Enhancing insulin oral absorption by using mucoadhesive nanoparticles loaded with LMWP-linked insulin conjugates

Sheng, Jianyong; He, Huining; Han, Limei; Qin, Jing; Chen, Sunhui; Ru, Ge; Li, Ruixiang; Yang, Pei; Wang, Jianxin; Yang, Victor C.

doi:10.1016/j.jconrel.2016.05.015

Cited by 131 publications

(59 citation statements)

References 42 publications

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“…For decades, oral insulin delivery has been studied in humans and different experimental models (Murlin et al 1940, Florence 2015, Sheng et al 2016. Although the peptide insulin is destroyed in acid environment of stomach, by not completely understood means it promotes serum metabolic parameters improvement as well as promotes function and morphological changes in gut epithelium (Sukhotnik et al 2011, Shehadeh et al 2006.…”

Section: Introductionmentioning

confidence: 99%

Oral insulin improves metabolic parameters in high fat diet fed rats

Lipinski

Kmetiuk

Mathias

et al. 2017

An. Acad. Bras. Ciênc.

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Introduction/Aim: The gut has shown to have a pivotal role on the pathophysiology of metabolic disease. Food stimulation of distal intestinal segments promotes enterohormones secretion influencing insulin metabolism. In diabetic rats, oral insulin has potential to change intestinal epithelium behavior. This macromolecule promotes positive effects on laboratorial metabolic parameters and decreases diabetic intestinal hypertrophy. This study aims to test if oral insulin can influence metabolic parameters and intestinal weight in obese non-diabetic rats. Methods: Twelve weeks old Wistar rats were divided in 3 groups: control (CTRL) standard chow group; high fat diet low carbohydrates group (HFD) and HFD plus daily oral 20U insulin gavage (HFD+INS). Weight and food consumption were weekly obtained. After eight weeks, fasting blood samples were collected for laboratorial analysis. After euthanasia gut samples were isolated. Results: Rat oral insulin treatment decreased body weight gain (p<0,001), fasting glucose and triglycerides serum levels (p<0,05) an increased intestinal weight of distal ileum (P<0,05). Animal submitted to high fat diet presented higher levels of HOMA-IR although significant difference to CT was not achieved. HOMA-beta were significantly higher (p<0.05) in HFD+INS. Visceral fat was 10% lower in HFD+INS but the difference was not significant. Conclusions: In non-diabetic obese rats, oral insulin improves metabolic malfunction associated to rescue of beta-cell activity.

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Section: Introductionmentioning

confidence: 99%

Oral insulin improves metabolic parameters in high fat diet fed rats

Lipinski

Kmetiuk

Mathias

et al. 2017

An. Acad. Bras. Ciênc.

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“…There are also other ways to delivery macromolecules, such as by mechanoporation, where pores are formed to enable access [116]. A common strategy is the conjugation of macromolecules to mucoadhesive polymers, such as chitosan, to open TJs and facilitate paracellular transport [117].…”

Section: Macromoleculesmentioning

confidence: 99%

Strategies for the enhanced intracellular delivery of nanomaterials

Azevedo

Macedo

Sarmento

2018

Drug Discovery Today

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The intracellular delivery of nanomaterials and drugs has been attracting increasing research interest, mainly because of their important effects and functions in several organelles. Targeting specific organelles can help treat or decrease the symptoms of diabetes, cancer, infectious, and autoimmune diseases. Tuning biological and chemical properties enables the creation of functionalized nanomaterials with enhanced intracellular uptake, ability to escape premature lysosome degradation, and to reach a specific target. Here, we provide an update of recent advances in the intracellular delivery mechanisms that could help drugs reach their target more efficiently.

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“…Unlike native gelonin that could not enter cells to exert its cytotoxic effects, significant inhibition on tumor growth was observed in mice treated with CPP-Gel or rGel; suggesting that incorporation of CPP would dramatically enhance the cytotoxic activity of gelonin. On a different application, we also reported the formulation of homogenous, monomeric (1:1 ratio) LMWP-insulin covalent conjugate, which was capable of crossing the intestinal mucosal barrier, significantly augmenting the anti-diabetic effects of insulin [41,69,70]. …”

Section: Cell Penetrating Peptides (Cpps)-assisted Strategies For mentioning

confidence: 99%

CPP-Assisted Intracellular Drug Delivery, What Is Next?

Liu

et al. 2016

IJMS

Self Cite

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For the past 20 years, we have witnessed an unprecedented and, indeed, rather miraculous event of how cell-penetrating peptides (CPPs), the naturally originated penetrating enhancers, help overcome the membrane barrier that has hindered the access of bio-macromolecular compounds such as genes and proteins into cells, thereby denying their clinical potential to become potent anti-cancer drugs. By taking the advantage of the unique cell-translocation property of these short peptides, various payloads of proteins, nucleic acids, or even nanoparticle-based carriers were delivered into all cell types with unparalleled efficiency. However, non-specific CPP-mediated cell penetration into normal tissues can lead to widespread organ distribution of the payloads, thereby reducing the therapeutic efficacy of the drug and at the same time increasing the drug-induced toxic effects. In view of these challenges, we present herein a review of the new designs of CPP-linked vehicles and strategies to achieve highly effective yet less toxic chemotherapy in combating tumor oncology.

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Enhancing insulin oral absorption by using mucoadhesive nanoparticles loaded with LMWP-linked insulin conjugates

Cited by 131 publications

References 42 publications

Oral insulin improves metabolic parameters in high fat diet fed rats

Oral insulin improves metabolic parameters in high fat diet fed rats

Strategies for the enhanced intracellular delivery of nanomaterials

CPP-Assisted Intracellular Drug Delivery, What Is Next?

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