Insulin- and cholic acid-loaded zein/casein–dextran nanoparticles enhance the oral absorption and hypoglycemic effect of insulin

Bao, Xiaoyan; Qian, Kan; Yao, Ping

doi:10.1039/d1tb00806d

Cited by 46 publications

(33 citation statements)

References 54 publications

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“…In our work, the relative oral bioavailability of insulin formulated in PEG-coated nanoparticles was calculated to be close to 10%, 2.5-fold higher than for bare nanoparticles. This oral bioavailability is higher than other values previously published with PLGAchitosan composite nanocarriers (about 8%; [57]) or SNEDDS (about 1.8%; [58]); although, it is lower (about 2-times) when compared with other previous results obtained with liposomes decorated with PEG and folic acid (19.08%; [59]), folate-chitosan nanoparticles (17.04%; [60]), or zein/caseinate-based nanoparticles co-encapsulating insulin and cholic acid (20.5%; [61]). In spite of the lower capability to promote the oral absorption of insulin, our formulation offers some interesting advantages that may facilitate a translational approach; particularly in those aspects related to the scale-up of a reproducible process (including the drying step) and the simplification of non-clinical toxicity assessments of the regulatory dossier.…”

Section: Discussionmentioning

confidence: 60%

Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery

et al. 2021

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Zein, the major storage protein from corn, has a GRAS (Generally Regarded as Safe) status and may be easily transformed into nanoparticles, offering significant payloads for protein materials without affecting their stability. In this work, the capability of bare zein nanoparticles (mucoadhesive) and nanoparticles coated with poly(ethylene glycol) (mucus-permeating) was evaluated as oral carriers of insulin (I-NP and I-NP-PEG, respectively). Both nanocarriers displayed sizes of around 270 nm, insulin payloads close to 80 µg/mg and did not induce cytotoxic effects in Caco-2 and HT29-MTX cell lines. In Caenorhabditis elegans, where insulin decreases fat storage, I-NP-PEG induced a higher reduction in the fat content than I-NP and slightly lower than the control (Orlistat). In diabetic rats, nanoparticles induced a potent hypoglycemic effect and achieved an oral bioavailability of 4.2% for I-NP and 10.2% for I-NP-PEG. This superior effect observed for I-NP-PEG would be related to their capability to diffuse through the mucus layer and reach the surface of enterocytes (where insulin would be released), whereas the mucoadhesive I-NP would remain trapped in the mucus, far away from the absorptive epithelium. In summary, PEG-coated zein nanoparticles may be an interesting device for the effective delivery of proteins through the oral route.

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Section: Discussionmentioning

confidence: 60%

Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery

et al. 2021

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“…Combining a protective and mucoadhesive alginate layer with an octaarginine-based CPP for insulin delivery improved the reduction in blood glucose level following administration compared to controls . Similar enhancements to gastrointestinal insulin absorption have also been achieved with mucopenetrating coatings including dextran, hyaluronic acid, and polymeric N -(2-hydroxypropyl) methacrylamide. ,, However, the suitability and performance of these sacrificial mucopenetrating coatings for the resulting cellular uptake were shown to be highly dependent on the molecular weight and coating density of the mucopenetrating moiety. , Moreover, the mechanism of cellular uptake is influential as well, as there has been some evidence to suggest that nanoparticles reaching the gut epithelium possess a limiting concentration as the target uptake pathway becomes saturated . To overcome these limitations, other adjacent pathways, such as bile acid transporter mediated uptake or selective targeting of other components of the epithelium such as goblet cells, have both yielded improved in vivo bioavailability. , For example, zein/casein-dextran nanoparticles were formulated to coencapsulate insulin and cholic acid for transmucosal delivery to the intestine (Figure c) .…”

Section: Mucosae and Nanoparticle Designmentioning

confidence: 89%

Section: Mucosae and Nanoparticle Designmentioning

confidence: 99%

Untangling Mucosal Drug Delivery: Engineering, Designing, and Testing Nanoparticles to Overcome the Mucus Barrier

Watchorn

Clasky

Prakash

et al. 2022

ACS Biomater. Sci. Eng.

