Potential Application of Intranasal Insulin Delivery for Treatment of Intracerebral Hemorrhage: A Review of The Literature

Javaid, Muhammad Ali; Selim, Magdy; Ortega‐Gutiérrez, Santiago; Lattanzi, Simona; Zargar, Shima; Alaouieh, Danielle; Hong, Emily; Divani, Afshin A.

doi:10.1016/j.jstrokecerebrovasdis.2022.106489

Cited by 3 publications

(1 citation statement)

References 128 publications

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“…Unlike the oral or intestinal route, it is devoid of extensive enzymatic degradation and hepatic first-pass metabolism of the administered drug [ 1 ]. In addition, a recent study suggests that intranasally administered insulin acts as a neuroprotective agent for ischemic stroke, subarachnoid hemorrhage and traumatic brain injury due to its ability to bypass the blood–brain barrier to distribute into the cerebrospinal fluid at a higher concentration [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Arginine-Coated Nanoglobules for the Nasal Delivery of Insulin

et al. 2023

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Multiple daily injections via subcutaneous route are the primary modes of insulin delivery for patients with Diabetes Mellitus. While this process is invasive, painful and may cause patients to develop lipohypertrophy at injection site, the perception of fear surrounding this process causes patients to delay in initiation and remain persistent with insulin therapy over time. Moreover, poor glycemic control may often lead to acute complications, such as severe hypoglycemia and nocturnal hypoglycemia, especially in older patients with diabetes. To address the imperative need for a patient-convenient non-invasive insulin therapy, an insulin-loaded arginine-coated self-emulsifying nanoglobule system (INS-LANano) was developed for nasal delivery of insulin with a biodegradable cationic surfactant—Lauroyl Ethyl Arginate (LAE). Incorporation of LAE resulted in formation of positively charged nanoglobules with L-arginine oriented on the surface. LANano enabled binding of insulin molecules on the surface of nanoglobules via an electrostatic interaction between negatively charged α-helix and LAE molecules at physiological pH. INS-LANano showed a hydrodynamic diameter of 23.38 nm with a surface charge of +0.118 mV. The binding efficiency of insulin on LANano globules was confirmed by zeta potential, circular dichroism (CD) spectroscopy and centrifugal ultrafiltration studies. The attachment of insulin with permeation-enhancing nanoglobules demonstrated significantly higher in vitro permeability of insulin of 15.2% compared to insulin solution across human airway epithelial cell (Calu-3) monolayer. Upon intranasal administration of INS-LANano to diabetic rats at 2 IU/kg insulin dose, a rapid absorption of insulin with significantly higher Cmax of 14.3 mU/L and relative bioavailability (BA) of 23.3% was observed. Therefore, the INS-LANano formulation significant translational potential for intranasal delivery of insulin

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Section: Introductionmentioning

confidence: 99%

Arginine-Coated Nanoglobules for the Nasal Delivery of Insulin

et al. 2023

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Improving outcomes in intracerebral hemorrhage through microglia/macrophage-targeted IL-10 delivery with phosphatidylserine liposomes

et al. 2023

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Recent Advances in Drug Delivery Systems Targeting Insulin Signalling for the Treatment of Alzheimer’s Disease

Sachdeva,

Narayanan,

Sinha

et al. 2024

JAD

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Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by the accumulation of neurofibrillary tangles and amyloid-β plaques. Recent research has unveiled the pivotal role of insulin signaling dysfunction in the pathogenesis of AD. Insulin, once thought to be unrelated to brain function, has emerged as a crucial factor in neuronal survival, synaptic plasticity, and cognitive processes. Insulin and the downstream insulin signaling molecules are found mainly in the hippocampus and cortex. Some molecules responsible for dysfunction in insulin signaling are GSK-3β, Akt, PI3K, and IRS. Irregularities in insulin signaling or insulin resistance may arise from changes in the phosphorylation levels of key molecules, which can be influenced by both stimulation and inactivity. This, in turn, is believed to be a crucial factor contributing to the development of AD, which is characterized by oxidative stress, neuroinflammation, and other pathological hallmarks. Furthermore, this route is known to be indirectly influenced by Nrf2, NF-κB, and the caspases. This mini-review delves into the intricate relationship between insulin signaling and AD, exploring how disruptions in this pathway contribute to disease progression. Moreover, we examine recent advances in drug delivery systems designed to target insulin signaling for AD treatment. From oral insulin delivery to innovative nanoparticle approaches and intranasal administration, these strategies hold promise in mitigating the impact of insulin resistance on AD. This review consolidates current knowledge to shed light on the potential of these interventions as targeted therapeutic options for AD.

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Potential Application of Intranasal Insulin Delivery for Treatment of Intracerebral Hemorrhage: A Review of The Literature

Cited by 3 publications

References 128 publications

Arginine-Coated Nanoglobules for the Nasal Delivery of Insulin

Arginine-Coated Nanoglobules for the Nasal Delivery of Insulin

Improving outcomes in intracerebral hemorrhage through microglia/macrophage-targeted IL-10 delivery with phosphatidylserine liposomes

Recent Advances in Drug Delivery Systems Targeting Insulin Signalling for the Treatment of Alzheimer’s Disease

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