highly biocompatible with minimised cellular toxicity effects, where more than 80% cell viability has reported after incubating in nanoparticles solution at a concentration range of 20–120 µg/mL [ 115 ].…”

Section: Chitosan Modificationmentioning

confidence: 99%

Recent Progress of Chitosan and Chitosan Derivatives-Based Nanoparticles: Pharmaceutical Perspectives of Oral Insulin Delivery

2020

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Diabetes mellitus is a chronic endocrine disease, affecting more than 400 million people around the world. Patients with poorly controlled blood glucose levels are liable to suffer from life-threatening complications, such as cardiovascular, neuropathy, retinopathy and even premature death. Today, subcutaneous parenteral is still the most common route for insulin therapy. Oral insulin administration is favourable and convenient to the patients. In contrast to injection route, oral insulin delivery mimics the physiological pathway of endogenous insulin secretion. However, oral insulin has poor bioavailability (less than 2%) due to the harsh physiological environment through the gastrointestinal tract (GIT). Over the last few decades, many attempts have been made to achieve an effective oral insulin formulation with high bioavailability using insulin encapsulation into nanoparticles as advanced technology. Various natural polymers have been employed to fabricate nanoparticles as a delivery vehicle for insulin oral administration. Chitosan, a natural polymer, is extensively studied due to the attractive properties, such as biodegradability, biocompatibility, bioactivity, nontoxicity and polycationic nature. Numerous studies were conducted to evaluate chitosan and chitosan derivatives-based nanoparticles capabilities for oral insulin delivery. This review highlights strategies that have been applied in the recent five years to fabricate chitosan/chitosan derivatives-based nanoparticles for oral insulin delivery. A summary of the barriers hurdle insulin absorption rendering its low bioavailability such as physical, chemical and enzymatic barriers are highlighted with an emphasis on the most common methods of chitosan nanoparticles preparation. Nanocarriers are able to improve the absorption of insulin through GIT, deliver insulin to the blood circulation and lower blood glucose levels. In spite of some drawbacks encountered in this technology, chitosan and chitosan derivatives-based nanoparticles are greatly promising entities for oral insulin delivery.

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Oral insulin delivery by carboxymethyl-β-cyclodextrin-grafted chitosan nanoparticles for improving diabetic treatment

Cited by 49 publications

References 33 publications

Microparticles based on alginate/chitosan/casein three‐dimensional system for oral insulin delivery

Microparticles based on alginate/chitosan/casein three‐dimensional system for oral insulin delivery

Cyclodextrin Monomers and Polymers for Drug Activity Enhancement

Recent Progress of Chitosan and Chitosan Derivatives-Based Nanoparticles: Pharmaceutical Perspectives of Oral Insulin Delivery

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