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Mucus is a complex viscoelastic gel and acts as a barrier covering much of the soft tissue in the human body. High vascularization and accessibility have motivated drug delivery to various mucosal surfaces; however, these benefits are hindered by the mucus layer. To overcome the mucus barrier, many nanomedicines have been developed, with the goal of improving the efficacy and bioavailability of drug payloads. Two major nanoparticle-based strategies have emerged to facilitate mucosal drug delivery, namely, mucoadhesion and mucopenetration. Generally, mucoadhesive nanoparticles promote interactions with mucus for immobilization and sustained drug release, whereas mucopenetrating nanoparticles diffuse through the mucus and enhance drug uptake. The choice of strategy depends on many factors pertaining to the structural and compositional characteristics of the target mucus and mucosa. While there have been promising results in preclinical studies, mucus−nanoparticle interactions remain poorly understood, thus limiting effective clinical translation. This article reviews nanomedicines designed with mucoadhesive or mucopenetrating properties for mucosal delivery, explores the influence of site-dependent physiological variation among mucosal surfaces on efficacy, transport, and bioavailability, and discusses the techniques and models used to investigate mucus−nanoparticle interactions. The effects of non-homeostatic perturbations on protein corona formation, mucus composition, and nanoparticle performance are discussed in the context of mucosal delivery. The complexity of the mucosal barrier necessitates consideration of the interplay between nanoparticle design, tissue-specific differences in mucus structure and composition, and homeostatic or disease-related changes to the mucus barrier to develop effective nanomedicines for mucosal delivery.

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“…More recent efforts have focused on co-administration of protease inhibitors or permeability modifiers with specialized carriers with only minor improvements in bioavailability (Bao et al, 2021). Other efforts have ignored the intestine altogether and explored protein and peptide delivery through transdermal patches containing microneedles (Aich et al, 2021) or inhalation of lyophilized therapeutic protein powders (Eedara et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Transenteric delivery of antibodies via an orally ingestible robotic pill yields high bioavailability comparable to parenteral administration in awake canines

Yamaguchi

Dam²,

Dhalla³

et al. 2022

Front. Drug. Deliv.

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Biotherapeutics such as peptides and antibodies are highly efficacious clinically but, unlike conventional medications, cannot be administered orally as they get digested and inactivated. Thus, biotherapeutics require parenteral routes for delivery, such as intravenous, intramuscular or subcutaneous administration. However, these delivery methods have limitations such as poor patient compliance or may require clinical supervision compared to oral therapies. We explored whether a novel, orally administered transenteric delivery system (Robotic Pill) could provide equivalent bioavailability to parenterally administered drugs. Utilizing an awake canine model, we demonstrated that orally administered Robotic Pills containing either human IgG or an anti-cytokine monoclonal antibody directed against either TNFα or interleukin-17A yielded bioavailability equivalent to parenterally administered controls. The ability to achieve clinically relevant blood levels of biotherapeutics via any orally administered preparation represents an important advance in drug delivery.

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Insulin- and cholic acid-loaded zein/casein–dextran nanoparticles enhance the oral absorption and hypoglycemic effect of insulin

Abstract: Diabetes mellitus is the most common metabolic disease in the world. Herein, insulin- and cholic acid-loaded zein nanoparticles with dextran surface were fabricated to enhance the oral absorptions of insulin...

Cited by 46 publications

References 54 publications

Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery

Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery

Untangling Mucosal Drug Delivery: Engineering, Designing, and Testing Nanoparticles to Overcome the Mucus Barrier

Transenteric delivery of antibodies via an orally ingestible robotic pill yields high bioavailability comparable to parenteral administration in awake canines

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