Affordable oral proinsulin bioencapsulated in plant cells regulates blood sugar levels similar to natural insulin

Daniell, Henry; Singh, Rahul; Mangu, Venkata; Nair, Smruti K.; Wakade, Geetanjali; Balashova, Nataliya V.

doi:10.1016/j.biomaterials.2023.122142

Cited by 9 publications

(1 citation statement)

References 87 publications

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“…Hyperglycemia and hypoglycemia can develop, affecting health outcomes and reflecting the severity of sepsis. A fasting blood glucose level of 80–100 mg/dL has been reported for healthy, nondiabetic mice [ 11 , 12 ]. In the I.P.…”

Section: Main Textmentioning

confidence: 99%

Intraperitoneal versus intranasal administration of lipopolysaccharide in causing sepsis severity in a murine model: a preliminary comparison

Jiao,

Tong,

Zhao

et al. 2024

Lab Anim Res

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Community-acquired respiratory infection is the commonest cause of sepsis presenting to emergency departments. Yet current experimental animal models simulate peritoneal sepsis with intraperitoneal (I.P.) injection of lipopolysaccharide (LPS) as the predominant route. We aimed to compare the progression of organ injury between I.P. LPS and intranasal (I.N.) LPS in order to establish a better endotoxemia murine model of respiratory sepsis. Eight weeks old male BALB/c mice received LPS-Escherichia coli doses at 0.15, 1, 10, 20, 40 and 100 mg per kg body weight (e.g. LPS-10 is a dose of 10 mg/kg body weight). Disease severity was monitored by a modified Mouse Clinical Assessment Score for Sepsis (M-CASS; range 0–21). A M-CASS score ≥ 10 or a weight reduction of ≥ 20%, was used as a criterion for euthanasia. The primary outcome was the survival rate (either no death or no need for euthanasia). The progression of disease was specified as M-CASS, body weight, blood glucose, histopathological changes to lung, liver, spleen, kidney, brain and heart tissues. Survival rate in I.P. LPS-20 mice was 0% (2/3 died; 1/3 euthanized with M-CASS > 10) at 24 h. Survival rate in all doses of I.N. LPS was 100% (20/20; 3–4 per group) at 96 h. 24 h mean M-CASS post-I.P. LPS-10 was 6.4/21 significantly higher than I.N. LPS-10 of 1.7/21 (Unpaired t test, P < 0.05). Organ injury was present at 96 h in the I.P. LPS-10 group: lung (3/3; 100%), spleen (3/3; 100%) and liver (1/3; 33%). At 24 h in the I.P. LPS-20 group, kidney injury was observed in the euthanized mouse. At 96 h in the post-I.N. LPS-20 group, only lung injury was observed in 2/3 (67%) mice (Kruskal-Wallis test with Dunn’s, P < 0.01). At 24 h in the post-I.N. LPS-100 group all (4/4) mice had evidence of lung injury. Variable doses of I.N. LPS in mice produced lung injury but did not produce sepsis. Higher doses of I.P. LPS induced multi-organ injury but not respiratory sepsis. Lethal models of respiratory virus, e.g., influenza A, might provide alternative avenues that can be explored in future research.

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Section: Main Textmentioning

confidence: 99%

Intraperitoneal versus intranasal administration of lipopolysaccharide in causing sepsis severity in a murine model: a preliminary comparison

Jiao,

Tong,

Zhao

et al. 2024

Lab Anim Res

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Ursodeoxycholic Acid‐Decorated Zwitterionic Nanoparticles for Orally Liver‐Targeted Close‐Looped Insulin Delivery

Ma,

Wang,

et al. 2024

Adv Healthcare Materials

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Oral insulin therapies targeting the liver and further simulating close‐looped secretion face significant challenges due to multiple trans‐epithelial barriers. Herein, we designed ursodeoxycholic acid (UDCA)‐decorated zwitterionic nanoparticles (UC‐CMs@ins) to overcome these barriers, target the liver, and respond to blood glycemia, thereby achieving oral one‐time‐per‐day therapy. UC‐CMs@ins showed excellent penetration of the intestinal mucus through the introduction of zwitterion (carboxy betaine, CB) introduction. Furthermore, UC‐CMs@ins possessed superior cellular internalization via proton‐assisted amino acid transporter 1 (PAT1, CB‐receptor) and apical sodium‐dependent bile acid transporter (ASBT, UDCA‐receptor) pathways. Moreover, UC‐CMs@ins exhibited excellent endolysosomal escape ability and improved the basolateral release of insulin into the bloodstream via the Golgi apparatus, ileal bile acid‐binding protein (IBABP), and the heteromeric organic solute transporter (OSTα‐ OSTβ) routes compared with non‐UDCA‐decorated C‐CMs@ins. Therefore, CB and UDCA jointly overcame mucus and intestinal barriers. Additionally, UC‐CMs@ins prevented insulin degradation in the gastrointestinal tract for crosslinked structure, improved insulin accumulation in the liver for UDCA introduction, and effectively regulated blood glucose for “closed‐loop” glucose control. Surprisingly, oral ingestion of UC‐CMs@ins showed a superior effect on blood glucose (∼ 22 h, normoglycemia), as well as improved postprandial glycemic levels (PGLs) in diabetic mice, illustrating the enormous potential of the prepared nanoparticles as a platform for oral insulin administration in diabetes treatment.This article is protected by copyright. All rights reserved

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Delivery of biologics: Topical administration

Kulchar,

Singh,

Ding

et al. 2023

Biomaterials

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Affordable oral proinsulin bioencapsulated in plant cells regulates blood sugar levels similar to natural insulin

Cited by 9 publications

References 87 publications

Intraperitoneal versus intranasal administration of lipopolysaccharide in causing sepsis severity in a murine model: a preliminary comparison

Intraperitoneal versus intranasal administration of lipopolysaccharide in causing sepsis severity in a murine model: a preliminary comparison

Ursodeoxycholic Acid‐Decorated Zwitterionic Nanoparticles for Orally Liver‐Targeted Close‐Looped Insulin Delivery

Delivery of biologics: Topical administration

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