Design of Virus-Mimicking Polyelectrolyte Complexes for Enhanced Oral Insulin Delivery

Liu, Chang; Xu, Hong‐Xi; Sun, Ying; Zhang, Xin; Cheng, Hongbo; Mao, Shirui

doi:10.1016/j.xphs.2019.05.034

Cited by 20 publications

(13 citation statements)

References 32 publications

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“…This was probably a result of the difference in the HbA1c‐lowering effect observed across the two studies, although a difference in the mechanism of action of ORMD‐0801 may also have been responsible for this. Numerous approaches to create oral insulin have been reported in recent years, but to the best of our knowledge, all are in early preclinical or clinical stages of development (including utilization of microparticles, microcapsules and microspheres, use of protease inhibitors, lipid nanocarriers, protein‐stabilized multiple emulsion with permeation enhancers, nanocomposite system of organoclay/glycol chitosan/Eudragit([R])S100, inclusion complex based on N‐acetyl‐L‐cysteine and arginine‐modified hydroxypropyl‐beta‐cyclodextrin, virus‐mimicking polyelectrolyte complexes and Zein‐based nanocarriers, amongst others) 19‐27 …”

Section: Discussionmentioning

confidence: 99%

“…Numerous approaches to create oral insulin have been reported in recent years, but to the best of our knowledge, all are in early preclinical or clinical stages of development (including utilization of microparticles, microcapsules and microspheres, use of protease inhibitors, lipid nanocarriers, protein-stabilized multiple emulsion with permeation enhancers, nanocomposite system of organoclay/glycol chitosan/Eudragit([R])S100, inclusion complex based on N-acetyl-L-cysteine and arginine-modified hydroxypropylbeta-cyclodextrin, virus-mimicking polyelectrolyte complexes and Zein-based nanocarriers, amongst others). [19][20][21][22][23][24][25][26][27] The strengths of the current study include its randomized, double-blind design and comparatively large sample size. Its limitations include the short washout period, the comparatively short exposure period and lack of ORMD-0801 dose titration.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy and safety of 28‐day treatment with oral insulin (ORMD‐0801) in patients with type 2 diabetes: A randomized, placebo‐controlled trial

Eldor

Neutel

Homer³

et al. 2021

Diabetes Obesity Metabolism

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Aim To assess the safety and efficacy of oral insulin (ORMD‐0801) in patients with type 2 diabetes (T2D). Materials and Methods After a 2‐week washout of other medications, adult metformin‐treated patients with T2D were randomized to receive placebo or 16 or 24 mg ORMD‐0801, once daily, at bedtime, for 28 days. The mean change from baseline weighted mean night‐time glucose levels was determined from 2 nights of continuous glucose monitoring (CGM) recordings during the placebo run‐in and last week of treatment. Results In total, 188 patients (HbA1c: 7.82% ± 0.88% [placebo] and 8.08% ± 1.11% [pooled ORMD‐0801 group]) were enrolled. In the placebo group, mean night‐time CGM increased from baseline by 13.7 ± 26.1 mg/dL, whereas the increase was significantly smaller in the pooled ORMD‐0801 group (1.7 ± 23.5 mg/dL, P = .0120). Glycaemic control variables (24‐hour, fasting and daytime CGM glucose) also displayed smaller increases with ORMD‐0801 versus placebo. Change from baseline HbA1c was −0.01% in the pooled ORMD‐0801 group versus +0.20% in the placebo group (P = .0149). ORMD‐0801 was well tolerated, with similar adverse event and hypoglycaemia rates as placebo. Conclusions In patients with T2D, bedtime ORMD‐0801 curbed increases in night‐time glycaemia, 24‐hour glycaemia and HbA1c, without increasing the risk of hypoglycaemia or safety events compared with the control arm.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of 28‐day treatment with oral insulin (ORMD‐0801) in patients with type 2 diabetes: A randomized, placebo‐controlled trial

