Cholesterol moieties as building blocks for assembling nanoparticles to achieve effective oral delivery of insulin

Ding, Yu An; Wang, Qiaochu; Liu, Guangqu; Feng, Yechen

doi:10.1039/d0bm00577k

Cited by 9 publications

(10 citation statements)

References 59 publications

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“…This can alter the nanoparticle physicochemical attributes, such as size, shape, zeta potential, surface morphology and hydrophobicity, leading to particle aggregation/agglomeration, altered enzymatic metabolism, reduced intestinal mucus-mucosa transit, lower binding affinity for cellular receptor or membrane, and poorer target cellular uptake and translocation. In vitro analysis of intestinal receptor-mediated nanoinsulin indicates that generally less than 40% of insulin may be released in the intestinal tract over a few hours of incubation [43,103,131,132,134,136,141,148]. The in vivo insulin release profiles of nanoparticles nonetheless may be further reduced by the surface-adsorbed proteins and nutrients.…”

Section: Discussionmentioning

confidence: 99%

Critical material designs for mucus- and mucosa-penetrating oral insulin nanoparticle development

Zaiki

Lim

Wong

2022

International Materials Reviews

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Subcutaneous and pulmonary insulin is associated with medical and pharmaceutical complications. Oral insulin mimics physiological glucose regulation with reduced hypoglycemia and coma risks. Nanoparticles are advocated as oral insulin carrier to overcome intestinal absorption barrier. Their insulin bioavailability and blood glucose lowering performances are hampered by inefficient mucus and mucosa transport of nanoparticles. This review discusses critical materials used in oral insulin nanoparticle design to address mucus and mucosa penetrating hurdles. It highlights intestinal receptor targeting, biomimetic virus mimicking, particulate surface charge switching, coat-core detachment, and combination approaches developed through material sciences. Mucus penetration favors particles with hydrophilic/amphiphilic surfaces with no net charges. Mucosa penetration shows a preponderance for hydrophobic or positively charged surfaces with intestinal receptor binding affinity. Materials with switchable physicochemical properties along with mucus-mucosa transit require research exploration, with consideration of their influences on endocytosis, lysosomal escape, exocytosis, and intestinal receptor upregulation.

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Section: Discussionmentioning

confidence: 99%

Critical material designs for mucus- and mucosa-penetrating oral insulin nanoparticle development

Zaiki

Lim

Wong

2022

International Materials Reviews

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“…For in vitro enzymatic degradation, protection ability of HCP and CNP against the enzymatic degradation of insulin was investigated according to the previous report. [ 39 ] NPs were incubated with pepsin (pH = 1.2, 125 IU mL −1 ) or trypsin (pH = 6.8, 250 IU mL −1 ) at 37 °C under stirring. At different time intervals, quantitative aliquots of sample were collected.…”

Section: Methodsmentioning

confidence: 99%

Hyaluronic‐Acid‐Coated Chitosan Nanoparticles for Insulin Oral Delivery: Fabrication, Characterization, and Hypoglycemic Ability

Guo

Nan

et al. 2022

Macromolecular Bioscience

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Oral administration of insulin faces multiple biological challenges, such as varied digestive environments, mucin exclusion, and low epithelial cells’ absorption. In the present study, a hyaluronic acid (HA)‐coated chitosan (CS) nanoparticle (HCP) delivery system is fabricated for insulin oral delivery. It is hypothesized that the developed nanoparticles will protect insulin from digestive degradation, promote intestinal epithelial cell absorption, and exert strong in vivo hyperglycemic ability. Nanoparticles formulated by CS and sodium tripolyphosphate (TPP) are optimized to form the core nanoparticles (CNPs). HA is further applied to coat CNP (HCP) to improve stability, reduce enzymatic degradation, and promote absorption of insulin. HCP promotes insulin uptake by Caco‐2 cells, absorbs less mucin, and improves intestinal absorption. Moreover, an in vivo test demonstrates that oral administration of insulin‐loaded HCP exerts strong and continuous hyperthermia effect (with a pharmacological availability (PA) of 13.8%). In summary, HCP is a promising delivery platform for insulin oral administration in terms of protecting insulin during digestion, facilitating its absorption and ultimately promoting its oral bioavailability.

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“…The diabetic rat (male Sprague-Dawley rat) model was established by streptozotocin administration according to a previously described method [36,37]. Fasting BGLs were measured using a blood glucose meter (5DM-2A, Yicheng Biotech.…”

Section: In Vivo Studies For Type 1 Diabetes Treatmentmentioning

confidence: 99%

Multivesicular Liposomes for Glucose-Responsive Insulin Delivery

Liu

Ding

et al. 2021

Pharmaceutics

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An intelligent insulin delivery system is highly desirable for diabetes management. Herein, we developed a novel glucose-responsive multivesicular liposome (MVL) for self-regulated insulin delivery using the double emulsion method. Glucose-responsive MVLs could effectively regulate insulin release in response to fluctuating glucose concentrations in vitro. Notably, in situ released glucose oxidase catalyzed glucose enrichment on the MVL surface, based on the combination of (3-fluoro-4-((octyloxy)carbonyl)phenyl)boronic acid and glucose. The outer MVL membrane was destroyed when triggered by the local acidic and H2O2-enriched microenvironment induced by glucose oxidase catalysis in situ, followed by the further release of entrapped insulin. Moreover, the Alizarin red probe and molecular docking were used to clarify the glucose-responsive mechanism of MVLs. Utilizing chemically induced type 1 diabetic rats, we demonstrated that the glucose-responsive MVLs could effectively regulate blood glucose levels within a normal range. Our findings suggest that glucose-responsive MVLs with good biocompatibility may have promising applications in diabetes treatment.

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Cholesterol moieties as building blocks for assembling nanoparticles to achieve effective oral delivery of insulin

Abstract: The amphiphilic cholesterol-phosphate conjugate can fabricate into cholesterol-coated nanoparticles by reverse emulsion method. The nanoparticles generated a rapid-onset and long-lasting hypoglycemic effect following gavage in T1DM rats.

Cited by 9 publications

References 59 publications

Critical material designs for mucus- and mucosa-penetrating oral insulin nanoparticle development

Critical material designs for mucus- and mucosa-penetrating oral insulin nanoparticle development

Hyaluronic‐Acid‐Coated Chitosan Nanoparticles for Insulin Oral Delivery: Fabrication, Characterization, and Hypoglycemic Ability

Multivesicular Liposomes for Glucose-Responsive Insulin Delivery

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