Intranasal delivery of insulin by self-emulsified nanoemulsion system: In vitro and in vivo studies

Shah, Darshana; Guo, Yuxing; Ban, Igor; Shao, Jun

doi:10.1016/j.ijpharm.2022.121565

Cited by 10 publications

(6 citation statements)

References 26 publications

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“…The binding of insulin with LANano globules was also evident from the comparatively lower recovery of insulin in the receiver chamber from INS-LANano than that of INS-SEN. The centrifugal ultrafiltration method was previously used by Darshana et al to determine the complexation of insulin with phosphatidylcholine and the consequent entrapment of insulin in preconcentrate globules [ 24 ]. The intranasal aqueous formulation contains a preservative for its long-term storage.…”

Section: Discussionmentioning

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: Discussionmentioning

confidence: 99%

Arginine-Coated Nanoglobules for the Nasal Delivery of Insulin

et al. 2023

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“… The emulsion (IN) showed the highest glucose reduction level and AUC. [ 48 ] Huperzine A (AD) Isopropyl myristate, Capryol 90, Cremophor EL, and Labrasol PS 15.24 nm, PDI 0.128, and ZP −4.48 mV Lactoferrin was modulated to enhance the brain-targeted efficiency through receptor-mediated transcytosis. The DTE of the nanoemulsion (IN) was 320%.…”

Section: Strategies To Improve Drug Delivery Via the Intranasal Routementioning

confidence: 99%

Recent Advances in Intranasal Administration for Brain-Targeting Delivery: A Comprehensive Review of Lipid-Based Nanoparticles and Stimuli-Responsive Gel Formulations

Koo,

Lim,

2024

IJN

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Addressing disorders related to the central nervous system (CNS) remains a complex challenge because of the presence of the blood-brain barrier (BBB), which restricts the entry of external substances into the brain tissue. Consequently, finding ways to overcome the limited therapeutic effect imposed by the BBB has become a central goal in advancing delivery systems targeted to the brain. In this context, the intranasal route has emerged as a promising solution for delivering treatments directly from the nose to the brain through the olfactory and trigeminal nerve pathways and thus, bypassing the BBB. The use of lipid-based nanoparticles, including nano/microemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers, has shown promise in enhancing the efficiency of nose-to-brain delivery. These nanoparticles facilitate drug absorption from the nasal membrane. Additionally, the in situ gel (ISG) system has gained attention owing to its ability to extend the retention time of administered formulations within the nasal cavity. When combined with lipid-based nanoparticles, the ISG system creates a synergistic effect, further enhancing the overall effectiveness of brain-targeted delivery strategies. This comprehensive review provides a thorough investigation of intranasal administration. It delves into the strengths and limitations of this specific delivery route by considering the anatomical complexities and influential factors that play a role during dosing. Furthermore, this study introduces strategic approaches for incorporating nanoparticles and ISG delivery within the framework of intranasal applications. Finally, the review provides recent information on approved products and the clinical trial status of products related to intranasal administration, along with the inclusion of quality-by-design–related insights.

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“…As we all know, the secondary structure of protein is easily damaged by external condition. CD spectroscopy is an effective method for detecting the structural integrity of proteins [13]. The CD spectra of insulin in different formulations are illustrated in Fig.…”

Section: Characterization Of Npsmentioning

confidence: 99%

“…In order to solve the above problems, nanocarriers have been proposed [7]. These nanocarriers include nanoliposomes [8,9], nanoemulsions [10][11][12][13], nanogel [14,15] and nanoparticles (NPs) [16][17][18][19]. Nevertheless, because of low loading capacity, high-cost, lack of stability, inferior biocompatibility, or bio-safety, many carriers still show some disadvantages in oral insulin delivery [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Keratin-based Nanoparticles for Oral Delivery of Insulin

Wang,

Song,

Xue

et al. 2024

Preprint

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Successful oral insulin administration can considerably enhance the quality of life (QOL) of diabetes patients who must frequently take insulin injections. Oral insulin administration, on the other hand, is seriously hampered by gastrointestinal enzymes, wide pH range, mucus, and mucosal layers, which limits insulin oral bioavailability to ≤ 2%. Herein, we prepared a simple, inexpensive and safe keratin-based nanoparticles (NPs) to encapsulate sufficient insulin to realize highly efficient oral insulin delivery. The optimized NPs (β-CD-K-IN-DG) achieved high insulin loading (encapsulation efficiency (98.52%) and loading capacity (32.81%)) while protecting insulin from acid and enzymatic degradation. In vivo results confirm that β-CD-K-IN-DG prolonged the residence time of insulin and controlled insulin release under physiological conditions, leading to a notable hypoglycemic effect and a high oral bioavailability of 12.27%. Our work demonstrates that keratin-based NPs can protect insulin from the gastric environment and overcome the intestinal barrier, thus providing the possibility for oral insulin delivery.

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Intranasal delivery of insulin by self-emulsified nanoemulsion system: In vitro and in vivo studies

Cited by 10 publications

References 26 publications

Arginine-Coated Nanoglobules for the Nasal Delivery of Insulin

Arginine-Coated Nanoglobules for the Nasal Delivery of Insulin

Recent Advances in Intranasal Administration for Brain-Targeting Delivery: A Comprehensive Review of Lipid-Based Nanoparticles and Stimuli-Responsive Gel Formulations

Keratin-based Nanoparticles for Oral Delivery of Insulin

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