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Glucose-Responsive Polyelectrolyte Complexes Based on Dendritic Mesoporous Silica for Oral Insulin Delivery

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Abstract

The postprandial glycemic regulation is essential for diabetic patients to reduce the risk of long-term microvascular and macrovascular complications. Herein, we designed a glucose-responsive oral insulin delivery system based on polyelectrolyte complexes (PECs) for controlling the increasing postprandial glucose concentrations. Briefly, alginate-g-3-aminophenylboronic acid (ALG-g-APBA) and chitosan-g-3-fluoro-4-carboxyphenylboronic acid (CS-g-FPBA) were wrapped on mesoporous silica (MSN) to form the negative charged ALG-g-APBA@MSN and the positive charged CS-g-FPBA@MSN nanoparticles, with an optimum insulin loading capacity of 124 mg/g and 295 mg/g, respectively. ALG-g-APBA@MSN was further cross-linked with CS-g-FPBA@MSN to form PECs through electrostatic interaction and borate esters. The dense polyelectrolyte network wrapped on MSN was capable of preventing insulin from diffusion and regulating its release. The in vitro insulin release of PECs demonstrated an obvious glucose response profile in different glucose concentrations (0 mg/mL, 2 mg/mL, 5 mg/mL) and presented a switch “on” and “off” release regulation at hyperglycemic or normal state. The CCK-8 assay showed that none of the MSN, ALG-g-APBA@MSN, CS-g-FPBA@MSN, and PECs possessed cytotoxicity to Caco-2 cells. For in vivo tests, the oral PECs exhibited a significant hypoglycemic effect and maintained in the euglycemic levels up to approximately 12 h on diabetic rats. Overall, the PECs directly triggered by postprandial glucose in the intestine have a good potential to be applied in intelligent insulin delivery by the oral route.

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Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China under Grant [number 81373365] and Guangdong Science and Technology Project under Grant [number 2015A010105014].

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Authors and Affiliations

  1. Biomaterial Research Center, School of Pharmaceutical Sciences, Southern Medical University, 1023 Southern Shatai Street, Guangzhou, 510515, China

    Tingting Qin, Libiao Yan, Siqi Lin & Qingbing Zeng

  2. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, 1023 Southern Shatai Street, Guangzhou, 510515, China

    Tingting Qin, Libiao Yan, Xin Wang, Siqi Lin & Qingbing Zeng

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  1. Tingting Qin
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Correspondence to Qingbing Zeng.

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Qin, T., Yan, L., Wang, X. et al. Glucose-Responsive Polyelectrolyte Complexes Based on Dendritic Mesoporous Silica for Oral Insulin Delivery. AAPS PharmSciTech 22, 226 (2021). https://doi.org/10.1208/s12249-021-02088-6

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