Dual crosslinking of folic acid-modified pectin nanoparticles for enhanced oral insulin delivery

Zhang, Fenglei; Pei, Xuejing; Peng, Xiaoxia; Gou, Dongxia; Fan, Xuetong; Zheng, Xiaotong; Song, Chengcheng; Zhou, Yifa; Cui, Sisi

doi:10.1016/j.bioadv.2022.212746

Cited by 19 publications

(11 citation statements)

References 34 publications

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“…As shown in Figure 6 A, free insulin was rapidly degraded in SGF (pH 1.2), with 34.07% free insulin remaining after 10 min; 1.17% free insulin remaining after 30 min; and after 60 min, the peak of insulin was no longer detected. The results indicated that free insulin was highly susceptible to degradation by pepsin, which was consistent with those reported in the literature [ 41 ]. In contrast, the insulin encapsulated in INs-STI-CS nanoparticles remained at 84.64% after 10 min and at 75.53% after 120 min.…”

Section: Resultssupporting

confidence: 92%

Insulin-Loaded Soybean Trypsin Inhibitor-Chitosan Nanoparticles: Preparation, Characterization, and Protective Effect Evaluation

et al. 2023

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The aim of this work was to prepare insulin-loaded nanoparticles using soybean trypsin inhibitor (STI) and chitosan (CS) as a potential coating. The nanoparticles were prepared by complex coacervation, and characterized for their particle size, polydispersity index (PDI), and encapsulation efficiency. In addition, the insulin release and enzymatic degradation of nanoparticles in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were evaluated. The results showed that the optimal conditions for preparing insulin-loaded soybean trypsin inhibitor-chitosan (INs-STI-CS) nanoparticles were as follows: CS concentration of 2.0 mg/mL, STI concentration of 1.0 mg/mL, and pH 6.0. The INs-STI-CS nanoparticles prepared at this condition had a high insulin encapsulation efficiency of 85.07%, the particle diameter size was 350 ± 5 nm, and the PDI value was 0.13. The results of the in vitro evaluation of simulated gastrointestinal digestion showed that the prepared nanoparticles could improve the stability of insulin in the gastrointestinal tract. Compared with free insulin, the insulin loaded in INs-STI-CS nanoparticles was retained at 27.71% after 10 h of digestion in the intestinal tract, while free insulin was completely digested. These findings will provide a theoretical basis for improving the stability of oral insulin in the gastrointestinal tract.

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Section: Resultssupporting

confidence: 92%

Insulin-Loaded Soybean Trypsin Inhibitor-Chitosan Nanoparticles: Preparation, Characterization, and Protective Effect Evaluation

et al. 2023

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“…The bioavailability of insulin is found to be improved with folic-acid-dependent cellular uptake. 121 Similarly, virus-mimicking nanoparticles were designed with folic acid by Cheng et al for oral insulin delivery; confocal microscopy showed that the nanoparticles were transported through folic-acid-mediated endocytosis. 122 Val-Leu-Pro-Val-Pro (VLPVP), a peptide drug for hypertension, was encapsulated in a PLGA and folic acid lipid shell to prevent the drug from gastric digestion.…”

Section: Nanoparticle Uptake: Taking Advantage Of Receptor-mediated E...mentioning

confidence: 99%

“…Zhang et al recently evaluated folic-acid-modified pectin nanoparticles for the oral delivery of insulin. The bioavailability of insulin is found to be improved with folic-acid-dependent cellular uptake . Similarly, virus-mimicking nanoparticles were designed with folic acid by Cheng et al for oral insulin delivery; confocal microscopy showed that the nanoparticles were transported through folic-acid-mediated endocytosis .…”

Section: Nanoparticle Uptake: Taking Advantage Of Receptor-mediated E...mentioning

confidence: 99%

Mechanisms of Nanoparticle Transport across Intestinal Tissue: An Oral Delivery Perspective

2023

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Oral drug administration has been a popular choice due to patient compliance and limited clinical resources. Orally delivered drugs must circumvent the harsh gastrointestinal (GI) environment to effectively enter the systemic circulation.The GI tract has a number of structural and physiological barriers that limit drug bioavailability including mucus, the tightly regulated epithelial layer, immune cells, and associated vasculature. Nanoparticles have been used to enhance oral bioavailability of drugs, as they can act as a shield to the harsh GI environment and prevent early degradation while also increasing uptake and transport of drugs across the intestinal epithelium. Evidence suggests that different nanoparticle formulations may be transported via different intracellular mechanisms to cross the intestinal epithelium. Despite the existence of a significant body of work on intestinal transport of nanoparticles, many key questions remain: What causes the poor bioavailability of the oral drugs? What factors contribute to the ability of a nanoparticle to cross different intestinal barriers? Do nanoparticle properties such as size and charge influence the type of endocytic pathways taken? In this Review, we summarize the different components of intestinal barriers and the types of nanoparticles developed for oral delivery. In particular, we focus on the various intracellular pathways used in nanoparticle internalization and nanoparticle or cargo translocation across the epithelium. Understanding the gut barrier, nanoparticle characteristics, and transport pathways may lead to the development of more therapeutically useful nanoparticles as drug carriers.

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“…The beads were incubated at 37 °C under moderate stirring in both media. The enzymatic reaction was stopped with an equivalent volume of ice-cold reagent (0.1 M NaOH for SGF and 0.1 M HCl for SIF) [ 36 ]. The samples were analyzed using the Bradford assay.…”

Section: Methodsmentioning

confidence: 99%

Formulation and Evaluation of Insulin-Loaded Sodium-Alginate Microparticles for Oral Administration

Bácskay,

Papp,

Pártos

et al. 2023

Pharmaceutics

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The development of oral insulin drug delivery systems is still an ongoing challenge for pharmaceutical technology researchers, as the formulation process has to overcome a number of obstacles due to the adverse characteristics of peptides. The aim of this study was to formulate different sodium-alginate microparticles as a possible method for oral insulin administration. In our previous studies, the method has been successfully optimized using a small model peptide. The incorporation of insulin into alginate carriers containing nonionic surfactants has not been described yet. In order to enhance the absorption of insulin through biological barriers, Labrasol ALF and Labrafil M 2125 CS were selected as permeation-enhancing excipients. They were applied at a concentration of 0.10% (v/v%), along with various combinations of the two, to increase oral bioavailability. Encapsulation efficiency showed sufficient drug incorporation, as it resulted in over 80% in each composition. In vitro dissolution and enzymatic stability test results proved that, as a pH-responsive polymer, alginate bead swelling and drug release occur at higher pH, thus protecting insulin against the harsh environment of the gastrointestinal tract. The remaining insulin content was 66% due to SIF degradation after 120 min. Permeability experiments revealed the impact of permeation enhancers and natural polymers on drug absorption, as they enhanced drug transport significantly through Caco-2 cells in the case of alginate microparticle formulations, as opposed to the control insulin solution. These results suggest that these formulations are able to improve the oral bioavailability of insulin.

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Dual crosslinking of folic acid-modified pectin nanoparticles for enhanced oral insulin delivery

Cited by 19 publications

References 34 publications

Insulin-Loaded Soybean Trypsin Inhibitor-Chitosan Nanoparticles: Preparation, Characterization, and Protective Effect Evaluation

Insulin-Loaded Soybean Trypsin Inhibitor-Chitosan Nanoparticles: Preparation, Characterization, and Protective Effect Evaluation

Mechanisms of Nanoparticle Transport across Intestinal Tissue: An Oral Delivery Perspective

Formulation and Evaluation of Insulin-Loaded Sodium-Alginate Microparticles for Oral Administration

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