Clinical Potential of VIP by Modified Pharmaco-kinetics and Delivery Mechanisms

Burian, Bernhard; Ortner, Anna; Ruth, Peter; Zimmer, Andreas; Mosgoeller, Wilhelm

doi:10.2174/187153012803832594

Cited by 10 publications

(5 citation statements)

References 67 publications

(82 reference statements)

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“…CGRP regulates inflammation and promotes epithelial repair [ 75 ]. Indeed, the current development of VIP-based bronchodilatory drugs that overcome VIP's short half-life indicates that the neuropeptide research remains an option [ 76 ].…”

Section: Discussionmentioning

confidence: 99%

Intratracheal Administration of Mesenchymal Stem Cells Modulates Tachykinin System, Suppresses Airway Remodeling and Reduces Airway Hyperresponsiveness in an Animal Model

et al. 2016

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BackgroundThe need for new options for chronic lung diseases promotes the research on stem cells for lung repair. Bone marrow-derived mesenchymal stem cells (MSCs) can modulate lung inflammation, but the data on cellular processes involved in early airway remodeling and the potential involvement of neuropeptides are scarce.ObjectivesTo elucidate the mechanisms by which local administration of MSCs interferes with pathophysiological features of airway hyperresponsiveness in an animal model.MethodsGFP-tagged mouse MSCs were intratracheally delivered in the ovalbumin mouse model with subsequent functional tests, the analysis of cytokine levels, neuropeptide expression and histological evaluation of MSCs fate and airway pathology. Additionally, MSCs were exposed to pro-inflammatory factors in vitro.ResultsFunctional improvement was observed after MSC administration. Although MSCs did not adopt lung cell phenotypes, cell therapy positively affected airway remodeling reducing the hyperplastic phase of the gain in bronchial smooth muscle mass, decreasing the proliferation of epithelium in which mucus metaplasia was also lowered. Decrease of interleukin-4, interleukin-5, interleukin-13 and increase of interleukin-10 in bronchoalveolar lavage was also observed. Exposed to pro-inflammatory cytokines, MSCs upregulated indoleamine 2,3-dioxygenase. Moreover, asthma-related in vivo upregulation of pro-inflammatory neurokinin 1 and neurokinin 2 receptors was counteracted by MSCs that also determined a partial restoration of VIP, a neuropeptide with anti-inflammatory properties.ConclusionIntratracheally administered MSCs positively modulate airway remodeling, reduce inflammation and improve function, demonstrating their ability to promote tissue homeostasis in the course of experimental allergic asthma. Because of a limited tissue retention, the functional impact of MSCs may be attributed to their immunomodulatory response combined with the interference of neuropeptide system activation and tissue remodeling.

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Section: Discussionmentioning

confidence: 99%

Intratracheal Administration of Mesenchymal Stem Cells Modulates Tachykinin System, Suppresses Airway Remodeling and Reduces Airway Hyperresponsiveness in an Animal Model

et al. 2016

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“…Nanoparticles, as sustained-release carriers, can slowly release VPAC2-selective agonists to maintain their effective concentration in patients and continually stimulate insulin secretion without causing hypotension and other potential side effects caused by current drug candidates, which are related to infusion rate and high dose ( 75 , 76 ). Nanoparticle conjugation with VPAC2-selective agonists can not only prolong the half-lives but can also facilitate a targeted drug delivery to improve drug efficacy ( 74 , 77 ). Selenium nanoparticles (SeNPs) have been proven to delay the progression of diabetes owing to their antioxidant properties ( 78 , 79 ).…”

Section: Application Of Nanoparticles On Vpac2-selective Agonistsmentioning

confidence: 99%

Therapeutic potential of vasoactive intestinal peptide and its receptor VPAC2 in type 2 diabetes

Hou

Yang²,

Yang³

et al. 2022

Front. Endocrinol.

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Owing to the increasing prevalence of type 2 diabetes, the development of novel hypoglycemic drugs has become a research hotspot, with the ultimate goal of developing therapeutic drugs that stimulate glucose-induced insulin secretion without inducing hypoglycemia. Vasoactive intestinal peptide (VIP), a 28-amino-acid peptide, can stimulate glucose-dependent insulin secretion, particularly by binding to VPAC2 receptors. VIP also promotes islet β-cell proliferation through the forkhead box M1 pathway, but the specific molecular mechanism remains to be studied. The clinical application of VIP is limited because of its short half-life and wide distribution in the human body. Based on the binding properties of VIP and VPAC2 receptors, VPAC2-selective agonists have been developed to serve as novel hypoglycemic drugs. This review summarizes the physiological significance of VIP in glucose homeostasis and the potential therapeutic value of VPAC2-selective agonists in type 2 diabetes.

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“…We selected studies via PubMed search and evaluated references identified in key reviews. 2,3,6,[13][14][15] To limit the scope to those with the greatest translational potential, we included only articles published within the last 10 years. Furthermore, we included only studies assessing nanoformulations in vivo, including 1 patient study (Table S2).…”

Section: Reviewmentioning

confidence: 99%

Nanoparticle-Based Therapies in Hypertension

Story,

Aminoroaya,

Skelton

et al. 2023

Hypertension

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Nearly 1.4 billion people worldwide suffer from arterial hypertension, a significant risk factor for cardiovascular disease which is now the leading cause of death. Despite numerous drugs designed to treat hypertension, only ≈14% of hypertensive individuals have their blood pressure under control. A critical factor negatively impacting the efficacy of available treatments is their poor bioavailability. This leads to increased dosing requirements which can result in more side effects, resulting in patient noncompliance. A recent solution to improve dosing and bioavailability issues has been to incorporate drugs into nanoparticle carriers, with over 50 nanodrugs currently on the market across all diseases, and another 51 currently in clinical trials. Given their ability to improve solubility and bioavailability, nanoparticles may offer significant advantages in the formulation of antihypertensives to overcome pharmacokinetic shortcomings. To date, however, no antihypertensive nanoformulations have been clinically approved. This review assesses in vivo study data from preclinical antihypertensive nanoformulation development and testing. Combined, the results of these studies suggest nanoformulation of antihypertensive drugs may be a promising solution to overcome the poor efficacy of currently available antihypertensives, and with further advances has the potential to open paths for new substances that have heretofore been clinically unrealistic due to poor bioavailability.

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Clinical Potential of VIP by Modified Pharmaco-kinetics and Delivery Mechanisms

Cited by 10 publications

References 67 publications

Intratracheal Administration of Mesenchymal Stem Cells Modulates Tachykinin System, Suppresses Airway Remodeling and Reduces Airway Hyperresponsiveness in an Animal Model

Intratracheal Administration of Mesenchymal Stem Cells Modulates Tachykinin System, Suppresses Airway Remodeling and Reduces Airway Hyperresponsiveness in an Animal Model

Therapeutic potential of vasoactive intestinal peptide and its receptor VPAC2 in type 2 diabetes

Nanoparticle-Based Therapies in Hypertension

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