Interactions of human secretin with sterically stabilized phospholipid micelles amplify peptide-induced vasodilation in vivo

Gandhi, Salil; Tsueshita, Takaya; Önyüksel, Hayat; Chandiwala, Rinku; Rubinstein, Israel

doi:10.1016/s0196-9781(02)00092-x

Cited by 15 publications

(5 citation statements)

References 18 publications

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“…We have observed that various amphipathic peptide drugs undergo spontaneous association with SSM in aqueous media [20,33,[75][76][77][78][79]. Peptides such as vasoactive intestinal peptide (VIP), glucagon-like peptide 1 [GLP-1(7-36)] and gastric inhibitory peptides, associate most probably with the PEG region of PEGylated micelles, in view of the molecular net charge and relative hydrophilicity/hydrophobicity of these peptide candidates, rather than the more hydrophobic micelle cores as demonstrated in our previous fluorescence emission spectroscopic studies [76].…”

Section: Delivery Of Peptide and Protein Drugsmentioning

confidence: 99%

“…When administered in vivo, SSM protects the associated peptides from plasma enzymes inactivation, bringing about enhanced and significantly prolonged biological activities (Fig. 3) [33,75,77,78]. Furthermore, specific peptide molecules undergo secondary conformational transition from random coil in aqueous media to show significantly increased α helicity in the presence of micelles.…”

Section: Delivery Of Peptide and Protein Drugsmentioning

confidence: 99%

See 1 more Smart Citation

Improvement of drug safety by the use of lipid-based nanocarriers

Lim

Banerjee

Önyüksel

2012

Journal of Controlled Release

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259

142

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Section: Delivery Of Peptide and Protein Drugsmentioning

confidence: 99%

Section: Delivery Of Peptide and Protein Drugsmentioning

confidence: 99%

Improvement of drug safety by the use of lipid-based nanocarriers

Lim

Banerjee

Önyüksel

2012

Journal of Controlled Release

Self Cite

259

142

View full text Add to dashboard Cite

“…The systemic hypertension in SCT −/− mice could be due to dysregulation of the RAAS with lowered VEGF and NO levels and higher aldosterone levels because of SCT deficiency. SCT could upregulate VEGF production in epithelial cells of the bile ducts 17 and exert coronary vasodilation via augmented endothelial release of NO 14,15,29 . Our results showed a significant reduction in plasma VEGF and NO levels in SCT −/− mice.…”

Section: Discussionmentioning

confidence: 99%

“…Secretin receptor (SCTR) transcripts were found to be highly expressed in both the heart and lungs 11,12 . In the heart, SCT is able to reduce blood pressure 13 , increase cardiac blood flow, regulate myocardial contraction and control coronary vasodilation through endothelial release of nitric oxide (NO) 14–16 . In the lungs, SCT can stimulate chloride (Cl − ) efflux from bronchial epithelial cells, which is important for airway surface liquid (ASL) and mucociliary clearance and tertiary bronchiole relaxation in humans 12 .…”

Section: Introductionmentioning

confidence: 99%

Loss of secretin results in systemic and pulmonary hypertension with cardiopulmonary pathologies in mice

Zaw

Sekar

Mak

et al. 2019

Sci Rep

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More than 1 billion people globally are suffering from hypertension, which is a long-term incurable medical condition that can further lead to dangerous complications and death if left untreated. In earlier studies, the brain-gut peptide secretin (SCT) was found to be able to control blood pressure by its cardiovascular and pulmonary effects. For example, serum SCT in patients with congestive heart failure was one-third of the normal level. These observations strongly suggest that SCT has a causal role in blood pressure control, and in this report, we used constitutive SCT knockout (SCT−/−) mice and control C57BL/6N mice to investigate differences in the morphology, function, underlying mechanisms and response to SCT treatment. We found that SCT−/− mice suffer from systemic and pulmonary hypertension with increased fibrosis in the lungs and heart. Small airway remodelling and pulmonary inflammation were also found in SCT−/− mice. Serum NO and VEGF levels were reduced and plasma aldosterone levels were increased in SCT−/− mice. Elevated cardiac aldosterone and decreased VEGF in the lungs were observed in the SCT−/− mice. More interestingly, SCT replacement in SCT−/− mice could prevent the development of heart and lung pathologies compared to the untreated group. Taken together, we comprehensively demonstrated the critical role of SCT in the cardiovascular and pulmonary systems and provide new insight into the potential role of SCT in the pathological development of cardiopulmonary and cardiovascular diseases.

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“…We have previously developed a proprietary long-acting, biocompatible and biodegradable drug delivery platform composed of distearoylphosphatidylethanolamine conjugated to polyethylene glycol of molecular weight 2000 Daltons (DSPE-PEG 2000 ) nanomicelles (SSM; hydrodynamic diameter, ~15 nm) and used it to stabilize and improve bioavailability of various amphipathic peptide drugs and water-insoluble drugs (8)(9)(10)(11)(12)(13). We found that above the critical micellar concentration (CMC; ~1.0 µM), ~90 monomers of DSPE-PEG 2000 self-assemble to form one SSM in aqueous media (14).…”

Section: Introductionmentioning

confidence: 99%