Eldor

Neutel

Homer³

et al. 2021

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

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“…The epithelial cell barrier is located under the mucous barrier and reduces drug absorption from the gut lumen into the bloodstream through the paracellular or transcellular route. To overcome these barriers, the permeation of oral delivery devices needs to be improved, which can be achieved by learning from the mechanisms that bacteria and viruses apply to invade their host [139][140][141][142] .…”

Section: Bioinspired Permeationmentioning

confidence: 99%

Bioinspired oral delivery devices

et al. 2023

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Oral administration is a widespread and convenient drug delivery approach. However, oral delivery can be affected by the complex digestive tract environment, including irregular tissue morphology, the presence of digestive enzymes, mucus and mucosal barriers, and spatiotemporal variance in physiological parameters. These obstacles can prevent the oral delivery of many therapeutics. To overcome these challenges, oral delivery devices can be designed with bioinspired compositions, structures or functions to make more drugs available for oral administration. Various bioinspired oral delivery devices have been developed by harnessing biological materials and living microorganisms, or by imitating biological structures and functions. In this Review, we discuss the design and modification of bioinspired oral delivery devices, examining engineering strategies to target specific tissues and applications. We highlight how key bottlenecks in oral delivery can be addressed through bioinspired designs, concluding with an outlook on the remaining challenges towards the clinical translation of bioinspired oral delivery devices. SectionsIntroduction Naturally derived oral delivery devices Bioinspired oral delivery Target tissues Outlook

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“…The porous inorganic carrier materials were prepared to encapsulate insulin through the size difference between insulin and digestive enzyme, which could prevent the degradation of insulin by digestive enzyme. At the same time, the digestive enzymes could also be shielded by the hydrophobic interaction between the carrier materials and the digestive enzymes [ 48 , 49 , 50 , 51 ].…”

Section: Physiological Absorption Barrier Of Oral Insulinmentioning

confidence: 99%

Versatile Oral Insulin Delivery Nanosystems: From Materials to Nanostructures

Wang

Ren

et al. 2022

IJMS

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Diabetes is a chronic metabolic disease characterized by lack of insulin in the body leading to failure of blood glucose regulation. Diabetes patients usually need frequent insulin injections to maintain normal blood glucose levels, which is a painful administration manner. Long-term drug injection brings great physical and psychological burden to diabetic patients. In order to improve the adaptability of patients to use insulin and reduce the pain caused by injection, the development of oral insulin formulations is currently a hot and difficult topic in the field of medicine and pharmacy. Thus, oral insulin delivery is a promising and convenient administration method to relieve the patients. However, insulin as a peptide drug is prone to be degraded by digestive enzymes. In addition, insulin has strong hydrophilicity and large molecular weight and extremely low oral bioavailability. To solve these problems in clinical practice, the oral insulin delivery nanosystems were designed and constructed by rational combination of various nanomaterials and nanotechnology. Such oral nanosystems have the advantages of strong adaptability, small size, convenient processing, long-lasting pharmaceutical activity, and drug controlled-release, so it can effectively improve the oral bioavailability and efficacy of insulin. This review summarizes the basic principles and recent progress in oral delivery nanosystems for insulin, including physiological absorption barrier of oral insulin and the development of materials to nanostructures for oral insulin delivery nanosystems.

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Design of Virus-Mimicking Polyelectrolyte Complexes for Enhanced Oral Insulin Delivery

Cited by 20 publications

References 32 publications

Efficacy and safety of 28‐day treatment with oral insulin (ORMD‐0801) in patients with type 2 diabetes: A randomized, placebo‐controlled trial

Efficacy and safety of 28‐day treatment with oral insulin (ORMD‐0801) in patients with type 2 diabetes: A randomized, placebo‐controlled trial

Bioinspired oral delivery devices

Versatile Oral Insulin Delivery Nanosystems: From Materials to Nanostructures

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